Stereotactic body radiotherapy (SBRT) in combination with pembrolizumab and trametinib improved survival when compared with SBRT plus gemcitabine in patients with locally recurrent, resected pancreatic cancer, according to results of a study published in The Lancet Oncology.
The phase 2 trial (ClinicalTrials.gov Identifier: NCT02704156) enrolled adult patients with pancreatic cancer who had local recurrence after surgery followed by chemotherapy.
In all, 170 patients were randomly assigned to receive SBRT plus pembrolizumab and trametinib (n=85) or SBRT plus gemcitabine (n=85). Treatment continued until disease progression, unacceptable toxicity, death, or withdrawal of consent.
Overall survival (OS) was the primary endpoint. The median follow-up was 23.3 months.
The median OS was 24.9 months in the pembrolizumab-trametinib arm and 22.4 months in the gemcitabine arm (hazard ratio [HR], 0.60; 95% CI, 0.44-0.82; P =.0012). The OS rate at 2 years was 56.5% and 37.6%, respectively.
The median progression-free survival (PFS) was 18.3 months in the pembrolizumab- trametinib arm and 15.6 months in the gemcitabine arm (HR, 0.52; 95% CI, 0.38-0.72; P =.0006). The PFS at 2 years was 15.3% and 4.7%, respectively.
The incidence of grade 3-4 adverse events (AEs) was higher in the pembrolizumab- trametinib arm (31%) than in the gemcitabine arm (20%).
Grade 3-4 AEs that were more frequent in the pembrolizumab-trametinib arm than in the gemcitabine arm were increased alanine aminotransferase or aspartate aminotransferase (12% vs 7%) and increased blood bilirubin (5% vs 0%).
Grade 3-4 AEs that were more frequent in the gemcitabine arm than in the pembrolizumab-trametinib arm were neutropenia (11% vs 1%) and thrombocytopenia (5% vs 1%).
Serious AEs occurred in 22% of patients in the pembrolizumab-trametinib arm and in 14% of patients in the gemcitabine arm. There were no treatment-related deaths in either arm.
“The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery,” the study authors wrote. “Phase 3 trials are needed to confirm our findings.”
Zhu X, Cao Y, Liu W, et al. Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2021;22(8):1093-1102. doi:10.1016/S1470-2045(21)00286-2