Abstract 1866
Background
In metastatic colorectal cancer (mCRC), circulating tumour DNA (ctDNA) monitoring can be used to genotype tumors and track clonal evolution. We investigated the clearance of RAS mutated clones under chemotherapy pressure by ctDNA analysis in patients with a RAS mutated mCRC.
Methods
Patients with a RAS mutated tumour included in the prospective PLACOL study, were monitored for ctDNA. Analyzes were based on optimized targeted next generation sequencing and/or droplet-based digital PCR (ddPCR). For plasma samples without detectable mutations, we tested the methylation status of WIF1 and NPY genes using methylation-ddPCR (met-ddPCR) to validate the presence of ctDNA.
Results
Among the 36 patients with positive plasma samples for RAS mutations at inclusion, 28 (77.8%) remained RAS positive at disease progression, and 8 (22.2%) became negative. Subsequent met-ddPCR for methylated markers showed that only 2 out of the 8 patients with RAS negative plasma had detectable ctDNA at progression. Therefore, only two samples among 36 were confirmed for clearance of RAS mutation in our series.
Conclusions
This study suggests that the clearance of RAS mutations in patients treated by chemotherapy for a RAS mutated mCRC is a rare event. Monitoring tumor mutations in plasma samples should be combined with a strict control of the presence of ctDNA. The therapeutic impacts of RAS clearance need to be further explored.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The Ministère de l’Enseignement Supérieur et de la Recherche, the Université Paris-Descartes, the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut National du Cancer (INCA, n° 2009-1-RT-03-US-1 and 2009-RT-03-UP5-1), the Association pour la recherche contre le cancer (ARC, no. SL220100601375), the Agence Nationale de la Recherche (ANR Nanobiotechnologies; no. ANR-10-NANO-0002-09), the SIRIC CARPEM, the ligue nationale contre le cancer (LNCC, Program “Equipe labelisée LIGUE”; no. EL2016.LNCC/VaT) and Advanced Merieux Research Grant and canceropole funding (no. 2011-1-LABEL-UP5-2).
Disclosure
H. Blons: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Amgen; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Pfizer. V. Taly: Advisory / Consultancy: Servier; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Raindance Technologies. W. Shu-Fang: Research grant / Funding (institution): Servier. S. Pernot: Advisory / Consultancy: Amgen; Advisory / Consultancy: Sanofi. J. Taieb: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sirtex; Advisory / Consultancy, Speaker Bureau / Expert testimony: Shire; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre. P. Laurent-Puig: Advisory / Consultancy: Amgen; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly. A. Zaanan: Advisory / Consultancy: Amgen; Advisory / Consultancy: Baxter; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: MSD; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Advisory / Consultancy: Servier. All other authors have declared no conflicts of interest.
Resources from the same session
1109 - First Canadian Interim Analysis from the Phase IIIb CompLEEment-1 Ribociclib + Letrozole HR+ HER2- Advanced Breast Cancer Trial
Presenter: Cristiano Ferrario
Session: Poster Display session 2
Resources:
Abstract
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract