3771 - The Efficacy and Safety Profile of PRaG "Therapy" in Geriatric Patients with Advanced Refractory Solid Malignant Tumors

X. Zhao, P. Xing, Y. Kong, M. Xu, J. J. Zhang, M. Yang, and L. Zhang; Center for Cancer Diagnosis and Treatment, The Second Af?liated Hospital of Soochow University, Suzhou, China

Purpose/Objective(s): Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical benefits for individuals suffering from malignant neoplasms and have been approved for use in a wide range of tumor types. Nevertheless, there exists a paucity of data regarding the effectiveness and safety of immunotherapy in elderly patients due to their frequent exclusion from previous clinical trials investigating the efficacy of immune checkpoint inhibitors (ICIs). The PRaG study, a prospective clinical trial executed by our research collective, focuses on individuals harboring advanced refractory neoplasms. The objective of this investigation was to conduct a retrospective analysis concerning the safety and efficacy of PRaG therapy (a combination of PD-1/PD-L1 inhibitors, Radiotherapy, and GM-CSF, with or without IL-2) in elderly patients aged 75 years or older. Materials/

Methods: Elderly patients aged =75 years in the PRaG study were selected, and the treatment protocol was delineated as follows: identification of appropriate lesions for radiotherapy administration (5 or 8Gy×2-3 fractions), subcutaneous administration of GM-CSF (200 µg/day, d1-14) or a sequential regimen of GM-CSF (200 µg/day, d1-7) followed by IL-2 (2 million IU/day, d8-14), commencing subsequent to the conclusion of radiotherapy. Furthermore, PD-1/PD-L1 inhibitors were administered one week subsequent to the completion of radiotherapy. A single treatment cycle spanned 21 days, subsequent cycles could involve radiotherapy targeting a distinct lesion, with a minimum of =2 cycles of combination therapy administered until either no suitable lesions for irradiation remained or the maximum tolerated dose for normal tissue was achieved. Imaging was performed every six weeks, and efficacy was assessed using RECIST 1.1 criteria, and adverse events were evaluated using CTCAE 5.0.
Results: As of December 31, 2023, a total of 15 patients were enrolled in the study. There were 9 males and 6 females, aged 75-85 years, with a median age of 76 years. Among the participants, 46.7% had previously undergone treatment with three or more lines of therapy. 13 patients underwent at least one imaging evaluation. Objective response rate (ORR) was 30.8% and disease control rate (DCR) was 76.9%. The median progression-free survival (mPFS) was 7.6 months (95% CI, 1.7-13.5 months), and the median overall survival (mOS) was 11.3 months 95% CI (8.3-14.3 months). Thirteen of 15 patients (86.7%) experienced treatment-related adverse events (TRAEs) of any grade, and one (7.7%) discontinued treatment after developing grade 2 immune myocarditis.
Conclusion: PRaG therapy exhibits favorable tolerability in elderly patients with advanced metastatic solid tumors and holds the potential to offer significant benefits to this patient population. The number of cases included in this study is small, and a prospective study is ongoing (NCT06112041).