First-line treatment of patients with microsatellite instability-high/mismatch repair deficient (MSI-H/sMMR) metastatic colorectal cancer (mCRC) with ipilimumab nivolumab combination demonstrated a superior progression-free survival (PFS) versus chemotherapy. In addition, PFS of subsequent therapy favored ipilimumab/nivolumab, according to the results of CheckMate 8HW.
Immunotherapy such as nivolumab, and pembrolizumab, is recommended in guidelines for the treatment of MSI-H/dMMR mCRC not previously treated with immunotherapy. Favorable efficacy outcomes have been observed with nivolumab/ipilimumab combination therapy relative to single agent immunotherapy in MSI-H/dMMR mCRC1.
The ongoing, randomized, phase 3 CheckMate 8HW trial (NCT04008030) compares the efficacy and safety of first line nivolumab monotherapy versus nivolumab/ipilimumab combination therapy versus investigator’s choice chemotherapy in patients with unresectable or metastatic MSI-H/dMMR CRC. Prof. Heinz-Josef Lenz, MD, of the University of Southern California Norris Comprehensive Cancer Center, presented the results of arm two and arm three after a median follow up of 31 months2 .
A total of 303 patients were 2:1 randomly assigned to receive nivolumab/ipilimumab for four cycles followed by nivolumab monotherapy or to receive investigator’s choice chemotherapy. Median PFS was significantly longer with nivolumab/ipilimumab versus chemotherapy: not reached and 5.9 months, (HR 0.21; 95% CI .013-0.35; P<0.0001). PFS rate at 24 months was 72% and 14%, respectively. Nivolumab/ipilimumab favored median PFS in all subgroups.
After progression on first line therapy, 171 patients in the nivolumab/ipilimumab arm and 84 patients in the chemotherapy arm received subsequent therapy in the chemotherapy arm 67% of patients received subsequent immunotherapy. PFS on second line treatment was also superior in patients treated with nivolumab/ipilimumab in first line versus patients who had received first line chemotherapy. The 24-months PFS rate was 83% and 52%.
Grade 3/4 treatment related events were more frequently observed in patients treated with first line chemotherapy despite a longer duration of treatment in the nivolumab/ipilimumab arm: 48% versus 23%.
“These results provide further evidence to support nivolumab/ipilimumab as a standard-of-care, first-line treatment option for patients with MSI-H/dMMR metastatic colorectal cancer,” concluded Prof. Lenz.
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