What is the response rate for single-agent immunotherapy in metastatic colorectal cancer (mCRC)?

From the Guidelines

Response Rate for Single-Agent Immunotherapy in mCRC

The response rate for single-agent immunotherapy in metastatic colorectal cancer (mCRC) is generally low, ranging from 0-5% for checkpoint inhibitors such as pembrolizumab and nivolumab, in patients with microsatellite stable (MSS) tumors 1. However, in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, the response rate can be higher, ranging from 20-40% for single agent pembrolizumab or nivolumab 1.

Key Findings

• The immune-related objective response rates were 40% (95% CI, 12–74) in the dMMR CRC group, 0% (95% CI, 0–20) in the pMMR CRC group, and 71% (95% CI, 29–96) in the dMMR noncolorectal group 1.
• Another phase II study, KEYNOTE-164, reported an ORR of 33% for both cohorts of patients with MSI-H/dMMR mCRC 1.
• The CheckMate-142 trial reported an ORR of 31.1% (95% CI, 20.8–42.9) for patients with dMMR CRC treated with nivolumab, and 55% (95% CI, 45.2–63.8) for those treated with nivolumab plus ipilimumab 1.

Treatment Considerations

• The typical dose for pembrolizumab is 200mg every 3 weeks, and for nivolumab, it is 240mg every 2 weeks or 480mg every 4 weeks.
• Treatment is usually continued until disease progression or unacceptable toxicity.
• Checkpoint inhibitor immunotherapy is recommended as a subsequent-line treatment option in patients with metastatic MMR-deficient CRC who have not previously received a checkpoint inhibitor 1.

From the Research

Response Rate for Single-Agent Immunotherapy in mCRC

• The response rate for single-agent immunotherapy in metastatic colorectal cancer (mCRC) is limited to patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors 2.
• A systematic review of clinical outcomes found that single PD-1/PD-L1 checkpoint blockade provides durable clinical response in mCRC patients with MSI-H, with response rates ranging from 20-30% 2.
• The KEYNOTE-028 uncontrolled phase II trial demonstrated an impressive antitumor activity of pembrolizumab in patients with treatment-refractory Lynch-associated tumors, including colorectal cancer, with a response rate of 50% 3.
• However, for patients with microsatellite stable (MSS) mCRC, the response rate to single-agent immunotherapy is low, and combination therapies are being explored to overcome resistance 4, 5.

Predictive Biomarkers and Combination Therapies

• Predictive biomarkers, such as tumor mutation burden (TMB) and microsatellite instability (MSI) status, are crucial in identifying patients who may benefit from immunotherapy 2, 4.
• Combination therapies, such as nivolumab plus ipilimumab, have shown promising results in patients with MSI-H mCRC, with response rates ranging from 30-50% 6, 3.
• Emerging evidence suggests that combination of immune modulators, such as regorafenib, may improve the responsiveness of MSS mCRC to checkpoint blockade 5.

Ongoing Research and Future Directions

• Further research is needed to identify predictive biomarkers and develop effective immunotherapy strategies for patients with MSS mCRC 4, 5.
• Investigative studies are underway to overcome tumor resistance in current immunotherapy approaches, including combination therapies and novel therapeutic strategies 4, 5.