Found 20 Presentations For Request "LBA1"

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
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.

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Proffered Paper - Breast cancer, early stage Proffered Paper session

LBA19 - Peripheral neuropathy (PN), thrombocytopenia (TCP) and central nervous system (CNS) recurrence: An update of the phase III KATHERINE trial of post-neoadjuvant trastuzumab emtansine (T-DM1) or trastuzumab (H) in patients (pts) with residual invasive HER2-positive breast cancer (BC) (ID 4667)

Presentation Number
LBA19
Lecture Time
15:00 - 15:15
Speakers
  • Michael Untch (Berlin, Germany)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
14:45 - 16:15

Abstract

Background

We analyzed KATHERINE trial (NCT01772472) data to assess TCP, PN and CNS recurrence, key considerations in anti-HER2 treatment of BC pts.

Methods

Pts received 14 cycles of post-neoadjuvant T-DM1 (3.6 mg/kg IV q3w) or H (6 mg/kg IV q3w). Safety (per NCI CTCAE v4.0; all pts receiving ≥1 dose of study drug) and CNS recurrence (intent-to-treat population) were assessed.

Results

Baseline (BL) neuropathy was well balanced between arms (T-DM1 22.7%; H 21.4%). In both arms, BL neuropathy was not associated with higher PN incidence (T-DM1 36.3% H 17.5% vs T-DM1 31.1% H 16.8%) however it was associated with longer median PN duration and lower resolution rate (352–337 days [d] 66–64% vs 243–232 d 81–83%). PN incidence was similar, irrespective of prior taxane (docetaxel T-DM1 32%; H 18%; paclitaxel T-DM1 32%; H 17%). In the T-DM1 arm, prior platinum was associated with higher TCP incidence (mostly grade 1–2) (36% vs 27%) while median duration and resolution rate of grade 3–4 TCP were similar regardless of prior platinum (33 d vs 29 d; 95% vs 96%). In the H arm, TCP rate was only 2.4% precluding further analysis. The numerically higher rate of CNS recurrence as first IDFS event for T-DM1 may be explained by competing risk, as observed in H adjuvant trials. T-DM1 was not associated with an increased overall risk of CNS recurrence and there was no evidence of subsequent overall survival (OS) detriment (Table).

CNS recurrence analysis

CNS recurrenceT-DM1 (n = 743)H (n = 743)
Pts with CNS recurrence, n (%)45 (6.1)40 (5.4)
As first IDFS eventa44 (5.9)32 (4.3)
After first IDFS eventb1 (0.1)8 (1.1)
Pts with CNS as only eventc36 (4.8)21 (2.8)
Median time to CNS recurrence, m17.511.9
OS post CNS recurrenceT-DM1 (n = 45)H (n = 40)
Pts with OS event, n (%)26 (57.8)21 (52.5)
Pts without OS event, n (%)19 (42.2)19 (47.5)
Median time to event (95% CI), m12.5 (8.6–26.6)14.3 (7.6–29.8)
Unstratified HR (95% CI)1.07 (0.60–1.91)
3-year event-free rate, % (95% CI)24.2 (5.05–43.3)25.4 (6.81–44.0)
CNS recurrence withina or afterb 61 days of first IDFS event cAny time; m, months

Conclusions

BL neuropathy may impact duration and resolution of PN with T-DM1 or H, but PN incidence was not affected by BL neuropathy or type of prior taxane. Prior platinum was associated with higher TCP incidence in the T-DM1 arm. The numerical difference in CNS recurrence as first IDFS event for T-DM1 vs H may be explained by competing risk and had no detrimental effect on OS.

Clinical trial identification

NCT01772472.

Editorial acknowledgement

Medical writing support was provided by Ify Sargeant of Twist Medical LLC and funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

M. Untch: Honoraria (institution), Non-remunerated activity/ies: AbbVie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution), Non-remunerated activity/ies: BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH; Honoraria (institution), Non-remunerated activity/ies: Daiji Sankyo; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution), Non-remunerated activity/ies: Janssen Cilag/ J&J; Honoraria (institution), Non-remunerated activity/ies: Lilly Deutschland/ Lilly Int.; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genentics; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Riemser; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (institution), Non-remunerated activity/ies, Same disclosures for Novartis: TEVA Pharmaceuticals Ind Ltd. C.E. Geyer: Research grant / Funding (institution), Travel / Accommodation / Expenses, Medical writing support, travel/hotel expenses for non-compensated advisory board attendance: Genentech/Roche; Travel / Accommodation / Expenses, Travel/hotel expenses for Steering Committee activities: AstraZeneca; Non-remunerated activity/ies, Non-financial support, medical writing support : AbbVie; Advisory / Consultancy, Advisory Board: Celgene. C. Huang: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Novartis; Honoraria (self): EirGenix; Honoraria (self): OBI Pharma; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Daiichi Sankyo. S. Loibl: Honoraria (institution): Roche; Honoraria (institution): AbbVie; Honoraria (institution): Amgen; Honoraria (institution): AstraZeneca; Honoraria (institution): Celgene; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Seattle Genetics; Honoraria (institution): Teva; Honoraria (institution): Vifor; Honoraria (institution): PRIME; Honoraria (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. M.S. Mano: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Oncologica Brasil; Honoraria (self), Advisory / Consultancy: AstraZeneca; Shareholder / Stockholder / Stock options: Hypera; Shareholder / Stockholder / Stock options: Fleury; Shareholder / Stockholder / Stock options: Biotoscana. G. von Minckwitz: Honoraria (institution): Pfizer; Honoraria (self), Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution): Roche; Honoraria (institution): Celgene; Honoraria (institution): AstraZeneca; Honoraria (institution): Myriad Genetics; Honoraria (institution): AbbVie; Honoraria (self): Vifor Pharma. A. Brufsky: Advisory / Consultancy: Eisai; Advisory / Consultancy: Myriad Pharmaceuticals; Advisory / Consultancy: Merck; Advisory / Consultancy: Bioarray Therapeutics; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: NanoString Technologies; Advisory / Consultancy: BioTheranostics; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bayer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Celgene; Advisory / Consultancy: Agendia; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Pfizer. B. Kaufman: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy: AZ; Advisory / Consultancy: Novartis. T. Boulet: Research grant / Funding (institution): Genentech. H. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. C. Song: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. E.P. Mamounas: Honoraria (self): Genentech/Roche; Honoraria (self): Genomic Health, Inc.; Honoraria (self): Biotheranostics; Honoraria (self): Merck; Honoraria (self): Daiichi Sankyo. All other authors have declared no conflicts of interest.

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Proffered Paper – Translational research Proffered Paper session

Invited Discussant LBA15_PR and 1873O (ID 6871)

Lecture Time
09:00 - 09:15
Speakers
  • Sabine C. Linn (Amsterdam, Netherlands)
Location
Pamplona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00
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.

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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
Poster Discussion 1 – Translational research Poster Discussion session

Invited Discussant LBA17, 89PD, 90PD and 1877PD (ID 6948)

Lecture Time
09:15 - 09:35
Speakers
  • Pierre Saintigny (Lyon, France)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
08:45 - 09:45
Presidential Symposium I Proffered Paper session

Invited Discussant LBA1 and LBA2_PR (ID 7279)

Lecture Time
16:54 - 17:08
Speakers
  • Ana Oaknin (Barcelona, Spain)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
16:30 - 18:20
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.

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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.

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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.

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Presidential Symposium III Proffered Paper session

Invited Discussant LBA10_PR and LBA11 (ID 7285)

Lecture Time
16:54 - 17:09
Speakers
  • Ian Chau (Sutton, Surrey, United Kingdom)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
16:30 - 18:15