Safety and Efficacy of PRaG Therapy in Elderly Cancer Patients

Abstract Introduction PD-1/PD-L1 inhibitors lack evidence-based support in patients aged ≥75 years due to their frequent exclusion from clinical trials. This study aimed to evaluate the safety and efficacy of PRaG therapy—combining PD-1/PD-L1 inhibitors with radiotherapy—specifically in this elderly demographic. Methods Data were collected from patients aged ≥75 years who received PRaG therapy at our center between January 1, 2019, and December 31, 2024. Eligible patients were required to have at least one post-baseline efficacy evaluation. Tumor response was evaluated according to RECIST v1.1, and adverse events were graded using CTCAE v5.0. Results A total of 36 elderly patients aged ≥75 years were included, with a median age of 77 years (range: 75-93). The objective response rate (ORR) was 23.5%, and the disease control rate (DCR) was 70.6%. After a median follow-up of 46.3 months, the median progression-free survival (mPFS) was 7.0 months (95% CI: 2.4-11.6 months) and the median overall survival (mOS) was 11.1 months (95% CI: 5.3-16.9 months). The Geriatric Nutritional Risk Index (GNRI) was associated with the efficacy of PRaG therapy, as well as PFS and OS. Any-grade treatment-related adverse events (TRAEs) occurred in 34 patients (94.4%), with 3 patients (8.3%) experiencing ≥Grade 3 TRAEs. No Grade 5 TRAEs were observed. Conclusion The PRaG regimen appears feasible and tolerable in selected elderly patients with advanced cancer. Given the retrospective nature of this small cohort, an ongoing prospective trial (NCT06112041) will further validate these findings. Combining PRaG with robust nutritional support represents a rational hypothesis for future investigation.