Abstract 387MO
Background
We investigated the prognostic and predictive values of tumour mutation profiles determined by next-generation sequencing (NGS) and circulating tumour cell (CTC) detection.
Methods
RAS wild-type (wt) unresectable metastatic colorectal cancer (mCRC) patients (pts) with controlled disease after FOLFIRI + cetuximab (8 cycles) were randomized to receive maintenance with bi-weekly cetuximab alone or observation until disease progression. Tumour samples were centrally analysed by NGS using the AmpliSeq™ Colon and Lung Panel v2 and CTC (Cellsearch®) were assessed at baseline and during therapy. Mutation profiles and CTC counts were analysed according to objective response rate (ORR) before randomisation and progression-free survival (PFS) from randomization (in the ITT1 and the ITT2 population, respectively).
Results
A total of 214 pts (ITT1) were included in the PRODIGE28 trial according to RAS status locally assessed in each centre, and 139 randomized (ITT2). CTC count at baseline and mutation profiles were available in 154 and 189 pts, respectively. The median number of CTC/7.5mL at baseline was 1 [range: 0-79], and ≥ 3 in 52 (34%) pts. CTC count decreased after FOLFIRI + Cetuximab in 44 out of 78 (56%) pts. Neither baseline CTC counts nor a decrease during therapy were prognostic for ORR and PFS. Among mutations analysed by NGS, none were significantly associated with ORR. Pts with a tumour activating mutation on the MAPK pathway (defined as a mutation in at least one MAPK pathway gene) (29%) had significantly lower PFS (2.3 vs 3.7 months; HR = 1.77 [1.14-2.77], p = 0.01). This effect was maintained by adjusting on primary tumour side and performance status (HR = 1.65 [1.02-2.65], p = 0.04). Test for interaction was not statistically significant (p = 0.69), indicating that MAPK pathway activation was not a predictive factor for PFS (no treatment-dependent effect on PFS).
Conclusions
This exploratory analysis suggests that patients with any tumour mutation in MAPK pathway genes are not good candidates for maintenance treatment with cetuximab or treatment interruption after first-line FOLFIRI-cetuximab.
Clinical trial identification
NCT02404935.
Editorial acknowledgement
Legal entity responsible for the study
UNICANCER.
Funding
Merck Serono S.A.S.
Disclosure
H. Blons: Financial Interests, Personal, Training: AstraZeneca; BMS; MSD. E. Francois: Financial Interests, Personal, Other, consulting, honoraria, travel, accomodations, expenses: Roche; Financial Interests, Personal, Other, honoraria, travel, accomodations, expenses: Servier; Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Other, honoraria: Amgen. M. Ben Abdelghani: Financial Interests, Personal, Other, consulting, expert testimony, travel, accomodations, expenses: Servier; Sanofi; Bayer; Financial Interests, Personal, Other, expert testimony, travel, accomodations, expenses: Roche; Ipsen; Amgen. J.M. Phelip: Financial Interests, Personal and Institutional, Other, consulting, honoraria, research funding, travel, accomodations, expenses: Merck; Roche; Sanofi; Bayer; Financial Interests, Personal, Other, consulting, honoraria, travel, accomodations, expenses: Amgen; MSD; Pierre Fabre; Servier. S. Garinet: Financial Interests, Personal, Training: Boehringer; Financial Interests, Personal, Advisory Board: Lilly. S. Gourgou: Financial Interests, Personal, Other, methodological support: Celgene; Financial Interests, Personal, Training: Roche. O. Bouche: Financial Interests, Personal, Other, honoraria as a speaker and/or in an advisory role: Merck KgaA; Roche Genentech; Bayer; Grunenthal; AstraZeneca; MSD; Amgen; Servier; Pierre Fabre. V. Boige: Financial Interests, Personal and Institutional, Other, clinical research, scientific works, consulting, travel, accomodations, expenses: Merck; Financial Interests, Personal, Other, consulting, training, travel, accomodations, expenses: Sanofi Genzyme; Bayer; Roche; Financial Interests, Personal, Other, consulting: Ipsen; Eisai; BMS; Daiichi Sankyo; Prestizia; Financial Interests, Personal, Training: Novartis; Financial Interests, Personal, Training: MSD; Financial Interests, Personal, Other, training, travel, accomodations, expenses: Amgen. All other authors have declared no conflicts of interest.
Resources from the same session
388MO - Tumor budding, an important prognostic factor in stage III colon cancer patients treated with oxaliplatin-based chemotherapy
Presenter: Debora Basile
Session: Mini oral session - Gastrointestinal tumours, colorectal
Resources:
Abstract
Slides
Webcast
389MO - Risk of bowel obstruction in patients undergoing neoadjuvant chemotherapy for high-risk colon cancer: A nested case-control matched analysis of an international, multi-centre, randomised controlled trial (FOxTROT)
Presenter: James Glasbey
Session: Mini oral session - Gastrointestinal tumours, colorectal
Resources:
Abstract
Slides
Webcast
390MO - Colorectal (CRC) cancer screening and diagnosis during the COVID-19 pandemic in Quebec, Canada
Presenter: Mustapha Tehfe
Session: Mini oral session - Gastrointestinal tumours, colorectal
Resources:
Abstract
Slides
Webcast
391MO - Impact of diabetes and metformin use on recurrence and outcome in early colon cancer (CC) patients: A pooled analysis of 3 adjuvant trials
Presenter: Elisabeth Bergen
Session: Mini oral session - Gastrointestinal tumours, colorectal
Resources:
Abstract
Slides
Webcast
Discussion 387MO, 388MO and 389MO
Presenter: Clara Montagut Viladot
Session: Mini oral session - Gastrointestinal tumours, colorectal
Resources:
Slides
Webcast
Discussion 390MO and 391MO
Presenter: Astrid Lièvre
Session: Mini oral session - Gastrointestinal tumours, colorectal
Resources:
Slides