Nivolumab (NIVO) plus Ipilimumab (IPI) vs Chemotherapy (Chemo) or NIVO Monotherapy for Microsatellite Instability-high/mismatch Repair-deficient (MSI-H/dMMR) Metastatic Colorectal Cancer (mCRC): Expanded Analyses from CheckMate 8HW
Dr.Heinz-Josef Lenz
Introduction
Dr. Lenz presented the expanded analysis of phase 3 CheckMate 8HW, demonstrating the long-term efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) compared to chemotherapy (chemo) or NIVO monotherapy in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).
Methods
- Patients with histologically confirmed MSI-H/dMMR mCRC were randomized globally to receive either NIVO+IPI, NIVO monotherapy, or chemotherapy.
- The dual primary endpoints included progression-free survival of NIVO + IPI versus chemotherapy and progression-free survival of NIVO + IPI versus NIVO, both evaluated in centrally confirmed dMMR populations.
- The follow-up data was up to August 28, 2024 (median: 47 months).
Results
- NIVO+ IPI continued to show sustained improvements in PFS compared to chemotherapy (54.1 vs. 5.9 mo; HR: 0.21). 16% of NIVO+IPI patients needed subsequent therapy compared to 73% of chemotherapy patients.
- A 43% reduction in mortality or progression was observed with NIVO + IPI versus nivolumab (HR: 0.62) in PFS2, with a 3-year PFS rate of 83% and 66%, respectively.
- Higher RR(71% vs. 58%) were achieved with NIVO+ IPI.
- Grade 3-4 treatment-related adverse events were more frequent in NIVO+IPI (22%) compared to NIVO (14%), with most occurring in the first 6 months. No new safety signals were observed.
Conclusion
The expanded analyses from the CheckMate 8HW study reinforced that NIVO+ IPI offers sustained and significant clinical advantages for patients with centrally confirmed MSI-H/dMMR metastatic colorectal cancer. The combination has shown superior outcomes compared to chemotherapy and nivolumab.
Long-term Safety and Efficacy of Sotorasib plus Panitumumab and FOLFIRI for Previously Treated KRAS G12C-mutated Metastatic Colorectal Cancer (mCRC): CodeBreaK 101 (Phase 1b)
Dr. John H. Strickler
Introduction
The speaker, Dr. John, reported the long-term safety and efficacy results from CodeBreaK 101 investigating sotorasib (KRASG12C inhibitor) plus panitumumab (monoclonal anti-EGFR antibody) and FOLFIRI in previously treated KRAS G12C-mutated metastatic colorectal cancer. The median followed up period was 32 months.
Methods
- This international, multicenter, open-label study involved 46 patients: 6 patients in the dose-escalation phase and 40 patients in a dose-expansion cohort.
- The patients had KRAS G12C-mutated metastatic colorectal cancer and had received at least one prior systemic treatment.
- Sotorasib (960 mg orally daily) was administered along with standard doses of panitumumab (6 mg/kg intravenous every 2 weeks) and FOLFIRI (administered intravenous every 2 weeks).
- The primary endpoint was safety and tolerability, while the secondary endpoints included RR, DoR, PFS, & OS.
Results
- An ORR of 57.5% was reported, with all responses being partial. The mDoR was 6.6 mo.
- mOS was 15.6 mo, while mPFS was 8.2 mo.
- Patients with only one prior line of therapy had a higher response rate (69%) and longer mOS of 22 mo.
- The efficacy was maintained even in patients previously treated with irinotecan. The safety profile was favourable, with most treatment-related adverse events being low-grade and manageable (Neutropenia, diarrhoea). No new toxicities were observed.
Conclusion
The combination of sotorasib, panitumumab, and FOLFIRI showed sustained efficacy and manageable safety in pretreated KRAS G12C-mutated metastatic colorectal cancer.
ASCO 2025, May 30 – June 3, Chicago
