A meta-analysis of individual patient data from the ACCENT database showed that the combination of oxaliplatin plus fluoropyrimidine (FP) should be considered as a standard-of-care diagnostic treatment for patients with microsatellite instability or repair disorder. (MSI / dMMR) stage III colon cancer.1
The study, published in the Journal of Clinical Oncology, also showed that patients with colon cancer and MSI had better outcomes in the N1 group compared with those with persistent microsatellite infection (MSS); however, the two groups saw similar survival in the N2 group. With these conclusions, the researchers suggested that N level should be a stratification parameter in future trials dedicated to the MSI / dMMR population.
“Given that the current work is the largest ever published on preventative CE for patients with MSI stage III [colon cancer], he suggests that FP alone should not be recommended as a diagnostic treatment for these patients, ”wrote the authors of the study, led by Romain Cohen, MD, PhD.
Using the ACCENT database, the researchers evaluated the effect of FP with or without oxaliplatin on disease-free survival (DFS) and total survival (OS) among patients with MSI stage III colon cancer. In addition, the prognostic value of MSI was assessed for FP plus oxaliplatin therapy with serial Cox models modified for demographic and clinopathological factors.
Specifically, for statistical analysis, T level and N level were combined in a complete TN variable (T1–3 and N1: low risk; T4 and / or N2: high risk).
Of the 12 randomized clinical trials identified for the study, MSI status was available among a total of 5457 patients (609 MSI, 11.2%; 4848 MSS, 88.8%). Among patients with MSI colon cancer from 2 randomized clinical trials testing FP with or without oxaliplatin, it was added that oxaliplatin was injected to significantly improve OS (n = 185; modified HR [aHR], 0.52; 95% CI, 0.28–0.93).
“These results differ from the negative results of the FoxTrot test, which showed a very low rate of pathology responses (73.6% no withdrawal) and no survival benefit from neoadjuvant FOLFOX in the 106 MSI / dMMR patients treated in the trial. that, ”noted the authors.2
Furthermore, of 4250 patients treated with FP in addition to oxaliplatin, MSI status (n = 461) was found to be associated with superior OS in the N1 group compared with patients who were assessed as MSS (n = 3789; aHR, 0.66; 95% CI, 0.46–0.95); however, a similar survival was reported in the N2 population (aHR, 1.13; 95% CI, 0.86–1.48; P. interaction = .029). The main predictors of independent prediction in MSI patients treated with FP plus oxaliplatin were T level (aHR, 2.09; 95% CI, 1.29–3.38) and N level (aHR, 3.57; 95% CI, 2.32-5.48). Three-year DFS level estimates of 65.0% (95% CI, 6.0% -70.0%) for patients with N2, MSI / dMMR tumors and 60.4% (95% CI, 52.9% -68.9%) for patients with T4, MSI / dMMR was reported.
“By a third of high risk T4 and / or N2 stage III MSI / dMMR [colon tumors] patients suffering from disease or death within 2 years after therapeutic tumor resection, therapeutic modalities should be sought for this patient population, ”the authors explained.
In particular, 2 stage 3 randomized trials have already been launched for patients with MSI / dMMR stage III colon cancer. These include the ATOMIC test (NCT02912559), which evaluates FOLFOX with or without atezolizumab (Tecentriq); and a POLEM test (NCT03827044), which assesses 24-week use of FP or 12 weeks of FP in addition to oxaliplatin, with or without avelumab (Bavencio), for patients with MSI / dMMR colon cancer or epsilon polymerase- mutated.
References:
1. Cohen R, Taieb J, Fiskum J, et al. Microsatellite instability in patients with stage III colon cancer receiving fluoropyrimidine with or without oxaliplatin: an ACCENT aggregated study of 12 adjuvant trials. J Clin Oncol. Published online December 23, 2020. doi: 10.1200 / JCO.20.01600
2. Morton D. FOxTROT: A randomized controlled trial in 1053 patients evaluating neoadjuvant chemotherapy (NAC) for colon cancer. On behalf of the FOxTROT Collaborative. Ann Oncol. 2019:30 (Suppl 5): v198-v252. doi: 10.1093 / annonc / mdz246