Bristol Myers Squibb's Opdivo (nivolumab) plus Yervoy (ipilimumab) has shown promising results in a late-stage study for metastatic colorectal cancer (CRC). The CheckMate-8HW trial evaluated the combination against Opdivo alone in patients with microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) metastatic CRC. Results presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium indicated a statistically significant and clinically meaningful 38% reduction in the risk of disease progression or death compared to Opdivo monotherapy, with a median follow-up of 47 months.
Efficacy of Opdivo Plus Yervoy
The phase 3 CheckMate-8HW trial demonstrated a significant improvement in progression-free survival (PFS) for patients treated with the Opdivo/Yervoy combination. Median PFS was not reached with Opdivo plus Yervoy versus 39.3 months with Opdivo monotherapy. PFS rates at 12, 24, and 36 months were 76%, 71%, and 68% respectively, for the combination, compared to 63%, 56%, and 51% for Opdivo alone. These results indicate a sustained benefit over time with the dual immunotherapy approach.
Thierry André, MD, head of the Medical Oncology Department at Sorbonne University and Hospital Saint-Antoine, Paris, presented the data and stated, "[Opdivo] plus [Yervoy] demonstrated statistically significant and clinically meaningful improvement in PFS versus [Opdivo] in patients with centrally confirmed [MSI-H or dMMR metastatic CRC] across all lines [of therapy]." He added that these results, combined with previous findings, establish Opdivo plus Yervoy as a new standard of care for patients with MSI-H/dMMR metastatic CRC.
Objective Response and Disease Control
The objective response rate (ORR) was also significantly higher in the Opdivo plus Yervoy arm, with 71% of patients experiencing a complete or partial response compared to 58% in the Opdivo alone arm. Complete responses occurred in 30% of patients in the combination arm and 28% in the monotherapy arm, while partial responses occurred in 40% and 30%, respectively. The median time to response was similar in both arms, at 2.8 months.
Safety and Tolerability
The safety profile of the Opdivo/Yervoy combination was consistent with previously reported data. Any-grade treatment-related side effects occurred in 81% of patients receiving the combination and 71% of patients receiving Opdivo monotherapy. Common side effects included itching, diarrhea, and underactive thyroid. Grade 3 or higher treatment-related side effects were more common in the combination arm, with adrenal insufficiency being the most frequent.
Implications for Treatment of MSI-H/dMMR mCRC
These findings suggest that the combination of Opdivo and Yervoy could offer a more effective treatment option for patients with MSI-H/dMMR metastatic CRC, who typically have a poor prognosis and are less likely to benefit from conventional chemotherapy. The dual immunotherapy approach targets different immune checkpoints, potentially leading to a more robust and durable anti-tumor response.
Dana Walker, vice president at Bristol Myers Squibb, commented on the results, stating, "The benefit of dual inhibition of PD-1 and CTLA-4 has been well established in phase 3 trials of Opdivo plus Yervoy across a broad range of tumor types, including in MSI-H/dMMR metastatic CRC compared to chemotherapy... The results from this analysis of the CheckMate-8HW trial answer affirmatively an important question about whether dual immunotherapy with Opdivo plus Yervoy can also improve outcomes for patients with MSI-H/dMMR metastatic CRC compared with Opdivo alone."
