Neoadjuvant Pembrolizumab Yields High Response Rates Among Patients With Microsatellite Instability High/Deficient Mismatch Repair Colorectal Cancer

For patients with microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors including colorectal cancer, neoadjuvant pembrolizumab is safe and yielded high rates of pathologic, radiographic, and endoscopic response, according to results from a phase 2 trial.

In this open-label, single-center, phase 2 trial, 35 patients with localized unresectable or high-risk resectable MSI-H/dMMT tumors (colorectal cancer, n = 27) were enrolled. Patients received 200 mg pembrolizumab every 3 weeks for 6 months, followed by surgical resection. Following this schedule, pembrolizumab therapy for 1 year with observation was optional for patients with radiographic or clinical benefit. The co-primary end points of the study were safety and pathologic complete response, and secondary end points included response rate, and organ-sparing at 1 year for patients who declined surgery.

At the time of data cutoff, 33 patients were evaluable. The best overall response rate was 82%. The pathological complete response rate of those patients who underwent surgery (n = 17) was 65%. There were 18 total patients who pursued nonoperative management, 10 who received an additional 1 year of pembrolizumab plus surveillance and 8 who received less than 1 year of additional pembrolizumab. Among those patients who opted for nonoperative management, durable response were in the majority. There were 6 patients who experienced progression events, with 4 of them undergoing salvage surgery.

Kaysia Ludford, MD, University of Texas MD Anderson Cancer Center, Houston, TX, and coauthors concluded that preoperative pembrolizumab “resulted in high rates of pathologic, radiographic, and endoscopic response,” adding that this regimen “has implications for organ-sparing strategies” and “definitive nonsurgical management with the use of immunotherapy in MSI-H/dMMR tumors is promising and warrants further exploration.”

Journal of Clinical Oncology associate editor, Eileen M O’Reilly, MD, Memorial Sloan Kettering, New York, NY, also added, “this study adds to the growing body of evidence that endorses the role of anti-programmed death protein-1 therapy in GI cancers with dMMR/MSI-H, where deep and pathologic response are observed in a substantial majority of patients with localized disease.”

Source:

Ludford K, Ho WJ, Thomas JV, et al. Neoadjuvant pembrolizumab in localized microsatellite instability high/deficient mismatch repair solid tumors. J Clin Oncol. Published online January 9, 2023. doi:10.1200/JCO.22.01351