Benefit of first-line nivolumab/ipilimumab in MSI-H/dMMR metastatic CRC

First-line treatment of patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC) using nivolumab/ipilimumab combination therapy demonstrated superior progression-free survival (PFS) compared with chemotherapy. In addition, PFS with subsequent therapy favoured nivolumab/ipilimumab in the ongoing phase 3 CheckMate 8HW trial.

Immunotherapy is recommended in guidelines for the treatment of patients with MSI-H/dMMR metastatic CRC not previously treated with immunotherapy. Favourable efficacy outcomes have been observed with the nivolumab/ipilimumab combination therapy compared with single-agent immunotherapy in MSI-H/dMMR mCRC [1].

The ongoing, randomised, phase 3 CheckMate 8HW trial (NCT04008030) compared the efficacy and safety of first-line nivolumab monotherapy versus nivolumab/ipilimumab combination therapy versus chemotherapy in patients with unresectable or metastatic MSI-H/dMMR CRC. Prof. Heinz-Josef Lenz (University of Southern California Norris Comprehensive Cancer Center, CA, USA) presented the results of arm 2 and arm 3 after a median follow-up of 31 months [2].

A total of 303 participants were 2:1 randomised to receive nivolumab/ipilimumab for 4 cycles, followed by nivolumab monotherapy, or to chemotherapy (investigator’s choice). The median PFS was significantly longer with nivolumab/ipilimumab compared with chemotherapy (not reached vs 5.9 months; HR 0.21; 97.91% CI 0.13–0.35; P<0.0001; see Figure). The 24-month PFS rates were 72% and 14%, respectively. Nivolumab/ipilimumab favoured median PFS in all subgroups.

Figure: Progression-free survival rates in CheckMate 8HW [2]



CI, confidence interval; HR, hazard ratio; IPI, ipilimumab; NIVO, nivolumab; PFS, progression-free survival.

After progression on first-line therapy, 171 participants in the nivolumab/ipilimumab arm and 84 participants in the chemotherapy arm received subsequent therapy (in the chemotherapy arm, 67% of participants received subsequent immunotherapy). PFS on second-line treatment was also superior in participants treated with nivolumab/ipilimumab as first-line treatment compared with those who received first-line chemotherapy. The 24-month PFS2 rates were 83% and 52%, respectively.

Grade 3/4 treatment-related adverse events were more frequently observed in participants treated with (first-line) chemotherapy (48% vs 23%), despite a longer treatment duration in the nivolumab/ipilimumab arm.

“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 CRC,” concluded Prof. Lenz.

1. Andre T, et al. Ann Oncol. 2022;33:1052-1060.
2. Lenz H-J, et al. Nivolumab plus ipilimumab vs chemotherapy as first-line treatment for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: expanded efficacy analysis of CheckMate 8HW. Abstract LBA3503, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

Posted on 18 July 202419 July 2024