News
Article
Nivolumab Plus Ipilimumab Receives FDA Approval for MSI-H/dMMR mCRC
Author(s):
Key Takeaways
- The FDA approved nivolumab and ipilimumab for MSI-H/dMMR colorectal cancer in patients aged 12 and older, based on CHECKMATE-8HW trial data.
- The trial showed significantly improved progression-free survival with nivolumab plus ipilimumab compared to chemotherapy.
The approval was based on efficacy and safety data from a randomized, 3-arm, open-label phase 3 CHECKMATE-8HW trial.
The FDA has approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for the treatment of unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) in adult and pediatric patients aged 12 years and older.1
Image credit: Araki Illustrations | stock.adobe.com
According to a release from the FDA, the approval was based off efficacy and safety data from a randomized, 3-arm, open-label phase 3 CHECKMATE-8HW trial (NCT04008030) that assessed the use of nivolumab in immunotherapy-naïve individuals with unresectable or metastatic CRC with known MSI-H or dMMR status. 1 The study aimed to compare how well nivolumab works, either when given with ipilimumab or by itself, measured by progression-free survival (PFS), objective response rate (ORR), and overall survival (OS).2 Data from the study demonstrated significantly improved PFS with the combination versus chemotherapy.1
Nearly 1147 individuals were included in the study and were randomly assigned to receive 240 mg of nivolumab every 3 weeks and a 1 mg/kg dose of ipilimumab every 3 weeks for a maximum of 4 doses, then 480 mg of nivolumab every 4 weeks; or 240 mg of nivolumab every 2 weeks for 6 doses, then 480 mg of nivolumab every 4 weeks; or investigator's choice chemotherapy. Additionally, the study specifically compared nivolumab plus ipilimumab against chemotherapy in the first-line setting and nivolumab plus ipilimumab against just nivolumab in all patients who had received prior treatment in all lines.1
A total of 255 individuals with centrally confirmed MSI-H/dMMR status of 303 individuals based on local testing were included in the first-line setting. The results demonstrated that the median PFS was not reached (NR) (95% CI: 38.4, not estimable) with nivolumab plus ipilimumab and was 5.8 months (95% CI: 4.4, 7.8) in the chemotherapy arm (Hazard ratio 0.21 [95% CI: 0.14, 0.32], P <.0001). However, the FDA noted that the study did not yet gather enough data to compare ORR or OS between the treatment groups.1
In all lines, a total of 582 individuals were included with centrally confirmed MSI-H/dMMR status of 707 individuals based on local testing. Similar to the first line, the median PFS was NR (95% CI: 53.8, NE) in the nivolumab plus ipilimumab, and was 39.3 months in the nivolumab arm (Hazard ratio 0.62 [95% CI: 0.48, 0.81], P-value .0003). Further results demonstrated that the ORR was 71% (95% CI: 65, 76) in the nivolumab + ipilimumab arm and 58% (95% CI: 52, 63) in the nivolumab arm (p-value .0011). However, not enough data was drawn at the time of initial results to compare OS between treatment groups.1
Additionally, the most common adverse reactions reported in at least 20% of individuals treated with nivolumab plus ipilimumab included fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. In individuals treated with nivolumab alone, around 20% of individuals reported fatigue, diarrhea, abdominal pain, pruritis, and musculoskeletal pain. The study authors noted that the safety profile was tolerable and consistent with previous data.1
In addition to the approval, the FDA converted the accelerated approval to regular approval for nivolumab as a single agent for adult and pediatric patients 12 years of age and older with MSI-H or dMMR metastatic CRC that has progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan.1
