Dissociated response to PD-1 inhibitors combined with radiotherapy in patients with advanced metastatic solid tumors: a single-center experience

BACKGROUND: Anti-programmed death 1/anti-programmed death ligand 1 (PD-1/PD-L1) combined with radiotherapy (RT) has a synergistic effect on systemic tumor control. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with immune checkpoint inhibitor (ICI) monotherapy or combination therapy. The objective of this study was to assess the frequency and clinical benefit of DR in patients with advanced metastatic solid tumors receiving PD-1 inhibitors in combination with RT. METHODS: We conducted a single-center retrospective analysis of patients with advanced metastatic solid tumors receiving PD-1 inhibitor combined with RT at the Department of Radiotherapy & Oncology, The Second People’s Hospital Affiliated with Soochow University. Treatment response was assessed for each measurable lesion according to the Response Evaluation Criteria in Solid Tumours ( RECIST) v 1.1 guidelines. Patterns of response are divided into four groups: (1) DR, (2) uniform response, (3) uniform progression, and (4) only stable lesions. The overall survival (OS) of different groups was compared using Kaplan–Meier methods and log-rank tests. RESULTS: Between March 2019 and July 2022, 93 patients were included. The median follow-up was 10.5 months (95% CI 8.8–12.1). The most common tumor types were lung cancer (19.8%), colorectal adenocarcinoma (17.2%), and esophageal cancer (10.8%). DR was observed in 22 (23.7%) patients. The uniform progression and DR are two different patterns of progression. After confirming progression, the overall survival of patients with DR was significantly longer than that of patients with uniform progression (9.9 months (95%CI 5.7-14.1) vs. 4.2 months (95%CI 1.9-6.5), P = 0.028). Compared with DR patients who did not continue PD-1 inhibitor combined with RT or PD-1 inhibitor monotherapy (n = 12), DR patients who continued treatment (n = 10) had significantly longer OS (15.7 (95%CI 3.5-27.9) vs 8.2 (95%CI 5.6-10.8) months, P = 0.035). CONCLUSIONS: DR is not uncommon (23.7%) in patients with advanced metastatic solid tumors treated with PD-1 inhibitors combined with RT and shows a relatively favorable prognosis. Some patients with DR may benefit from continued PD-1 inhibitor therapy in combination with RT or PD-1 inhibitor monotherapy and may have longer OS.