Although the primary endpoint of this phase 2 study was not met, the addition of nivolumab to the standard first-line treatment for metastatic colorectal cancer showed an increase in the 15-month progression-free survival rate – higher response rates and durable response.
Standard first-line treatments for patients with metastatic colorectal cancer (mCCR) include a fluoropyrimidine plus oxaliplatin and/or irinotecan, and a biologic agent. It is possible that treatment with nivolumab (NIVO) enhances the antitumor activity of first-line treatments in a subset of patients with mCRC.
The CheckMate 9X8 study was presented at ASCO GI 2022 and evaluated the efficacy of adding NIVO to the conventional regimen mFOLFOX6 plus bevacizumab (mFOLFOX6/BEV) in the first-line treatment of patients with mCRC.
Patients with unresectable and previously untreated mCCR were randomized 1:2 to receive mFOLFOX6/BEV every 2 weeks (SOC) or NIVO 240mg + SOC every 2 weeks. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), overall survival (OS), and safety.
In total, 195 patients were randomized, 68 to SOC and 127 to NIVO + SOC. The median follow-up time was 23.2 (0–32.3) months for SOC and 23.7 (0–33.2) months for NIVO + SOC. The mean duration of treatment was 7.7 (0.1–26.7+) months for SOC and 9.9 (0.1–31.8+) months for NIVO + SOC. The median PFS was 11.9 months for both treatment regimen (HR 0.81 [95% CI 0.53–1.23]; P = 0.30) – which did not reach the statistically significant level for the study. PFS rates were 21.5% and 45% in 15-months for SOC and NIVO + SOC respectively.
The addition of NIVO to the SOC regimen increased the ORR from 46% to 60% (OR 1.72 [95% CI 0.96–3.10]). The median DOR was 9.3 (7.5–11.3) months for SOC and 12.9 (9.0–13.1) months for NIVO + SOC. Grade 3 or 4 adverse event rate increased from 48% to 75% with the addition of NIVO to the SOC regimen and the compatible event rate for treatment discontinuation increased from 10% to 25%.
Complementary analyzes evaluating biomarkers, including TMB and baseline CD8 lymphocyte levels, will be presented in future analyses – which may lead to a selection of patients who benefit most from the increase in standard treatment with NIVO.
Although the primary endpoint of the study was not reached, the addition of NIVO to SOC for first-line treatment resulted in an increase in the rate of PFS at 15 months of follow-up, a greater ORR and more durable responses compared to SOC.
1. Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): Phase 2 results from CheckMate 9X8. Disponível em https://meetings.asco.org/abstracts-presentations/204529.