Abstract
Nivolumab is safe and achieves durable responses in metastatic dMMR/MSI-H colorectal cancer.
Major finding: Nivolumab is safe and achieves durable responses in metastatic dMMR/MSI-H colorectal cancer.
Approach: The open-label phase II CheckMate 142 trial evaluated the safety and activity of nivolumab monotherapy.
Impact: Nivolumab warrants further investigation alone and in combination therapies to treat dMMR/MSI-H tumors.
Patients with metastatic colorectal cancer that is DNA mismatch repair–deficient (dMMR) and microsatellite instability-high (MSI-H) have a poor prognosis and a high mutational burden, tumor neoantigen load, and infiltration of immune cells. These findings suggest the potential for the use of immune checkpoint inhibitors to treat patients with dMMR/MSI-H colorectal cancer, and early clinical trials have demonstrated encouraging results for immune checkpoint blockade. Overman and colleagues evaluated the activity and safety of the PD-1 inhibitor nivolumab in the CheckMate 142 trial, a multicenter, open-label, phase II study. A total of 74 heavily pretreated patients with dMMR/MSI-H metastatic colorectal cancer were treated with nivolumab. The primary endpoint was objective response, and exploratory endpoints included safety and tolerability of nivolumab, progression-free survival, and biomarker analysis. Objective responses were achieved in 23 patients (31.1%) who all had partial responses, and disease control for at least 12 weeks occurred in 51 patients (69%). Responses were durable; median duration of response had not yet been reached and the median progression-free survival was 14.3 months. Tumor expression of PD-L1 was not predictive of response. Further, the presence of BRAF or KRAS mutations or a history of Lynch syndrome were not associated with response. Nivolumab was well tolerated, although drug-related grade 3 or 4 events occurred in 15 patients (20%), most commonly increased concentrations of lipase (8%) or amylase (3%). Taken together, the results of this phase II trial suggest that nivolumab monotherapy is safe and has durable antitumor activity in patients with dMMR/MSI-H colorectal cancer, supporting further investigation of nivolumab alone or in combination with other therapies.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.
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