7MO - Combined analyses of ctDNA and Immunoscore in stage III colon cancer patients: A post hoc analysis of the IDEA-France and -Greece trials

Background

Immunoscore® and Circulating tumor DNA (ctDNA) are 2 major players to improve prognostication and tailor adjuvant treatments in patients resected from a stage III colon cancer. We here analyzed both, in patients randomized in the phase III IDEA-France and HORG trials, to determine for the first time their respective prognostic value.

Methods

ctDNA was performed using a commercial tumor informed test (Signatera^TM). Multivariable analyses of time to recurrence (TTR) and overall survival (OS) in patients with ctDNA samples and in sub-groups according to Immunoscore® (high/int/low) results but also treatment duration (3/6 months) and disease risk group (high/low) were performed.

Results

Of the 554 patients with available ctDNA results, 445 were ctDNA- (80.3%) and 109 ctDNA+ (19.7%); baseline characteristics showed more T4/N2 in ctDNA+ patients (58 vs 38% p<0.01). With a median follow-up of 6.6 years, the 2-year TTR rate was 43.5% (95% CI 34.1-52.6) for ctDNA+ patients and 88.1% (95% CI 84.7-90.8) for ctDNA- patients (p<0.0001). ctDNA was confirmed as an independent prognostic marker for both TTR (adjusted HR=5.21, 95% CI 3.59-7.58, p<0.001) and OS (adjusted HR=4.74, 95% CI 3.33-6.74, p<0.001). ctDNA remained the most significant prognostic factor whatever disease stage, treatment duration and Immunoscore®. Immunoscore® was not prognostic in ctDNA+ but remained a significant prognostic tool in ctDNA- patients.

Conclusions

In this combined analysis of 2 adjuvant trials dedicated to stage III colon cancer patients, post-surgery ctDNA was found in 19.7% of them and was confirmed as a major independent prognostic marker. Immunoscore® was also confirmed as an independent prognostic marker in the 80.3% of patients that are ctDNA-.

Clinical trial identification

NCT00958737 and NCT01308066.

Legal entity responsible for the study

GERCOR.

Funding

Has not received any funding.

Disclosure

J. Taieb: Financial Interests, Personal, Invited Speaker, advisory boards: Amgen, Astellas, AstraZeneca, BMS, Merck KGaA, MSD, Novartis, Ono Pharmaceuticals, Pierre Fabre, Roche Genentech, Sanofi, Servier and Takeda. I. Souglakos: Financial Interests, Personal, Invited Speaker, advisory boards: Merck KGaA, Sanofi, Roche Genentech, MSD, BMS, Servier, Leo, AstraZeneca, Genesis Hellas, and Amgen. F. Pages: Financial Interests, Personal, Invited Speaker, advisory role: BMS, Roche, Janssen, Merck; Financial Interests, Personal, Ownership Interest: Veracyte HallioDx. C. Louvet: Financial Interests, Personal, Invited Speaker, advisory role: MSD, Halozyme, Roche, Celgene, Amgen, outside the submitted work. OB reports personal fees for speaker bureau and/or advisory role from Merck KGaA, Roche Genentech, Bayer, AstraZeneca, Grunenthal, MSD, Amgen, Servier, Pierre Fabre. S. Sharma: Financial Interests, Personal, Stocks/Shares, employee: Natera. T. André: Financial Interests, Personal, Invited Speaker, advisory role: AbbVie, Astellas, Aptitude Health, Bristol Myers Squibb, Gritstone Oncology, Gilead, GSK, Merck & Co. Inc., Nordic Oncology, Seagen, Servier, Takeda and honoraria from Bristol Myers Squibb, GSK, Merck & Co. Inc., Merck Serono, Ro. P. Laurent Puig: Financial Interests, Personal, Invited Speaker, advisory role: Amgen, BMS, Merck Serono, Roche, MSD; personal fees from AstraZeneca, Boehringer Ingelheim, Biocartis, Sanofi Fabre. All other authors have declared no conflicts of interest.