Found 19 Presentations For Request "LBA3"

Proffered Paper 2 – Gastrointestinal tumours, colorectal Proffered Paper session

LBA34 - MIRACLE: Green tea extract versus placebo for the prevention of colorectal adenomas: A randomized, controlled trial (ID 1890)

Presentation Number
LBA34
Lecture Time
09:30 - 09:45
Speakers
  • Thomas Seufferlein (Ulm, Germany)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
08:30 - 10:00

Abstract

Background

Prevention of colorectal adenomas (CA) is likely to prevent colorectal cancer (CRC). Nutri- or chemoprevention of CRC is not yet established. NSAIDs show some benefit but also increase the bleeding risk. Agents with a more favourable benefit/risk ratio are desirable. Preclinical and small clinical trials suggest that epigallocatechingallate (EGCG), a major polyphenol in green tea, has a good safety profile and antineoplastic effects in the large bowel, but there are no data from large trials. MIRACLE enrolled 1001 patients to examine the effect of a three year intake of ECGC on the recurrence of CA after polypectomy.

Methods

Double-blinded, placebo-controlled trial, 41 recruiting German centers, recruitment 12/2011-6/2015. Patients aged 50-80 years who underwent polypectomy within the last 6 months and tolerated EGCG well during a one month run-in were randomized to standardized decaffeinated EGCG (150 mg bid) or placebo for 3 years. Primary endpoint: Incidence of metachronous CA at the 3 year follow-up colonoscopy. Secondary endpoints: Occurrence, number, localization, size, histological subtype of CA, frequency of CRC and biomarker. Strata: Study center and intake of low-dose aspirin (≤100 mg/d).

Results

Clinical parameters were well balanced between the groups. Primary endpoint was analysed in the modified ITT set (modITT; n = 309 patients in EGCG, n = 323 in placebo group giving informed consent and undergoing 3 year follow up colonoscopy in the requested time frame). n = 102 patients in the EGCG and n = 103 in the placebo group were excluded due to missing follow up colonoscopy. Incidence of one or more CA after 3 year of placebo or EGCG 150 mg bid was 55.7 % and 51.1%, respectively (one sided adj. P = 0.077, adj. RR 0.904) in the modITT. In the per protocol set constituting all modITT patients completing the study without major protocol violations the respective figures were 54.3 % in the placebo and 48.3% in the EGCG group (one sided adj. P = 0.058, adj. RR 0.883). There were no safety issues and no major differences in AEs between EGCG and placebo during the randomized phase.

Conclusions

300 mg EGCG per day was well tolerated and showed a trend towards a preventive effect on CA in the large bowel though not statistically significant.

Clinical trial identification

NCT01360320.

Legal entity responsible for the study

Martin-Luther-Universität Halle-Wittenberg, Germany.

Funding

German Cancer Aid (Stiftung Deutsche Krebshilfe).

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion – Gastrointestinal tumours, colorectal Poster Discussion session

LBA35 - Phase II study of pertuzumab and trastuzumab-emtansine (T-DM1) in patients with HER2-positive metastatic colorectal cancer: The HERACLES-B (HER2 Amplification for Colo-rectaL cancer Enhanced Stratification, cohort B) trial (ID 3857)

Presentation Number
LBA35
Lecture Time
15:00 - 15:00
Speakers
  • Andrea Sartore-Bianchi (Milan, Italy)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
15:00 - 16:15

Abstract

Background

HER2 amplification (HER2+) is a therapeutic target for 2% (unselected)-6% (RAS wild-type) metastatic colorectal cancer (mCRC). In the HERACLES-A Trial of trastuzumab and lapatinib (Lancet Oncology, 2016), HER2+ KRAS wild-type mCRC patients achieved an overall objective response rate (CR+PR = ORR) of 30%. Based on this result and on preclinical trials, we activated HERACLES-B, evaluating a targeted chemotherapy precision approach by combining pertuzumab with T-DM1.

Methods

HERACLES-B is an open-label phase II trial in RAS/BRAF wild-type HER2+ mCRCs (as defined in Valtorta et al, 2015). ORR and Progression-Free Survival (PFS) are the primary and secondary end-points, respectively. With a Fleming/Hern design (H0=ORR 10%; α = 0.05; power=0.85), 7 OR/30 were required to demonstrate an ORR ≥30% (H1). Main inclusion criteria were: PS 0-1, progression after 5FU, oxaliplatin, irinotecan, and anti-EGFR containing regimens. Pertuzumab was dosed at 840 mg iv load, followed by 420 mg iv q3 weeks and T-DM1 at 3.6 mg/Kg q3 weeks. NGS-based molecular analyses of tumor tissue/plasma were performed.

Results

From 8/2016 to 3/2018, 30 patients were enrolled, treated and evaluable for efficacy. Patients received a median of 3 prior regimens. Data lock and centralized radiological revision were completed by 30/7/2019. ORR was 10% [95% CI: 0-28] and stable disease (SD) 70% [95% CI: 50-85]. Median PFS was 4.8 mos. [95% CI: 3.6-5.8]. Higher HER2 IHC score (3+ vs 2+) was associated with objective response/SD ≥4 mos. [p = 0.03]. Drug-related G3 adverse events were observed only in 2 patients (thrombocytopenia); G ≤ 2 events in 84% of cycles (N = 296), mainly nausea and fatigue.

Conclusions

Although HERACLES-B did not reach its primary endpoint, disease control was achieved in 80% of patients with a median PFS of 4.8 mos. that is superimposable to the 4.2 mos. achieved in the positive HERACLES-A trial. While the ORR could have been weakened by the lower trastuzumab dose delivered with T-DM1, the retained favorable PFS might be due the combined ‘broad-brush’ effect of emtansine and the synergy with pertuzumab. Preliminary molecular results will be presented.

Clinical trial identification

EudraCT: 2012-002128-33.

Legal entity responsible for the study

Fondazione del Piemonte per l’Oncologia IRCC di Candiolo.

Funding

Fondazione Piemontese per l’Oncologia - FPO funded by Associazione Italiana per la Ricerca sul Cancro (AIRC). Roche provided pertuzumab and T-DM1 for free.

Disclosure

A. Sartore-Bianchi: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Sanofi. A. Amatu: Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer; Advisory / Consultancy: Amgen. A. Ardizzoni: Advisory / Consultancy: Roche. L. Trusolino: Research grant / Funding (self): Symphogen; Research grant / Funding (self): Merus; Research grant / Funding (self): Servier; Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Merck KGaA. S. Siena: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: CheckMab; Advisory / Consultancy: Celgene; Advisory / Consultancy: Clovis; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche-Genentec; Advisory / Consultancy: Seattle Genetics. All other authors have declared no conflicts of interest.

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Proffered Paper 1 – Gastrointestinal tumours, colorectal Proffered Paper session

LBA30_PR - Analysis of circulating tumour DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: Prognostic and predictive value for adjuvant treatment duration (ID 5478)

Presentation Number
LBA30_PR
Lecture Time
14:45 - 15:00
Speakers
  • Julien Taieb (Paris, France)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
14:45 - 16:15

Abstract

Background

ctDNA has been recently suggested as a major prognostic factor in resected stage II and III colon cancer patients (pts)1,2. Its predictive value for adjuvant treatment intensity or duration is currently unknown. We have analyzed here ctDNA from pts enrolled in the IDEA-FRANCE trial3, its prognostic value and its predictive value for treatment duration (3 or 6 months).

Methods

ctDNA was tested by using the detection of 2 methylated markers (WIF1 and NPY) by digital droplet PCR accordingly to a method developed and validated for colorectal cancer 4-6. Comparisons for pts and tumour characteristics and DFS will be done between the ctDNA tested pts and the full study population and between ctDNA positive and negative pts. DFS has been analyzed in the 6 and 3M treatment arms according to ctDNA results. Subgroup analyses for high- and low-risk pts were pre-planned.

Results

Of the 1345/2010 pts that consented to the IDEA translational research program, with available blood sample for ctDNA testing, 805 have been sampled before chemotherapy start and fully analyzed. More PS 0 (77% vs 71%) and more T4 and/or N2 (28% vs 23%) were observed in the 805 pts studied here than in the 1205 pts left. 696 pts were found ctDNA- and 109 ctDNA + (13.5%). ctDNA+ pts were more often T4, poorly differentiated and with tumour perforation. 2-year DFS was 64% vs 82% in ctDNA+ and – pts, respectively (HR :1.75 (95%CI 1.25-2.45) p = 0.001). In multivariate analysis including Age, Gender, MSI, perforation, T stage, N stage and treatment arm, ctDNA was confirmed as an independent prognostic marker (adj.HR: 1.85 (95%CI 1.31 to 2.61) p < 0.001). Adjuvant treatment for 6 months was superior to 3 months in both ctDNA– (HR :0.69 (95%CI 0.52 to 0.93) p = 0.015) and ctDNA+ pts (HR: 0.50 (95%CI 0.27 to 0.95) p = 0.033). Interestingly ctDNA+ pts treated 6 months had a similar prognosis to ctDNA- pts treated 3 months.

Conclusions

In this first ctDNA assessment on a large series coming from a phase III clinical trial we found 13.5% of pts with ctDNA post-surgery. ctDNA was confirmed as an independent prognostic marker. In this series, 6 months of treatment seems better in both ctDNA+ and- pts. [1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92. [2]Schøler LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. [3] André T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477. [4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139. [5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425. [6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219.

Clinical trial identification

NCT00958737.

Editorial acknowledgement

[1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92.

[2]Schøler LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445.

[3] André T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477.

[4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139.

[5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425.

[6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219.

Legal entity responsible for the study

Gercor-Prodige.

Funding

Clinical trial: INCa, GERCOR; Translational project: ARC (Association de Recherche contre le Cancer, Paris, France).

Disclosure

J. Taieb: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: pierre fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi. D. Vernerey: Honoraria (self), Advisory / Consultancy: HalioDX; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Janssen. J. Bennouna: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

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Presidential Symposium I Proffered Paper session

LBA3 - VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC) (ID 2772)

Presentation Number
LBA3
Lecture Time
17:08 - 17:20
Speakers
  • Robert L. Coleman (Houston, TX, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
16:30 - 18:20

Abstract

Background

This phase III randomized placebo (PL) controlled multinational trial evaluated whether progression-free survival (PFS) is increased when V is added to front-line carboplatin and paclitaxel (CP) and continued as maintenance in newly diagnosed HGSC pts considering BRCA mutations (m), homologous recombination deficiency (HRD), and neoadjuvant chemotherapy (NACT) utilization.

Methods

Previously untreated Stage III-IV HGSC pts were to receive 6 cycles (21-d interval) of CP using 3-wkly or wkly paclitaxel, following primary cytoreduction or NACT with interval cytoreduction. V or PL was administered during CP (150 mg BID PO) and as maintenance (400 mg BID for 30 cycles). Randomization was 1:1:1, stratified by Stage III vs IV, residual disease and regimen, region, and gBRCA status: Arm 1: CP + PL then PL maintenance Arm 2: CP + V then PL maintenance Arm 3: CP + V then V maintenance Primary endpoints were PFS (Kaplan-Meier) in Arm 3 vs 1 using hierarchical testing in BRCAm, HRD (incl. BRCAm), and whole populations by log-rank tests. Secondary endpoints were PFS (Arm 2 vs 1), overall survival, and disease related symptom scores. Germline and tissue BRCAm and HRD were determined by central testing.

Results

1140 pts were enrolled with 26% in BRCAm and 55% in HRD populations. Efficacy results summarized in Table. Relative CP dose intensities were similar between arms. Grade 3-4 adverse events (AE; Arm 3 vs 1) were similar during CP with the exception of thrombocytopenia (27% vs 8%); during maintenance, any grade 3-4 AE was higher for V treatment (45% vs 32%) but serious AEs were similar (17% vs 19%).

LBA3

Population
BRCAm
HRD
Whole
Arm 3 n = 108Arm 1 n = 92Arm 3 n = 214Arm 1 n = 207Arm 3 n = 382Arm 1 n = 375
Median PFS (months)34.722.031.920.523.517.3
PFS HR (95% CI) P value0.44 [0.28, 0.68] < 0.0010.57 [0.43, 0.76] < 0.0010.68 [0.56, 0.83] < 0.001

BRCAm, BRCA mutated; HRD, homologous recombination deficient; HR, hazard ratio; P value by stratified log-rank test; PFS, progression-free survival.

Conclusions

V added to front-line CP and continued as monotherapy maintenance significantly extended PFS in all women with newly diagnosed HGSC without selection according to BRCAm or HRD status, or response to CP. Observed toxicities were consistent with known V safety profile.

Clinical trial identification

NCT02470585.

Editorial acknowledgement

Medical writing support was provided by Ana Mrejeru, Ph.D., of AbbVie.

Legal entity responsible for the study

AbbVie.

Funding

AbbVie.

Disclosure

R.L. Coleman: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Clovis Oncology; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (self): Esperance; Advisory / Consultancy: NCCN; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca/MedImmune; Advisory / Consultancy: Genmab; Advisory / Consultancy: GamaMabs Pharma; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (self): OncoMed; Advisory / Consultancy: Sotio; Advisory / Consultancy: Oncolytics; Advisory / Consultancy: AbbVie/Stemcentrx; Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Research grant / Funding (self), Travel / Accommodation / Expenses: Array Biopharma; Travel / Accommodation / Expenses: Research to Practice; Travel / Accommodation / Expenses: GOG; Travel / Accommodation / Expenses: Sotio; Travel / Accommodation / Expenses: Vaniam Group; Research grant / Funding (self): Johnson & Johnson; Research grant / Funding (self): Abbott/AbbVie. G.F. Fleming: Research grant / Funding (self): Corcept Therapeutics; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Genentech; Research grant / Funding (self): Tesaro; Research grant / Funding (self): Syndax; Research grant / Funding (self): Forty Seven; Research grant / Funding (self): Iovance; Research grant / Funding (self): Syros; Research grant / Funding (self): Astex; Research grant / Funding (self): Merck. K.D. Steffensen: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AbbVie. M. Friedlander: Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Takeda; Research grant / Funding (self): BeiGene. A. Okamoto: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Chugai; Honoraria (self): MSD; Research grant / Funding (self): Kaken; Research grant / Funding (self): Mochida; Research grant / Funding (self): Kissei; Research grant / Funding (self): Pfizer. K. Moore: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Immunogen; Advisory / Consultancy, Research grant / Funding (institution): Advaxis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Non-remunerated activity/ies: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Janssen Oncology; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Aravive; Advisory / Consultancy: Samumed; Advisory / Consultancy: OncoMed; Advisory / Consultancy: Pfizer/EMD Serono ; Advisory / Consultancy: Eisai; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Lilly Foundation; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Verastern; Research grant / Funding (institution): Agenus; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Forty Seven; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Novogen. N. Ben-Baruch: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Research grant / Funding (self): AbbVie. T.L. Werner: Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): AstraZeneca. A. Oaknin: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Pharmamar; Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Immunogen ; Advisory / Consultancy: Genmab. J. Nam: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Zeria Pharmaceutical Co.. C.A. Leath III: Honoraria (self), Research grant / Funding (institution): Mateon Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Celsion; Advisory / Consultancy: Unleash Immuno Oncolytics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Syros; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Eisai. S. Nicum: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. D. Cella: Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: PledPharma; Advisory / Consultancy: Puma Biotechnology; Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Shareholder / Stockholder / Stock options: FACIT.org; Research grant / Funding (institution): Genentech. D.M. Sullivan: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. P.J. Ansell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. M. Dinh: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. C. Aghajanian: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Mateon Therapeutics; Advisory / Consultancy: Immunogen; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cerulean Pharma; Advisory / Consultancy: Eisai/Merck. M.A. Bookman: Non-remunerated activity/ies, Member, international protocol steering committee (AbbVie GOG3005): AbbVie; Non-remunerated activity/ies, protocol steering committee: Genentech-Roche; Non-remunerated activity/ies, protocol steering committee: ARAVIVE; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Merck; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

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Proffered Paper 1 – Gastrointestinal tumours, non-colorectal Proffered Paper session

Invited Discussant LBA38_PR and LBA39 (ID 6697)

Lecture Time
14:30 - 14:45
Speakers
  • Arndt Vogel (Hannover, Germany)
Location
Madrid Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
27.09.2019
Time
14:00 - 15:30
Proffered Paper 1 – Gastrointestinal tumours, colorectal Proffered Paper session

Invited Discussant LBA30_PR and 522O (ID 6681)

Lecture Time
15:15 - 15:30
Speakers
  • Clara Montagut Viladot (Barcelona, Spain)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
14:45 - 16:15
Poster Discussion – Gastrointestinal tumours, colorectal Poster Discussion session

LBA36 - Randomized phase II study of CAPTEM versus FOLFIRI in RAS mutated, MGMT methylated metastatic colorectal cancer (mCRC): Final analysis, tumour biomarkers and methylated ctDNA (ID 5756)

Presentation Number
LBA36
Lecture Time
15:00 - 15:00
Speakers
  • Filippo Pietrantonio (Milan, Italy)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
15:00 - 16:15

Abstract

Background

In non-randomized trials, temozolomide (TMZ) has shown activity in about 10% of pts with chemorefractory mCRC bearing MGMT methylation.

Methods

This multicenter, randomized phase II trial investigated PFS superiority of second-line CAPTEM (Arm A) vs FOLFIRI (arm B) in RAS mutated mCRC pts with MGMT methylation centrally confirmed by MSP. Eligible pts had ECOG PS 0-1, measurable disease, and failed prior oxaliplatin-based therapy. Randomization to arm A (capecitabine 750 mg/sqm b.i.d. days 1-14 plus TMZ 75 mg/sqm b.i.d. days 10-14 q28) or B was stratified according to time elapsed from the start of oxaliplatin-based therapy and PD (</≥9 months); prior bevacizumab. A one-sided log-rank test with an overall sample size of 82 pts (41 per arm) achieved 90% power at 5% significance level to detect PFS increase from 2 to 4 mos. Secondary endpoints: safety, QoL, OS, ORR. Exploratory biomarkers: MGMT IHC; methylBEAMing (MB) in tumor and ctDNA.

Results

A total of 86 pts were randomized (43 per arm). After a median follow-up of 30.5 months (IQR 12.2-36.3), 79 disease PFS events occurred. PFS and OS were 3.5 (2.0-5.0) and 9.5 (8.2-25.8) months in arm A vs 3.5 (2.3-6.1) and 10.6 (8.5-20.8) in arm B (HR = 1.86 [0.82-1.72] and HR = 0.97 [0.58-1.61]), respectively. ORR and DCR were 11.6% and 53.5% in both arms. Grade ≥3 treatment-related adverse events had higher incidence in arm B versus A (47.6% vs 16.3%), and quality of life was significantly worse in arm B. In the subgroup with negative MGMT IHC expression, there were no significant differences between the two arms in terms of activity and efficacy endpoints, whereas in pts with positive MGMT IHC expression CAPTEM regimen was associated with significantly inferior outcomes in terms of PFS (2.0 vs 3.5 mos; HR = 2.08 [1.02-4.21]), OS (5.7 vs 10.6 mos; OR = 1.07 [0.39-2.93]) and DCR (15.4 vs 56.5%; OR = 0.23 [0.04-0.99]), interaction test p = 0.125, 0.732, 0.028. Predicting outcomes with MB was more accurate when using ctDNA vs tumor DNA.

Conclusions

TMZ-based treatment should be investigated by a phase III trial, ideally conducted in patients with MGMT methylated/MGMT IHC negative tumors.

Clinical trial identification

NCT02414009.

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale Tumori di Milano.

Funding

Fondazione IRCCS Istituto Nazionale Tumori di Milano.

Disclosure

F. Pietrantonio: Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Merck-Serono; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Servier. F. Morano: Honoraria (self): Servier Italia SpA . S. Lonardi: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Merk-Serono; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Bristol-Mayers-Squibb. L. Rimassa: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Gilead; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Sirtex Medical; Honoraria (self), Advisory / Consultancy: Italfarmaco; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Baxter; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: ArQule; Honoraria (self), Advisory / Consultancy: Xelixis; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Eisai. A. Sartore-Bianchi: Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Merk-Serono; Honoraria (self), Advisory / Consultancy: Roche. M. Di Bartolomeo: Advisory / Consultancy: Lilly; Advisory / Consultancy: Servier; Travel / Accommodation / Expenses: Roche. F.G.M. De Braud: Honoraria (self), Advisory / Consultancy: TizianaLife Sciences; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Pharm Research Associated; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Octimet Oncology; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: Teofarma; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy: EMD Serono; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Gentili; Speaker Bureau / Expert testimony: Fondazione Menarini. All other authors have declared no conflicts of interest.

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Proffered Paper 1 – Gastrointestinal tumours, colorectal Proffered Paper session

LBA31 - Bevacizumab plus chemotherapy versus chemotherapy alone as first-line treatment for patients with RAS mutant unresectable colorectal liver-limited metastases: A single center randomized control trial (ID 4839)

Presentation Number
LBA31
Lecture Time
15:45 - 16:00
Speakers
  • Jianmin Xu (shanghai, China)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
14:45 - 16:15

Abstract

Background

To assess the effects of bevacizumab plus chemotherapy as first-line treatment for RAS mutant unresectable colorectal liver metastases (CLMs).

Methods

From June 2013 to December 2017, patients with RAS mutant unresectable liver-limited metastases from colorectal cancer were randomly assigned to receive chemotherapy (mFOLFOX6 [modified fluorouracil, leucovorin,and oxaliplatin]) plus bevacizumab (arm A) or chemotherapy alone (arm B). The resectability of liver metastases was determined by a local multidisciplinary team. The primary end point was the rate of patients converted to resection for liver metastases. Secondary end points included tumor response, survival and toxicity. Block randomization method was used.

Results

The intent-to-treat population comprised 241 patients. 121 patients were randomly assigned to arm A and 120 to arm B. For all patients, 35.7% (86/241) had right-sided colon cancer; 47.3% (114/241) had primary tumour resection before randomization; 86.3% (208/241) had liver metastases more than three; 33.2 (80/241) with the diameter of liver metastases more than 5 cm; 78.4% (189/241) were bilobar metastases. The median follow-up time was 37.0 months for all patients. The R0 resection rates for liver metastases were 22.3% (27 of 121 patients) in arm A and 5.8% (7 of 120 patients) in arm B, with significant difference (P < 0.01). Patients in arm A had significantly better objective response rates (54.5% v 36.7%; P < 0.01), median PFS (9.5 v 5.6 months; P < 0.01) and median OS (25.7 v 20.5 months; P = 0.03) compared with those in arm B. Addition of bevacizumab was associated with more frequent proteinuria(9.9% v 3.3%; P = 0.04) and hypertension ( 8.3% v 2.5%; P < 0.05).

Conclusions

For patients with initially unresectable RAS mutant CLMs, bevacizumab combined with chemotherapy improved the resectability of liver metastases and improved response rates and survival compared with chemotherapy alone.

Clinical trial identification

NCT01972490.

Legal entity responsible for the study

Zhongshan Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper 1 – Gastrointestinal tumours, non-colorectal Proffered Paper session

LBA38_PR - CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC) (ID 6572)

Presentation Number
LBA38_PR
Lecture Time
14:00 - 14:15
Speakers
  • Thomas Yau (Hong Kong, Pokfulam, Hong Kong PRC)
Location
Madrid Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
27.09.2019
Time
14:00 - 15:30

Abstract

Background

SOR is approved as 1L therapy for pts with aHCC, but there is still an unmet need to prolong survival and improve tolerability. This phase III study compared clinical efficacy and safety of NIVO with SOR as 1L therapy in pts with aHCC.

Methods

Systemic therapy–naive pts aged ≥18 years with aHCC were randomized 1:1 to NIVO (240 mg IV Q2W) or SOR (400 mg oral BID). Primary endpoint was overall survival (OS). Additional endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review per RECIST v1.1, efficacy by tumor programmed death ligand 1 (PD-L1) expression, and safety.

Results

743 pts with aHCC were randomized to NIVO (n = 371) or SOR (n = 372) with minimum follow-up of 22.8 months at data cutoff. OS did not meet the predefined threshold of statistical significance (HR 0.84, P = 0.0419). Median OS (mOS) was 16.4 mo for NIVO and 14.7 mo for SOR (HR 0.85 [95% CI: 0.72–1.02]; P = 0.0752). Clinical benefit was observed across predefined subgroups, including hepatitis infection status, presence of vascular invasion and/or extrahepatic spread, and region (Asia vs non-Asia). ORR was 15% for NIVO (14 pts with complete response [CR]) and 7% for SOR (5 pts with CR; Table). Grade 3/4 treatment-related adverse events were reported in 81 pts (22%) in the NIVO arm and 179 pts (49%) in the SOR arm and led to discontinuation in 16 (4%) and 29 (8%) pts, respectively. No new safety signals were observed with NIVO. 140 pts (38%) in the NIVO arm and 170 pts (46%) in the SOR arm received subsequent therapy. Additional OS analyses and patient-reported outcomes will be presented to support the benefit of NIVO.

Efficacy results

NIVOSOR
n = 371n = 372
Median OS (95% CI), mo16.4 (13.9–18.4)14.7 (11.9–17.2)
12-mo OS rate, % (95% CI)59.7 (54.4–64.6)55.1 (49.8–60.1)
24-mo OS rate, % (95% CI)36.8 (31.8–41.8)33.1 (28.3–38.0)
Median PFS, mo (95% CI)3.7 (3.1–3.9)3.8 (3.7–4.5)
ORR, n (%)57 (15)26 (7)
BOR, n (%)
Complete response14 (4)5 (1)
Partial response43 (12)21 (6)
ORR by baseline tumor PD-L1 expression, n/n (%)
PD-L1 ≥1%20/71 (28)6/64 (9)
PD-L1 <1%36/295 (12)20/300 (7)

Conclusions

Though the primary endpoint of OS did not achieve statistical significance vs SOR, NIVO showed clinically meaningful improvements in OS, ORR, and CR rate as 1L treatment for aHCC. NIVO demonstrated a favorable safety profile consistent with previous reports.

Clinical trial identification

NCT02576509.

Editorial acknowledgement

Writing and editorial assistance was provided by Andrea L. Hammons of Parexel International (Waltham, MA, USA) and funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

T. Yau: Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb. R.S. Finn: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Honoraria (self), Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Roche/ Genentech. A. Cheng: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Merck Sharp Dohme; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin; Speaker Bureau / Expert testimony: Amgen Taiwan; Advisory / Consultancy: Ispen; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis. P. Mathurin: Honoraria (self), Speaker Bureau / Expert testimony: Ipsen; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: Bayer Healthcare ; Honoraria (self), Speaker Bureau / Expert testimony: AbbVie; Honoraria (self), Speaker Bureau / Expert testimony: Gilead; Honoraria (self), Speaker Bureau / Expert testimony: Servier; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi. J. Edeline: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony: IPSEN; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Travel / Accommodation / Expenses: Amgen. M. Kudo: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Ono; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medico’s Hirata; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): EA Pharma; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Gilead. J.J. Harding: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Exelexis; Honoraria (self), Speaker Bureau / Expert testimony: Elly Lilly ; Honoraria (self), Speaker Bureau / Expert testimony: CytomX; Honoraria (self), Speaker Bureau / Expert testimony: QED. P. Merle: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): IPSEN; Advisory / Consultancy: Eisai; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: AstraZeneca. O. Rosmorduc: Honoraria (self): Bayer; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Sirtex; Honoraria (self): Eisai. L. Wyrwicz: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Beigene; Research grant / Funding (self): Eisai. E. Schott: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Bayer. S.P. Choo: Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy: Sirtex; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen. R.K. Kelley: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Honoraria (self), Speaker Bureau / Expert testimony, IDMC membership: Genentech/Roche; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): AstraZeneca. D. Begic: Full / Part-time employment: Bristol-Myers Squibb. J. Neely: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. J. Anderson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. B. Sangro: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: BTG; Advisory / Consultancy: H3 Biomedicine; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Onxeo; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Advisory / Consultancy: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Terumo. All other authors have declared no conflicts of interest.

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Proffered Paper 1 – Gastrointestinal tumours, colorectal Proffered Paper session

Invited Discussant 523O and LBA31 (ID 6682)

Lecture Time
16:00 - 16:15
Speakers
  • Claus-Henning Koehne (Oldenburg, Germany)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
14:45 - 16:15
Poster Discussion – Supportive and palliative care Poster Discussion session

Invited Discussant LBA37, LBA90 and 1758PD (ID 6938)

Lecture Time
15:20 - 15:35
Speakers
  • Anton Snegovoy (Moscow, Russian Federation)
Location
Bilbao Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
15:00 - 16:00
Proffered Paper 2 – Gastrointestinal tumours, colorectal Proffered Paper session

LBA32 - Encorafenib plus cetuximab with or without binimetinib for BRAF V600E–mutant metastatic colorectal cancer: Expanded results from a randomized, 3-arm, phase III study vs the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC) (ID 4491)

Presentation Number
LBA32
Lecture Time
08:30 - 08:45
Speakers
  • Josep Tabernero (Barcelona, Spain)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
08:30 - 10:00

Abstract

Background

Encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) significantly improved overall survival (OS, HR:0.52, P < 0.0001) and objective response rates (ORR, 26% vs 2%, P < 0.0001) in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) compared with current standard of care. This analysis focuses on the triplet ((ENCO+CETUX+BINI) and doublet (ENCO+CETUX) arms.

Methods

The BEACON CRC study was a randomized, 3-arm, phase 3 study which evaluated triplet or doublet vs. investigator’s choice of irinotecan or FOLFIRI + CETUX in 665 pts with BRAFV600E mCRC. The triplet vs doublet efficacy comparison was a secondary endpoint (not formally powered). Analyses included efficacy (OS, ORR, depth of response, and progression-free survival [PFS]), multivariate modeling, safety, and quality of life (QOL) assessments (EORTC QOL Questionnaire (QLQ C30), Functional Assessment of Cancer Therapy Colon Cancer, EuroQol 5D 5L, and Patient Global Impression of Change).

Results

224 and 220 pts were randomized to triplet and doublet, respectively. Median overall survival for triplet and doublet was 9.0 (95%CI: 8.0, 11.4) and 8.4 months (95%CI: 7.5, 11.0), respectively (HR:0.79 [95%CI: 0.59, 1.06]). ORR was 26% (95%CI: 18%, 35%) for triplet and 20% (95%CI: 13%,29%) for doublet. For pts with 1 prior therapy, ORR was 34% (95%CI: 23, 47) for triplet and 22% (95%CI: 14, 33) for doublet. Waterfall plots indicated that depth of response favored triplet. Grade 3+ adverse events (AE) were 58% in triplet and 50% in doublet. Rates of discontinuation due to an AE were similar (triplet: 7%; doublet: 8%), with median relative dose intensity maintained for both arms. There were no differences in QOL across 4 instruments. Some toxicities occurred less frequently with the triplet.

Conclusions

In BEACON CRC, triplet and doublet showed encouraging activity in BRAFV600E mCRC. Data suggest that the triplet offers improved efficacy vs doublet with some additional manageable toxicity and no impact on overall QOL. Further follow-up will better define the relative benefits of the regimens.

Clinical trial identification

NCT02928224.

Editorial acknowledgement

Editorial assistance was provided by JD Cox and Mayville Medical Communications, with funding from Array Biopharma.

Legal entity responsible for the study

Array BioPharma Inc.

Funding

Array BioPharma Inc.

Disclosure

J. Tabernero: Advisory / Consultancy: Bayer; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Taiho; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Peptomyc; Advisory / Consultancy: Rafael Pharmaceuticals; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Chugai Pharma; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Merus; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BeiGene. A. Grothey: Honoraria (self): Elsevier; Honoraria (self): Aptitude Health; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boston Biomedical; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Array BioPharma; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eisai; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Boehringer Ingelheim. E. Van Cutsem: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Merck. R. Yaeger: Research grant / Funding (institution), Travel / Accommodation / Expenses: Array BioPharma; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony: Sysmex; Research grant / Funding (institution): Symphogen; Licensing / Royalties: Biocartis. H. Wasan: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck KGaA; Honoraria (self), Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Honoraria (self): Array BioPharma; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self): Genentech; Honoraria (self), Advisory / Consultancy: ERYTECH Pharma; Advisory / Consultancy: Roche; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): MSD. T. Yoshino: Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Sumitomo Dainppon; Research grant / Funding (institution): GSK. J. Desai: Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Bionomics; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy: Ignyta; Research grant / Funding (institution): Roche; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Ipsen. F. Ciardiello: Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Ipsen. N. Steeghs: Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Incyte. H. Arkenau: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution), Travel / Accommodation / Expenses: Iovance; Full / Part-time employment: SCRI. A. Gollerkeri: Full / Part-time employment: Pfizer Inc.. M. Pickard: Full / Part-time employment: Pfizer Inc.. K. Maharry: Full / Part-time employment: Pfizer Inc.. J.L. Christy-Bittel: Full / Part-time employment: Pfizer Inc.. L. Anderson: Full / Part-time employment: Pfizer Inc.. S. Kopetz: Shareholder / Stockholder / Stock options: MolecularMatch; Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Navire ; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Advisory / Consultancy: Merck; Advisory / Consultancy: Karyopharm; Advisory / Consultancy: Amal Therapeutics; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Holy Stone; Advisory / Consultancy, Research grant / Funding (institution): Biocartis; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Guardian Health; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): MedImmune. All other authors have declared no conflicts of interest.

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