In a Chinese phase II trial reported in The Lancet Oncology, Zhu et al found that stereotactic body radiotherapy (SBRT) plus pembrolizumab and trametinib produced a modest—but statistically significant—overall survival benefit vs SBRT plus gemcitabine in patients with locally recurrent resected pancreatic cancer.
Study Details
The multicenter, open-label trial included 170 patients with local disease recurrence after surgery followed by chemotherapy with modified FOLFIRINOX (fluorouracil [5-FU], leucovorin, irinotecan, and oxaliplatin) or 5-FU. Patients were randomly assigned between October 2016 and October 2017 to receive SBRT plus pembrolizumab and trametinib (n = 85) or SBRT plus gemcitabine (n = 85). SBRT was given at 35 to 40 Gy in 5 fractions. Starting 1 week after SBRT, patients received pembrolizumab at 200 mg every 3 weeks and trametinib at 2 mg once daily until disease progression or unacceptable toxicity, or gemcitabine at 1,000 mg/m2 on days 1 and 8 in 21-day cycles for 8 cycles.
The primary endpoint was overall survival in the intention-to-treat population.
KEY POINTS
- SBRT plus pembrolizumab/trametinib significantly prolonged overall survival vs SBRT plus gemcitabine.
- Median overall survival was 24.9 vs 22.4 months, with 2-year rates of 56.5% vs 37.6%.
Overall Survival
As of the clinical cutoff date (November 2020), median follow-up was 23.3 months (interquartile range = 20.5–27.4 months). Median overall survival was 24.9 months (95% CI = 23.3–26.5 months) in the pembrolizumab/trametinib group vs 22.4 months (95% CI = 21.2–23.6 months) in the gemcitabine group (hazard ratio [HR] = 0.60, 95% CI = 0.44–0.82, P = .0012). Rates at 2 years were 56.5% vs 37.6%.
Median progression-free survival was 18.3 months vs 15.6 months (HR = 0.52, 95% CI = 0.38–0.72, P = .0006), with 1-year rates of 90.6% vs 87.1%.
Adverse Events
Grade 3 to 4 adverse events occurred in 31% of patients in the pembrolizumab/trametinib group vs 20% of the gemcitabine group, with the most common being increased alanine aminotransferase/aspartate aminotransferase (12% vs 7%), increased blood bilirubin (5% vs 0%), neutropenia (1% vs 11%), and thrombocytopenia (1% vs 5%). Any-grade hematologic toxicity occurred in 18% vs 32% of patients. Serious adverse events occurred in 22% vs 14% of patients; adverse events led to treatment discontinuation in 2% vs 1%. No treatment-related deaths were reported.
The investigators concluded, “The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery. Phase III trials are needed to confirm our findings.”
Huojun Zhang, MD, of the Department of Radiation Oncology, and Gang Jin, MD, of the Department of Hepatobiliary and Pancreatic Surgery, Changhai Hospital affiliated to Naval Medical University, Shanghai, are the corresponding authors for The Lancet Oncology article.
Disclosure: The study was funded by Shanghai Shenkang Center and Changhai Hospital. For full disclosures of the study authors, visit thelancet.com.
