KEY TAKEAWAYS
- The CheckMate 8HW Phase 3 trial aims to investigate the PFS of NIVO + IPI versus chemo as a 1L treatment for MSI-H/dMMR mCRC.
- The primary endpoint was to determine PFS.
- Researchers noticed PFS and a safety profile with NIVO + IPI compared to chemo, as a standard-of-care option for MSI-H/dMMR mCRC pts.
Patients (pts) with microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) metastatic colorectal cancer (mCRC) face poor outcomes with standard chemotherapy (chemo) and targeted therapies. Nivolumab plus ipilimumab (NIVO + IPI) has gained approval for previously treated pts based on positive outcomes in the phase 2 CheckMate 142 study. An ongoing phase 3 trial, CheckMate 8HW (NCT04008030), compared NIVO + IPI with NIVO or chemo as first-line treatment for MSI-H/dMMR mCRC. This study presented progression-free survival (PFS) data, assessed by blinded independent central review (BICR).
Thierry André and his team aimed to assess the efficacy and safety of NIVO + IPI compared to NIVO or chemo in previously untreated MSI-H/dMMR mCRC pts.
They performed an inclusive analysis enrolling pts ≥ 18 years with recurrent or mCRC deemed unsuitable for surgery and confirmed as MSI-H/dMMR through local testing. Participants, spanning various lines of therapy, underwent randomization in a 2:2:1 ratio to receive NIVO (240 mg) + IPI (1 mg/kg) Q3W (4 doses, then NIVO 480 mg Q4W), NIVO (240 mg) Q2W (6 doses, then NIVO 480 mg Q4W), or chemo ± targeted therapies.
Treatment duration extended until disease progression or unacceptable toxicity for all arms, with a maximum limit of 2 years (NIVO ± IPI arms). Optional crossover to NIVO + IPI was allowed for pts with centrally confirmed MSI-H/dMMR mCRC and documented progression by blinded independent central review (BICR) during chemo. Dual primary endpoints PFS by BICR per RECIST v1.1 for NIVO + IPI vs chemo (1L) and NIVO + IPI vs NIVO (all lines) in pts with centrally confirmed MSI-H/dMMR mCRC.
About 303 pts were enrolled in the first-line setting, with NIVO + IPI (n = 202) or chemo (n = 101); of these pts, 171 pts in the NIVO + IPI arm, and 84 in the chemo arm had centrally confirmed MSI-H/dMMR status through either immunohistochemistry or polymerase chain reaction-based tests.
After a median follow-up of 24.3 months, NIVO + IPI exhibited a clinically meaningful and statistically significant enhancement in PFS compared to chemo. The data revealed a substantial 79% reduction in the risk of disease progression or death with a hazard ratio (HR) of 0.21 (95% CI 0.14–0.32; P<0.0001) in favor of NIVO + IPI. Notably, no new safety signals were identified during the course of the study.
The study concluded that NIVO + IPI outperformed chemo in 1L treatment for MSI-H/dMMR mCRC, exhibiting superior PFS and a favorable safety profile. The study supports NIVO + IPI as a recommended standard-of-care option.
The study is sponsored by Bristol-Myers Squibb
Source: https://meetings.asco.org/abstracts-presentations/230735
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04008030
Andre T, Elez E, Cutsem E V, et al. (2023). “Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study.” Presented at ASCO (Abstract LBA768).
