In a French phase II study (IMHOTEP) reported in the Journal of Clinical Oncology, de la Fouchardière et al found that perioperative pembrolizumab was active in previously untreated resectable localized colorectal cancer with mismatch repair deficiency (dMMR)/microsatellite instability (MSI).
Study Details
In the multicenter trial, 72 evaluable patients enrolled between November 2021 and February 2023 received one or two cycles of pembrolizumab at 400 mg every 6 weeks before surgery and pembrolizumab at 400 mg every 6 weeks thereafter for a 1-year total duration of treatment. The primary endpoint was pathologic complete response (pCR) rate (ypT0N0). Secondary objectives included event-free survival and overall survival.
Key Findings
In total, pCR was achieved by 38 patients (52.7%, 95% confidence interval [CI] = 41.4%–63.9%). Post hoc analysis showed that the pCR rate increased from 46% (23 of 50 patients) after one cycle of neoadjuvant pembrolizumab to 68.2% (15 of 22 patients) after two cycles (P = .0125).
At a median follow-up of 24.5 months (95% CI = 23.3–25.6 months), cancer-related events occurred in five patients (6.9%), including progression in one, recurrence in three, and death in one. Overall survival at 24 months was 98% (95% CI = 88%–100%).
Grade ≥ 3 treatment-related adverse events occurred in 14 patients (15.7%), including 5 before surgery and 7 after surgery; the most common was hepatitis (n = 2, 3%). One treatment-related death was reported, due to myasthenia.
The investigators concluded: “The IMHOTEP trial showed promising results, with pCR achieved after one or two cycles of neoadjuvant pembrolizumab in 53% of patients with dMMR/MSI [colorectal cancer]. To our knowledge, this prospective study is the first to demonstrate the feasibility and the safety of perioperative pembrolizumab.”
Christelle de la Fouchardière, MD, of the Medical Oncology Department, Paoli-Calmettes Institute, Aix-Marseille University, Marseille, France, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the French Ministry of Health, French National Cancer Institute, MSD France, and others. For full disclosures of the study authors, visit ascopubs.org.
