Found 20 Presentations For Request "LBA1"

Poster Discussion 1 – Translational research Poster Discussion session

LBA16 - TCR-beta repertoire convergence and evenness are associated with response to immune checkpoint inhibitors (ID 5435)

Presentation Number
LBA16
Lecture Time
08:45 - 08:45
Speakers
  • Philip Jermann (Basel, Switzerland)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
08:45 - 09:45

Abstract

Background

Immune checkpoint inhibitors (ICI) significantly improve clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. However, as only a subset of patients responds to treatment, there is an urgent need for predictive biomarkers. Here we investigated the association of TCR-beta (TCRB) clonal expansion and convergence with treatment response. We assessed these features within the tumor microenvironment of treatment naïve patients and compared their predictive value with other biomarkers such as tumor mutational burden (TMB) and PD-L1 status.

Methods

Total RNA was extracted from NSCLC FFPE pretreatment tissue biopsies of patients receiving ICI therapy (n = 45). TCRB repertoire NGS libraries were prepared with the Oncomine TCRB-SR assay and sequenced on the Ion Torrent instrument. TCR convergence (=frequency of clonotypes identical in amino acid but different in nucleotide space) and clonal evenness (=measurement of the similarity of clone sizes) were evaluated independently using Fisher’s test. TMB values from the same biopsies were assessed from extracted genomic DNA via the Oncomine Tumor Mutation Load Assay. PD-L1 status was determined by immunohistochemical staining.

Results

Durable clinical benefit from ICI therapy was associated with increased TCR convergence (p = 0.12) and decreased clonal evenness (p = 0.01) independently. The TCR-based patient classification was able to identify responders who otherwise had low to intermediate (<9 Mutations per Mb) TMB or negative (<1%) PD-L1 status. Adding TCR evenness to TMB and PD-L1-based stratification allowed for the identification of 82% of responders, compared to 47% for TMB alone and to the identification of 94% of responders, compared to 59% for PD-L1 alone.

Conclusions

Our results show that evaluation of the TCR-beta repertoire in NSCLC specimens is an effective tool to stratify patients according to their response to ICI therapy. In particular, TCR assessment identifies subpopulations of responding patients that would otherwise be misclassified by either TMB or PD-L1 status. Thus, combinatorial use of several biomarkers may yield the highest clinical accuracy for ICI therapy selection.

Legal entity responsible for the study

Philip Jermann.

Funding

Thermo Fisher Scientific.

Disclosure

P. Jermann: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Thermo Fisher Scientific; Research grant / Funding (institution): BMS. K. Leonards: Research grant / Funding (institution): Thermo Fisher Scientific; Research grant / Funding (institution): Bristol-Myers Squibb. T. Looney: Full / Part-time employment: Thermo Fisher Scientific. I. Alborelli: Research grant / Funding (institution), Travel / Accommodation / Expenses: Thermo Fisher Scientific; Research grant / Funding (institution): Bristol-Myers Squibb. S.I. Rothschild: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck Serono; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis. S. Savic Prince: Honoraria (self), Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Honoraria (self): Roche. A. Zippelius: Advisory / Consultancy: BMS; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: NBE Therapeutics; Research grant / Funding (institution): Secarna; Research grant / Funding (institution): Beyondsprings; Research grant / Funding (institution): Crescendo; Research grant / Funding (institution): Hookipa. L. Bubendorf: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): BMS; Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.

Collapse
Presidential Symposium III Proffered Paper session

Invited Discussant LBA14_PR (ID 7287)

Lecture Time
18:05 - 18:15
Speakers
  • Thomas B. Powles (London, United Kingdom)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
16:30 - 18:15
Proffered Paper – Translational research Proffered Paper session

LBA15_PR - A phase III trial of empiric chemotherapy with cisplatin and gemcitabine or systemic treatment tailored by molecular gene expression analysis in patients with carcinomas of an unknown primary (CUP) site (GEFCAPI 04) (ID 3562)

Presentation Number
LBA15_PR
Lecture Time
08:30 - 08:45
Speakers
  • Karim Fizazi (Villejuif, France)
Location
Pamplona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00

Abstract

Background

CUP are heterogeneous tumors that share the unique characteristic of metastases with no identifiable origin. The outcome of patients (pts) with CUP is poor despite empiric chemotherapy that has activity against a wide variety of neoplasms such as the cisplatin-gemcitabine combination (Culine S, JCO 2002). Molecular tests may identify primary sites in up to 80% of pts, and results suggest that at least 1/3 of identified primaries may not be sensitive to empiric chemotherapy used in CUPs (Gross-Goupil G 2012). In the GEFCAPI 04 phase III trial, we hypothesized that tailored treatment will improve outcomes.

Methods

Eligible pts had pathologically-confirmed metastatic CUPs and were treatment naïve. Pts belonging to pre-defined favorable subsets were excluded. After relevant workup had identified no primary site, pts were randomized 1:1 to either Arm A (Cisplatin 100 mg/m² d1+ Gemcitabine 1250 mg/m², day 1 and 8, q3w) or Arm B (gene expression test followed by à la carte treatment according to the suspected primary). The test consisted of the Tissue Of Origin (Pathwork, n = 21) or CancerTYPE ID (Biotheranostics, n = 222). The primary endpoint was PFS (HR = 0.625, power=80%, 5% bilateral test). Stratification was on site, PS and LDH level. Secondary endpoints were PFS in pts with pre-defined cancers likely insensitive to cisplatin-gemcitabine and OS.

Results

From 03/12 to 02/18, 243 pts from 4 EU countries were randomized (Arm A: 120, Arm B: 123). Primary cancers most often reported by tests were pancreatico-biliary cancer (19%), squamous cell carcinoma (11%, kidney cancer (8%), and lung cancer (8%). Treatment was tailored by molecular test results in 91/123 arm B pts (74%). PFS by central review was similar: HR = 0.95 (0.72-1.25); p = 0.7; medians: 5.3 m arm A vs 4.6 m arm B. PFS by local review also showed no significant difference: HR = 0.80 (0.60-1.06); p = 0.12; medians 5.8 vs 6.4 m. OS was also similar in the overall population (HR: 0.92 (0.69-1.23), medians: 10 vs 10.7 m) and in 60 pts with suspected cancers likely insensitive to GC.

Conclusions

In GEFCAPI 04, using a molecular test followed by tailored systemic treatment did not improve outcomes of pts with CUP.

Clinical trial identification

2011-A01202-39.

Legal entity responsible for the study

Institut Gustave Roussy.

Funding

Programme Hospitalier de Recherche Clinique (PHRC) from the French Ministry of Health.

Disclosure

K. Fizazi: Advisory / Consultancy: Astellas; Advisory / Consultancy: AAA; Advisory / Consultancy: Bayer; Advisory / Consultancy: Clovis; Advisory / Consultancy: Curevac; Advisory / Consultancy: Incyte; Advisory / Consultancy: Janssen; Advisory / Consultancy: MSD; Advisory / Consultancy: Orion; Advisory / Consultancy: Sanofi. R. Morales Barrera: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Astrazeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Asofarma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson and Jonhson; Honoraria (self), Advisory / Consultancy: Roche. C.A. Schnabel: Full / Part-time employment: bioTheranostics. All other authors have declared no conflicts of interest.

Collapse
Presidential Symposium III Proffered Paper session

LBA13 - CARD: Randomized, open-label study of cabazitaxel (CBZ) vs abiraterone (ABI) or enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC) (ID 3965)

Presentation Number
LBA13
Lecture Time
17:31 - 17:43
Speakers
  • Ronald De Wit (Rotterdam, Netherlands)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
16:30 - 18:15

Abstract

Background

Taxanes (docetaxel [DOC], CBZ) and androgen receptor-targeted therapies (ARTs; ABI, ENZ) are standard of care in mCRPC. The optimal treatment sequence is unknown. CARD (NCT02485691) compared CBZ vs ABI or ENZ in patients with mCRPC previously treated with DOC and the alternative ART.

Methods

Patients with mCRPC previously treated with ≥ 3 cycles of DOC and progressing ≤ 12 months (mo) on an alternative ART, in any order, were randomized 1:1 to CBZ (25 mg/m2 IV Q3W + prednisone + G-CSF) vs ABI (1000 mg PO + prednisone) or ENZ (160 mg PO). Randomization was stratified by ECOG PS (0/1 vs 2), time to progression on prior ART (≤ 6 vs 6–12 mo) and ART timing (before vs after DOC). Primary endpoint was radiographic PFS (rPFS), with 196 rPFS events needed to test HR 0.67 for CBZ (80% power, 2-sided alpha 0.05). Secondary efficacy endpoints and safety were assessed.

Results

Overall, 255 patients (median age 70, 31.0% ≥ 75 yrs) were randomized. Median number of cycles was higher for CBZ vs ART (7 vs 4). rPFS was significantly improved with CBZ vs ART (median 8.0 vs 3.7 mo; HR 0.54; 95% CI 0.40–0.73; p < 0.0001). CBZ also robustly improved OS (median 13.6 vs 11.0 mo; HR 0.64; 95% CI 0.46–0.89; p = 0.0078) despite crossover, as well as PFS (median 4.4 vs 2.7 mo; p < 0.0001), confirmed PSA50 response (35.7% vs 13.5%; p = 0.0002) and tumor response (36.5% vs 11.5%; p = 0.004). Pain response and time to symptomatic skeletal events were also significantly improved with CBZ. Grade ≥ 3 adverse events (AEs) occurred in 56.3% vs 52.4% of patients with CBZ vs ART. For CBZ vs ART, main grade ≥ 3 AEs were: renal disorders (3.2% vs 8.1%); infections (7.9% vs 7.3%); musculoskeletal pain/discomfort (1.6% vs 5.6%); cardiac disorders (0.8% vs 4.8%); spinal cord/nerve root disorders (2.4% vs 4.0%); asthenia/fatigue (4.0% vs 2.4%); diarrhea, peripheral neuropathy and febrile neutropenia (3.2% vs 0% for each). AEs led to death in 7 vs 14 patients (5.6% vs 11.3%) for CBZ vs ART.

Conclusions

CBZ significantly improved clinically important patient outcomes including rPFS and OS vs ART in patients with mCRPC previously treated with DOC and an alternative ART. CBZ should be the preferred option in this setting. Sanofi funded.

Clinical trial identification

NCT02485691.

Editorial acknowledgement

Editorial support was provided by Amber Wood, Danielle Lindley and Tina Wasmeier of MediTech Media and funded by Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

R. de Wit: Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory Boards and speaker fees: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory Boards and speaker fees: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Advisory Boards and institutional grants: Sanofi; Advisory / Consultancy, Research grant / Funding (self), Advisory Boards and institutional grants: Merck; Advisory / Consultancy, Research grant / Funding (institution), Advisory Boards and institutional grants: Bayer; Advisory / Consultancy, Research grant / Funding (self), Advisory Boards and institutional grants: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche. G. Kramer: Honoraria (self), Personal fess: Sanofi, Astellas, Takeda, Bayer, Janssen, Novartis, Ipsen, AstraZeneca; Research grant / Funding (self), Grant: Sanofi, Bayer. J. Eymard: Advisory / Consultancy, Board participation for Sanofi Aventis: Sanofi Aventis. J.S. de Bono: Honoraria (self), Advisory / Consultancy: AstraZeneca ; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech/Roche ; Honoraria (self), Advisory / Consultancy: Janssen Oncology; Honoraria (self), Advisory / Consultancy: Menarini Silicon Biosystems; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Sierra Oncology; Honoraria (self): Bioexcell; Advisory / Consultancy: Bayer; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: Genmab; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy: Orion Pharma GmbH; Advisory / Consultancy: Eisai, BioXCel therapeutics. C.N. Sternberg: Honoraria (self): Janssen; Honoraria (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self): Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Honoraria (institution), Research grant / Funding (institution): Roche-Genentech, Bayer, Sanofi Genzyme, Janssen, Medivation, Exelixis. K. Fizazi: Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (institution), Advisory / Consultancy: Astrazeneca; Honoraria (institution), Advisory / Consultancy: AAA; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Curevac; Honoraria (institution), Advisory / Consultancy: Essa; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: Orion; Honoraria (institution), Advisory / Consultancy: Sanofi. B. Tombal: Research grant / Funding (self): Astellas; Research grant / Funding (self): Janssen; Research grant / Funding (self), Non-remunerated activity/ies: Sanofi-Genzyme; Research grant / Funding (self): Amgen; Research grant / Funding (self): Ferring. A. Bamias: Honoraria (self): Astellas; Honoraria (self): Sanofi; Research grant / Funding (self): Janssen. J. Carles: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson and Johnson; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas Pharma; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: Asofarma. R. Iacovelli: Honoraria (self): Sanofi; Honoraria (self): Janssen; Honoraria (self): Pfizer; Honoraria (self): IPSEN; Honoraria (self): Novartis; Honoraria (self): BMS; Honoraria (self): MSD. B. Melichar: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer. A. Ozatilgan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Sanofi. C. Geffriaud-Ricouard: Full / Part-time employment: Sanofi. D. Castellano: Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: Roche; Honoraria (self), Personal fees: Sanofi; Honoraria (self), Personal fees: Janssen; Honoraria (self), Personal fees: Astellas; Honoraria (self), Personal fees: Bayer; Honoraria (self), Personal fees: BMS; Honoraria (self), Personal fees: MSD; Honoraria (self), Personal fees: Merck Serono; Honoraria (self), Personal fees: Pierre Fabre; Honoraria (self), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Lilly. All other authors have declared no conflicts of interest.

Collapse
Poster Discussion 1 – Translational research Poster Discussion session

LBA17 - Harmonization study of tumour mutational burden determination in non-small cell lung cancer (NSCLC) (ID 5443)

Presentation Number
LBA17
Lecture Time
09:15 - 09:15
Speakers
  • Eva M Garrido-Martin (Madrid, Spain)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
08:45 - 09:45

Abstract

Background

Tumour mutational burden (TMB) is an emerging predictive biomarker for patients with NSCLC treated with checkpoint inhibitors. A number of gene panels are available for TMB calculation, each with different characteristics, including the number of genes and the selected individual genes, and distinct informatics algorithms that may lead to different results. We have performed a correlation study of 3 panels in a large cohort of clinically annotated NSCLC patients.

Methods

We have blindly evaluated the concordance of tissue TMB assessments of two different commercially available panels: TSO500 (performed at HU 12 de Octubre) and Oncomine TML (performed at CIOCC), with Foundation One® CDx (F1CDx-Penzberg, Germany). A cohort of 100 early stage NSCLC tumour samples is being utilized. PD-L1 expression was analyzed in all samples with 22C3 PharmDX.

Results

The determination of TMB for all panels was calculated as total number of mutations (synonym plus non-synonym) per megabase of exonic DNA. Four samples did not have enough sequencing depth for TML panel (n = 96 was used for all correlations). TMB values correlated with F1CDx with a R2 =0.8775 for TSO500; and with a R2 = 0.8119 for TML. The correlation between TSO500 and TML was R2 = 0.8545. Results obtained for each panel are indicated in the table below. Additionally, TMB values were evaluated in the samples grouped by < 1%, >1% and >50% of PD-L1 expression. In tumours PD-L1<1% (n = 55), TMB values correlated with F1CDx with a R2 = 0.9120 (TSO500) and a R2 = 0.8768 (TML), respectively. In tumours PD-L1>1% (n = 41), TMB values correlated with F1CDx with a R2 = 0.7466 (TSO500) and a R2 = 0.5735 (TML), respectively.

LBA17

NSCLC Cohort (n = 96)TSO500TMLF1CDx
Total TMB Range (muts/Mb) Average (muts/Mb) Median (muts/Mb) % of samples with TMB >10 muts/Mb % of samples with TMB >13 muts/Mb % of samples with TMB >16 muts/Mb1-84 13 9 46% 31% 20%0-60 13 10 50% 38% 24%0-74 14 10 51% 35% 28%
PDL1 <1% (n = 55)TSO500TMLF1CDx
TMB high (≥10) TMB med/low (<10)53% 47%64% 36%51% 49%
PDL1 >1% (n = 55)TSO500TMLF1CDx
TMB high (≥10) TMB med/low (<10)59% 41%63% 37%51% 49%
PDL1 >50% (n = 10)TSO500TMLF1CDx
TMB high (≥10) TMB med/low (<10)70% 30%80% 20%40% 60%

Conclusions

There is a strong correlation between TMB determined by TSO500 and TML panels with F1CDx, particularly for tumours with low PD-L1 expression. The range of TMB values is lower with TSO500 and TML, for samples determined TMBhigh by F1CDx. Cut-off values may be lowered for these panels in order to meet F1CDx TMB categories.

Legal entity responsible for the study

Fundacion para la Investigacion Biomedica del Hospital Doce de Octubre, Madrid, Spain.

Funding

Bristol-Myers Squibb.

Disclosure

E.M. Garrido-Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Illumina. S. Hernandez Prieto: Honoraria (institution): Roche; Honoraria (institution): Thermo Fisher; Honoraria (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): AbbVie. S. Ponce Aix: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: AstraZeneca. P. Garrido: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boerhinger Ingelheim; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Guardant Health; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (institution), Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Sysmex; Honoraria (institution), Advisory / Consultancy: Blueprint Medicines; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Gilead; Speaker Bureau / Expert testimony: Rovi; Honoraria (institution): Pharmamar; Honoraria (institution): Celgene; Honoraria (institution): Sanofi; Honoraria (institution): GSK, Theradex Oncology. F. Lopez-Rios: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Thermo Fisher; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: AbbVie; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Bayer. L. Paz-Ares: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pharmamar; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sysmex; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Adacap; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Blueprint. All other authors have declared no conflicts of interest.

Collapse
Proffered Paper - Breast cancer, early stage Proffered Paper session

Invited Discussant LBA18 and LBA19 (ID 6651)

Lecture Time
15:15 - 15:30
Speakers
  • Antonio Llombart Cussac (Lleida, Spain)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
14:45 - 16:15
Presidential Symposium III Proffered Paper session

Invited Discussant LBA13 (ID 7304)

Lecture Time
17:43 - 17:53
Speakers
  • Silke Gillessen (Manchester, United Kingdom)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
16:30 - 18:15
Poster Discussion 1 – Translational research Poster Discussion session

Invited Discussant 91PD, LBA16, 1875PD and 1876PD (ID 6947)

Lecture Time
08:45 - 09:05
Speakers
  • Jos Jonkers (Amsterdam, Netherlands)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
08:45 - 09:45
Presidential Symposium III Proffered Paper session

LBA14_PR - IMvigor130: Efficacy and safety from a phase III study of atezolizumab (atezo) as monotherapy or combined with platinum-based chemotherapy (PBC) vs placebo + PBC in previously untreated locally advanced or metastatic urothelial carcinoma (mUC) (ID 2800)

Presentation Number
LBA14_PR
Lecture Time
17:53 - 18:05
Speakers
  • Enrique Grande (Madrid, Spain)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
16:30 - 18:15

Abstract

Background

First-line (1L) mUC treatment (tx) includes cisplatin (cis)- or carboplatin (carbo)-based chemotherapy or checkpoint inhibitors, depending on patient (pt) eligibility and PD-L1 status. IMvigor130 is a phase 3, global, multicentre, randomised, partially blinded study evaluating atezo (anti–PD-L1) alone or with PBC vs placebo + PBC in untreated mUC.

Methods

IMvigor130 enrolled 1213 PBC-eligible pts with mUC. Pts were randomised 1:1:1 to Arm A (atezo + PBC [gemcitabine (gem) + either cis or carbo]), Arm B (atezo) or Arm C (placebo + PBC). Gem 1000 mg/m2 IV was given on Day (D) 1 and D8, carbo AUC 4.5 IV or cis 70 mg/m2 IV on D1 and atezo/placebo or atezo 1200 mg IV on D1 of each 3-wk tx cycle. Tumours were assessed at baseline and every 9 wk until (INV)-assessed PD per RECIST 1.1 or other events. Coprimary efficacy endpoints are INV-assessed PFS and OS (Arm A vs C) and OS (Arm B vs C, hierarchical approach) per RECIST 1.1. Final PFS (Arm A vs C) and interim OS are shown here.

Results

With a median follow-up of 11.8 mo, median PFS was 8.2 mo in Arm A vs 6.3 mo in Arm C (HR, 0.82 [95% CI: 0.70, 0.96]; P = 0.007). The comparison of OS did not cross the prespecified interim efficacy boundary, with a median of 16.0 mo in Arm A and 13.4 mo in Arm C (HR, 0.83 [95% CI: 0.69, 1.00]; P = 0.027; Table). For Arm B vs C, the median OS was 15.7 and 13.1 mo, respectively (HR, 1.02 [95% CI: 0.83, 1.24]), for ITT pts and not estimable and 17.8 mo, respectively (HR, 0.68 [95% CI: 0.43, 1.08]), for PD-L1 IC2/3 pts. ORRs were 47%, 23% and 44% and CR rates were 13%, 6% and 7% for Arms A, B and C, respectively. AEs that led to tx withdrawal occurred in 34%, 6% and 34% of pts in Arms A, B and C, respectively.

LBA14_PR

Formally Testeda CoPrimary Endpoints
Arm AArm C
Atezo + PBCPlacebo + PBC
n = 447n = 397
Median PFS8.26.3
 (95% CI), mo(6.5, 8.3)(6.2, 7.0)
HR (95% CI)0.82 (0.70, 0.96)
P value [one-sided]P = 0.007
Median OS16.013.4
 (95% CI), mo(13.9, 18.9)(12.0, 15.2)
HR (95% CI)0.83 (0.69, 1.00)
P value [one-sided]P = 0.027

Stratification factors were PD-L1 status on tumour-infiltrating immune cells (IC; IC0 vs IC1 vs IC2/3), Bajorin risk factors/liver metastases (0 vs 1 vs 2 or pts with liver metastases) and investigator (INV)-specified PBC (gem + carbo vs gem + cis). Data cutoff: 31 May 2019.

PFS and OS for Arm A vs C were formally tested with type I error control for multiple comparisons with a prespecified interim efficacy boundary P value of 0.007; Arm B vs C in ITT and PD-L1 IC2/3 pts were not formally tested.

Conclusions

Adding atezo to PBC for 1L mUC tx prolonged PFS vs PBC alone in pts with untreated mUC. The combination safety profile was consistent with that observed for the individual agents.

Clinical trial identification

NCT02807636.

Editorial acknowledgement

Medical writing assistance was provided by Paige Davies, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

E. Grande: Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ipsen; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony: Sanofi-Genzyme; Speaker Bureau / Expert testimony: Adacap; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: EUSA Pharma; Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony, Research grant / Funding (self): Lexicon; Speaker Bureau / Expert testimony: Celgene; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): MTEM/Threshold; Advisory / Consultancy: Enets; Officer / Board of Directors: Getne; Officer / Board of Directors: Gethi. M. Galsky: Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: BioMotiv; Advisory / Consultancy: Glaxo Smith Kline; Advisory / Consultancy: Lilly; Advisory / Consultancy: Astellas; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: EMD-Serono; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Incyte; Advisory / Consultancy: Aileron; Advisory / Consultancy: Dracen; Advisory / Consultancy: Inovio; Advisory / Consultancy: Dragonfly. J.A. Arranz Arija: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pierre Fabre Oncology; Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Roche; Honoraria (self): Cilag; Travel / Accommodation / Expenses: Essa; Travel / Accommodation / Expenses: Ferring. M. De Santis: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen, Astellas, AstraZeneca, Bayer, Bioclin; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS, EISAI, Roche; Honoraria (self), Travel / Accommodation / Expenses: Clovis, Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: ESSA; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ferring; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: OncoGenex; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre Oncology; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sandoz; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SeaGen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Shionogi, Synthon, Takeda; Non-remunerated activity/ies: EAU Prostrate Cancer Guidelines; Non-remunerated activity/ies: ESMO Bladder Cancer Practice Guidelines; Non-remunerated activity/ies: S3 Blasenkarzinom Leitlinien. I.D. Davis: Honoraria (institution), Advisory / Consultancy: Amrad; Honoraria (institution), Advisory / Consultancy: Sanofi (and Sanofi-aventis); Honoraria (institution), Advisory / Consultancy: NovoNordisk; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Pharmion ; Honoraria (institution), Advisory / Consultancy: Wyeth; Honoraria (institution), Advisory / Consultancy: Schering-Plough; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: GSK; Honoraria (institution), Advisory / Consultancy: Medivation; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Dendreon; Honoraria (institution), Advisory / Consultancy: Ipsen; Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Eisai; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: BMS, AstraZeneca; Research grant / Funding (institution): NHMRC Practitioner Fellowship; Officer / Board of Directors: Anzup. U.F.F. De Giorgi: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. M. Mencinger: Advisory / Consultancy: Sanofi; Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: roche; Honoraria (self), Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Speaker Bureau / Expert testimony: Astellas. E. Kikuchi: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Nippon; Research grant / Funding (institution): Kayaku; Honoraria (self), Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): ONO; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Kissei; Honoraria (self): ASKA; Honoraria (self): Shinyaku; Honoraria (self): Pfizer. X. Garcia del Muro: Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Lilly; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Eusapharma; Honoraria (self), As a speaker or moderator in Scientific Meeting: Astellas. M. Gumus: Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen. M. Özgüroğlu: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Roche; Travel / Accommodation / Expenses: BMS. A. Rezazadeh Kalebasty: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech, Inc./Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Exelixis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Macrogenics; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): beyond spring; Research grant / Funding (institution): Bioclin; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Bavarian Nordic; Research grant / Funding (institution): Seattle Genetics; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Amgen; Shareholder / Stockholder / Stock options: ECOM; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Travel / Accommodation / Expenses: Prometheus Labs. B.Y. Alekseev: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ferring. F.A.B. Schutz: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Spouse / Financial dependant: Ipsen. A. Mecke: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche. S. Mariathasan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/GNE. A. Thastrom: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech, Inc.. A. Bamias: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.

Collapse
Presidential Symposium I Proffered Paper session

LBA1 - Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study) (ID 4627)

Presentation Number
LBA1
Lecture Time
16:30 - 16:42
Speakers
  • Antonio González Martín (Madrid, Spain)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
16:30 - 18:20

Abstract

Background

Niraparib has shown progression-free survival (PFS) benefit in recurrent OC after platinum-based chemotherapy (CT) in all patients (pts) regardless of BRCA status. This study evaluated the efficacy of niraparib in pts with newly diagnosed advanced OC after completion of first-line (1L) CT regardless of BRCA status.

Methods

This double-blind, placebo (PBO)-controlled phase III trial evaluated niraparib in pts with newly diagnosed advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response (CR or PR) to 1L platinum-based CT. Stratification factors were best response to the 1L CT regimen (CR/PR), receipt of neoadjuvant CT (NACT; yes/no), and homologous recombination deficiency (HRD) status (positive/negative/unknown) per the Myriad myChoice HRD test. Pts received niraparib or PBO once daily. PFS assessed by blinded independent central review was the primary end point, analyzed using a stratified Cox proportional hazards model and hierarchically tested in HRD-positive (HRDpos) pts and then the overall population.

Results

Of 733 randomized pts (niraparib, 487; PBO, 246), 373 (51%) were HRDpos (niraparib, 247; PBO, 126). Overall, 35% had stage IV disease, 67% received NACT, and 31% had a PR to 1L CT. Niraparib-treated pts in the HRDpos subgroup and overall population had a significant reduction in the risk of disease recurrence or death with a substantial improvement in PFS (Table). All subgroups showed a sustained and durable treatment effect. The most common grade ≥3 adverse events were anemia (31%), thrombocytopenia (29%), and neutropenia (13%). No treatment-related deaths occurred.

LBA1

Niraparib mPFS (95% CI)PBO mPFS (95% CI)Hazard Ratio (95% CI) P Value
HRDpos subgroup21.9 (19.3–NE)10.4 (8.1–12.1)0.43 (0.31–0.59) P < 0.0001
Overall population13.8 (11.5–14.9)8.2 (7.3–8.5)0.62 (0.5–0.75) P < 0.0001

CI, confidence interval; mPFS, median progression-free survival; NE, not estimable.

Conclusions

Niraparib significantly improved PFS in pts with newly diagnosed advanced OC, including pts at high risk of progressive disease in the HRDpos subgroup and overall population. No new safety signals were identified. Niraparib should be considered as a treatment option for pts with advanced OC after completion of 1L CT.

Clinical trial identification

NCT02655016.

Editorial acknowledgement

Writing and editorial support, funded by Tesaro, a GSK Company (Waltham, MA, USA) and coordinated by Ashujit Tadge, PhD of TESARO, was provided by Nicole Renner, PhD of Ashfield Healthcare Communications (Middletown, CT, USA) and Adrienne M. Schreiber, of Tesaro (Waltham, MA, USA).

Legal entity responsible for the study

Tesaro: A GSK Company.

Funding

Tesaro: A GSK Company.

Disclosure

A. González Martín: Research grant / Funding (institution): Roche; Advisory / Consultancy: AstraZeneca Tesaro; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Tesaro, Inc.. B. Pothuri: Advisory / Consultancy: Tesaro, Inc.; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Intuitive. I.B. Vergote: Advisory / Consultancy: GCI Health, Oncoinvent AS, Roche NV; Research grant / Funding (institution): Roche; Advisory / Consultancy: Genmab A/S, Advaxid Inc, Morphotek Inc; Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Cerulean Pharma Inc, Novocure GMBH; Advisory / Consultancy: AstraZeneca, Mateon Therapeutics Inc; Advisory / Consultancy: Immunogen, Eli Lilly; Advisory / Consultancy, Research grant / Funding (self): Amgen; Advisory / Consultancy: Theradex Europe Limited, Pfizer, Debiopharma International SA; Advisory / Consultancy: Vifor Pharma Belgie NV, Novartis, MSD Belgium BVBA; Advisory / Consultancy: Oxigene, Janssen-Dilag, Nektar Therapeutics, Bayer; Travel / Accommodation / Expenses: Tesaro, Theradex, Elsevier. R.D. Christensen: Advisory / Consultancy: Tesaro: A GSK Company. W. Graybill: Advisory / Consultancy, Speaker Bureau / Expert testimony: Tesaro, Inc.. M.R. Mirza: Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro, Inc.. D. Lorusso: Honoraria (self), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Clovis Oncology; Honoraria (self), Personal fees: Genmab; Honoraria (self), Personal fees: Immunogen; Honoraria (self), Personal fees: Pharma Mar S.A; Honoraria (self), Personal fees: Amgen; Honoraria (self), Personal fees: Merck; Research grant / Funding (institution): Pharma Mar S.A; Research grant / Funding (institution): Merck. G. Freyer: Honoraria (self), Personal fees: Tesaro: A GSK Company; Honoraria (self), Personal fees: Clovis Oncology; Honoraria (self), Personal fees: Bristol-Myers Squibb ; Honoraria (self), Personal fees: MSD; Honoraria (self), Personal fees: Pfizer Inc. ; Honoraria (self), Personal fees: Novartis; Honoraria (self), Personal fees: Eli Lilly ; Honoraria (self), Personal fees: Biogara S.A.S; Honoraria (self), Research grant / Funding (institution), Personal fees: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Personal fees: Roche Holding AG ; Honoraria (self), Research grant / Funding (institution), Personal fees: Mylan. F. Backes: Honoraria (self), Advisory / Consultancy, Personal fees: Clovis Oncology ; Honoraria (self), Advisory / Consultancy, Personal fees: Merck ; Honoraria (self), Advisory / Consultancy, Personal fees: Eisai ; Honoraria (self), Personal fees: Tesaro; Honoraria (self), Personal fees: Agenus; Honoraria (self), Personal fees: CEC Oncology; Research grant / Funding (institution): Immunogen. A. Redondo: Advisory / Consultancy, Research grant / Funding (institution): Pharmamar; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Research grant / Funding (institution): Eisai. R.G. Moore: Research grant / Funding (institution): Angle PLC; Advisory / Consultancy: Fugirebio Diagnostics Inc. R.E. O’Cearbhaill: Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: GlaxoSmithKline. Y. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro, Inc.. D. Gupta: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro, Inc.. B.J. Monk: Honoraria (self), Advisory / Consultancy: AbbVie, Advaxis; Honoraria (self), Advisory / Consultancy: Agenus, Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca, Biodesix; Honoraria (self), Advisory / Consultancy: Clovis, Conjupro; Honoraria (self), Advisory / Consultancy: Genmab, Gradalis; Honoraria (self), Advisory / Consultancy: ImmunoGen, Immunomedics; Honoraria (self), Advisory / Consultancy: Incyte, Janssen; Honoraria (self), Advisory / Consultancy: Mateon, Merck; Honoraria (self), Advisory / Consultancy: Myriad, Perthera; Honoraria (self), Advisory / Consultancy: Pfizer, Precision; Honoraria (self), Advisory / Consultancy: Puma, Roche; Honoraria (self), Advisory / Consultancy: Samumed, Takeda; Honoraria (self), Advisory / Consultancy: Tesaro, VB. All other authors have declared no conflicts of interest.

Collapse
Proffered Paper - Breast cancer, early stage Proffered Paper session

LBA18 - Clinical outcomes by chemotherapy regimen in patients with RS 26-100 in TAILORx (ID 6136)

Presentation Number
LBA18
Lecture Time
14:45 - 15:00
Speakers
  • Joseph Sparano (Bronx, NY, United States of America)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
14:45 - 16:15

Abstract

Background

The recurrence score (RS) based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low. There is little information from prospective clinical trials, however, regarding outcomes for patients with a high RS treated with chemotherapy regimens including taxanes and/or anthracyclines.

Methods

Women with hormone-receptor-positive, HER2-negative, axillary-node-negative breast cancer and a high RS of 26-100 were assigned to receive endocrine therapy plus a chemotherapy regimen selected by the treating physician.

Results

Among the 9719 eligible women, 1389 (14%) had a RS of 26-100.The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-FU in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). The estimated rates of freedom from recurrence of breast cancer at a distant site were 93.0% (standard error [SE]+0.8%) at 5 years and 86.8% (SE + 1.7%) at 9 years. In contrast, the projected rates of freedom from distant recurrence in this population if treated with endocrine therapy alone was estimated to be 78.8% (SE ± 14.0%) at 5 years and 65.4% (SE ± 10.4%) at 9 years when estimating outcomes based on the treatment effect of chemotherapy noted in the HER2-negative cohort of the B20 trial. Five-year rates of freedom from distant recurrence ranged from 92.3% to 95.5% for all chemotherapy regimens with the exception of CMF (88.5%).

Conclusions

The estimated rate of freedom from distant recurrence in women with a RS of 26-100 treated with a variety of adjuvant taxane and/or anthracycline-containing chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population.

Clinical trial identification

NCT00310180.

Legal entity responsible for the study

ECOG-ACRIN Cancer Research Group.

Funding

USA National Cancer Institute, Genomic Health.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Presidential Symposium III Proffered Paper session

LBA10_PR - ClarIDHy: A global, phase III, randomized, double-blind study of ivosidenib (IVO) vs placebo in patients with advanced cholangiocarcinoma (CC) with an isocitrate dehydrogenase 1 (IDH1) mutation (ID 1867)

Presentation Number
LBA10_PR
Lecture Time
16:30 - 16:42
Speakers
  • Ghassan K. Abou-Alfa (New York, NY, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
16:30 - 18:15

Abstract

Background

CC is a rare cancer for which there are limited effective therapies. IDH1 mutations occur in up to ∼15% of CC, resulting in production of the oncometabolite, D-2-hydroxyglutarate (2-HG), which promotes oncogenesis. IVO (AG-120) is a first-in-class, oral, small-molecule inhibitor of the mutant IDH1 (mIDH1) protein.

Methods

Patients (pts) with mIDH1 CC were randomized 2:1 to IVO (500 mg once daily) or matched PBO and stratified by number of prior systemic therapies (1 or 2). Key eligibility: unresectable or metastatic mIDH1 CC based on central testing; ECOG PS 0–1; measurable disease (RECIST v1.1). Crossover from PBO to IVO was permitted at radiographic PD. Primary endpoint: progression-free survival (PFS) by central review. Secondary endpoints included safety, ORR, PFS (local investigator review), and overall survival (OS; by ITT). Crossover-adjusted OS was derived using rank preserved structural failure time (RPSFT).

Results

As of 31Jan2019, 185 pts were randomized to IVO (n = 124) or PBO (n = 61). Median age 62 y, M/F 68/117, 91% intrahepatic CC, 92% metastatic disease, 43% had 2 prior therapies. Primary endpoint (PFS by central review) was met: HR = 0.37 (95% CI 0.25, 0.54; p < 0.001); median PFS was 2.7 (IVO) vs. 1.4 (PBO) mo. PFS rates at 6 and 12 mo were 32.0% and 21.9% in IVO arm; no PBO pts were progression-free for ≥6 mo at data cutoff. ORR for IVO was 2.4% (3 PRs), with 50.8% SD (n = 63) vs. 0% ORR in PBO and 27.9% SD (n = 17). By ITT analysis, median OS was 10.8 mo for IVO and 9.7 mo for PBO (HR = 0.69; one-sided p = 0.06) with 57% of PBO pts crossed over to IVO. The RPSFT-adjusted median OS was 6 mo for PBO (HR = 0.46; p = 0.0008). PFS by local review HR = 0.47 (p < 0.001). Common TEAEs (>15%) in IVO arm: nausea (32.1%), diarrhea (28.8%), fatigue (23.7%), cough (19.2%), abdominal pain (18.6%), ascites (18.6%), decreased appetite (17.3%), anemia (16.0%), vomiting (16.0%). Grade ≥3 adverse events reported in 46% IVO vs. 36% PBO. There were no treatment-related deaths.

Conclusions

IVO resulted in significant improvement in PFS and favorable OS trend vs. PBO. This is the first pivotal study demonstrating the clinical benefit of targeting mIDH1 in pts with advanced mIDH1 CC.

Clinical trial identification

NCT02989857.

Editorial acknowledgement

Yvonna Fisher-Jeffes of Agios Pharmaceuticals, Inc and Helen Varley of Envision Pharma Group.

Legal entity responsible for the study

Agios Pharmaceuticals, Inc.

Funding

Agios Pharmaceuticals, Inc.

Disclosure

G.K. Abou-Alfa: Advisory / Consultancy, Research grant / Funding (institution): 3DMedcare; Advisory / Consultancy: ActaBiologica; Advisory / Consultancy, Research grant / Funding (institution): Agios; Advisory / Consultancy: Alignmed; Advisory / Consultancy: Amgen; Advisory / Consultancy: Antengene; Advisory / Consultancy: Aptus; Research grant / Funding (institution): Array; Advisory / Consultancy: Aslan; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Beigene; Advisory / Consultancy: Bioline; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Boston Scientifc; Advisory / Consultancy: Bridgebio; Advisory / Consultancy: Carsgen; Advisory / Consultancy, Research grant / Funding (institution): Casi; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Cipla; Advisory / Consultancy: CytomX; Advisory / Consultancy: Daiichi; Advisory / Consultancy: Debio; Advisory / Consultancy: Delcath; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Genentech; Advisory / Consultancy: Genoscience; Advisory / Consultancy, Research grant / Funding (institution): Halozyme; Advisory / Consultancy: Hengrui; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy: Inovio; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Jazz; Advisory / Consultancy: Janssen; Advisory / Consultancy: Kyowa Kirin; Advisory / Consultancy: LAM; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Loxo; Research grant / Funding (institution): Mabvax; Advisory / Consultancy: Merck; Advisory / Consultancy: Mina; Research grant / Funding (institution): Novartis; Advisory / Consultancy: Novella; Research grant / Funding (institution): OncoQuest; Advisory / Consultancy: Onxeo; Advisory / Consultancy: PCI Biotech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Pieris; Research grant / Funding (institution): Polaris; Research grant / Funding (institution): Puma; Advisory / Consultancy, Research grant / Funding (institution): QED; Advisory / Consultancy: Redhill; Research grant / Funding (institution): Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Silenseed; Advisory / Consultancy: Sillajen; Advisory / Consultancy: Sobi; Advisory / Consultancy: Targovax; Advisory / Consultancy: Tekmira; Advisory / Consultancy: Twoxar; Advisory / Consultancy: Vicus; Advisory / Consultancy: Yakult; Advisory / Consultancy: Yiviva. T. Macarulla Mercade: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): Sanofi; Honoraria (self): Tesaro; Honoraria (self), Advisory / Consultancy: Shire; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Celgene; Advisory / Consultancy: QDE; Advisory / Consultancy, Travel / Accommodation / Expenses: H3B; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi/Aventis; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Baxalta; Honoraria (self): Genzyme; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Aslan; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (institution): Genentech; Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Hallozyme; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Merrimarck; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Novocure; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pharmacyclics. M. Javle: Research grant / Funding (self): QED; Research grant / Funding (self): Novartis; Honoraria (self): Taiho; Research grant / Funding (self): Meclun; Honoraria (self): Seattle Genetics; Research grant / Funding (institution): Arqule; Honoraria (self): Merck; Research grant / Funding (institution): Lilly; Advisory / Consultancy: Origimed; Advisory / Consultancy: More Health; Advisory / Consultancy: EDO. R.K. Kelley: Advisory / Consultancy, Research grant / Funding (institution): Agios; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): QED; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): EMD Serono; Advisory / Consultancy: Target Pharma Solutions; Advisory / Consultancy: Genentech/Roche. J.M. Cleary: Honoraria (self), Travel / Accommodation / Expenses: Agios; Honoraria (self), Travel / Accommodation / Expenses: BMS; Research grant / Funding (self): Merck; Research grant / Funding (self): Tesaro; Travel / Accommodation / Expenses: Roche. D.V. Catenacci: Honoraria (self): Astellas; Honoraria (self): Five Prime; Honoraria (self): BMS; Honoraria (self): Merck; Honoraria (self): Lilly; Honoraria (self): Taiho; Honoraria (self): Daichii Sankyo; Honoraria (self): Genentech/Roche; Honoraria (self): Foundation Medicine; Honoraria (self): Tempus; Honoraria (self): Guardant Health. M.J. Borad: Research grant / Funding (institution): Senhwa Pharmaceuticals; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Agios Pharmaceuticals; Research grant / Funding (institution): Halozyme Pharmaceuticals; Research grant / Funding (institution): Celgene Pharmaceuticals; Research grant / Funding (institution): EMD Merck Serono; Research grant / Funding (institution): Toray; Research grant / Funding (institution): Dicerna; Research grant / Funding (institution): Taiho Pharmaceuticals; Research grant / Funding (institution): Sun Biopharma; Research grant / Funding (institution): Isis Pharmaceuticals; Research grant / Funding (institution): Redhill Pharmaceuticals; Research grant / Funding (institution): Boston Biomed; Research grant / Funding (institution): Basilea; Research grant / Funding (institution): Incyte Pharmaceuticals; Research grant / Funding (institution): Mirna Pharmaceuticals; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Bioline; Research grant / Funding (institution): Sillajen; Research grant / Funding (institution): ARIAD; Research grant / Funding (institution): PUMA; Research grant / Funding (institution): Novartis Pharmaceuticals; Research grant / Funding (institution): QED Pharmaceuticals; Research grant / Funding (institution): Pieris; Honoraria (self): Exelixis; Honoraria (self): G1 Therapeutics; Honoraria (self): Immunovative Therapies; Shareholder / Stockholder / Stock options: OncBioMune Pharmaceuticals; Honoraria (self): Western Oncolytics; Honoraria (self): Lynx Group; Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Inspyr Therapeutics; Honoraria (self): ADC Therapeuctics; Shareholder / Stockholder / Stock options: Intercept; Shareholder / Stockholder / Stock options: AVEO. J.A. Bridgewater: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Incyte; Advisory / Consultancy: Basilea; Speaker Bureau / Expert testimony: Celgene; Speaker Bureau / Expert testimony, Research grant / Funding (self): Amgen; Travel / Accommodation / Expenses: MDS Oncology; Travel / Accommodation / Expenses: Bristol-Myers Squibb/Medarex; Travel / Accommodation / Expenses: Bristol-Myers Squibb. W.P. Harris: Advisory / Consultancy: NeoTherma; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Bristo-Myers Squibb; Research grant / Funding (institution): ArQule; Research grant / Funding (institution): Halozyme; Research grant / Funding (institution): BTG; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Merck. A.G. Murphy: Research grant / Funding (self): Bristol-Myers Squibb. D. Oh: Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho; Advisory / Consultancy: ASLAN; Advisory / Consultancy: Halozyme; Research grant / Funding (institution): Array; Research grant / Funding (institution): Eli Lilly. B. Wu: Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Agios. L. Jiang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Agios. C. Gliser: Shareholder / Stockholder / Stock options, Full / Part-time employment: Agios. S.S. Pandya: Shareholder / Stockholder / Stock options, Full / Part-time employment: Agios. J.W. Valle: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: NuCana; Advisory / Consultancy, Speaker Bureau / Expert testimony: Abbott; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Sirtex; Advisory / Consultancy: Agios; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Baxalta; Advisory / Consultancy: Bioven; Advisory / Consultancy: Delcath; Advisory / Consultancy: Genoscience Pharma; Advisory / Consultancy: Incyte; Advisory / Consultancy: Keocyt; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Midatech; Advisory / Consultancy: Mundipharma; Advisory / Consultancy: PCI Biotech; Advisory / Consultancy: Pieris Pharmaceuticals; Advisory / Consultancy: QED Pharmaceuticals. A.X. Zhu: Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy, Research grant / Funding (self): Lilly; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Roche/Genentech. All other authors have declared no conflicts of interest.

Collapse