According to the phase 3 CheckMate 8HW trial, a treatment combining two immunotherapies, nivolumab (anti-PD1) and ipilimumab (anti-CTLA-4), used as first-line treatment, significantly reduces the progression-free survival of patients with metastatic colorectal cancer with MSI-H or dMMR. The results of this international trial conducted by teams from the medical oncology department of Saint-Antoine hospital in Paris (AP-HP) and Sorbonne University, in collaboration with investigators from 23 countries, were published in the New England Journal of Medicine.
“DNA repair defects (such as MSI-H and dMMR) are reported in approximately 4-7% of metastatic colorectal cancer cases”indicate the authors. “Patients with MSI-H or dMMR metastatic colorectal cancer generally have poor outcomes when treated with standard chemotherapy with or without targeted therapy. »
The KEYNOTE-177 study has already shown the benefit of anti-PD1 immunotherapy pembrolizumab as first-line treatment and as monotherapy compared to chemotherapy in terms of progression-free survival in these patients. Pembrolizumab has had marketing authorization in this indication since 2021.
In this open-label phase 3 trial, some 303 patients with unresectable or metastatic colorectal cancer who had not yet received systemic treatment were included between August 2019 and April 2023 and randomized: 202 received dual immunotherapy and 101 chemotherapy with or without targeted therapy (at the discretion of the investigator); 85% of patients in the immunotherapy group and 83% of those in the chemotherapy group had confirmed MSI-H or dMMR status. The median follow-up duration was 31.5 months.
Results comparing double immunotherapy to nivolumab alone expected
Among patients with confirmed MSI-H or dMMR status, progression-free survival at 12 months was 79% with dual immunotherapy and 21% with chemotherapy. At 24 months, progression-free survival was 72% and 14%, respectively. The differences between the two groups were significant.
The benefit of the nivolumab + ipilimumab combination was consistent in all subgroups, particularly in patients with RAS or BRAF mutations and liver, lung or peritoneal metastases at baseline.
Furthermore, the benefit on quality of life was greater with double immunotherapy than with chemotherapy.
Grade 3 or 4 treatment-related adverse events were reported in 23% of patients in the immunotherapy group and in 48% of those in the chemotherapy group.
“The progression-free survival results are consistent with data from the non-randomized CheckMate 142 study, and they support the use of nivolumab + ipilimumab in MSI-H or dMMR metastatic colorectal cancer,” underline the authors.
The CheckMate 8HW trial is still ongoing and has a third treatment arm including patients receiving only nivolumab. New results comparing the nivolumab + ipilimumab combination to nivolumab monotherapy “will be presented by Professor Thierry André at the next ASCO-GI congress, which will be held from January 23 to 25, 2025 in San Francisco”we read in a press release from the AP-HP.
