S775
Clinical - Lung
ESTRO 2026
Purpose/Objective: Immunotherapy (IO) has significantly improved outcomes in metastatic non–small cell lung cancer (mNSCLC). However, due to heterogeneous immune responses, not all patients benefit. Radiotherapy (RT) may enhance systemic immune activation when combined with IO, though the optimal radiation dose and schedule remain unclear. The main objective of this study was to evaluate whether upfront palliative RT before standard chemoimmunotherapy (ChT/IO) improves progression-free survival (PFS) in mNSCLC. Material/Methods: In this prospective, interventional, non-randomized, multicenter phase II trial, 50 consecutive patients with non-oncogene driven, PD-L1 <50% mNSCLC eligible for first-line ChT/IO were enrolled. Limited asymptomatic brain metastases (BM) after ablative treatment were allowed. Palliative RT (20 Gy in 5 fractions) was delivered to the primary and up to five metastatic sites, followed by platinum-based chemotherapy and anti–PD-1 therapy. Combined adverse events were recorded at 2, 4 and 6 weeks after RT. PFS in the experimental group (EG) was compared to a retrospective historical cohort group (RHCG) of patients treated with identical ChT/IO but without RT. The RHCG was selected from 158 cases (2015–2024) using propensity score matching (1:1). Survival was analyzed using the Kaplan–Meier method, with comparisons by log-rank test. Results: Between July 2022 and January 2025, 50 patients were enrolled, of whom 47 were evaluable (Figure 1). All received RT and at least one ChT/IO cycle. The median time from diagnosis to systemic therapy was 41 days (range 16-101) in the EG and 38 days (11-131) in the RHCG. The median time from irradiation to initiation of systemic therapy was 7 days (range 1-55). With a median follow-up of 14.1 months (0.1 – 59.4), 38 events (progression/death) occurred in the EG and 42 in the RHCG. Median PFS was 5.7 months (95% CI 3.5– 8.0) in the EG and 8.1 months (95% CI 6.4–9.9) in the RHCG (p=0.659) (Figure 2). Among PD-L1–positive patients, median PFS was 5.7 vs. 11.9 months (p=0.675), and among PD-L1–negative patients, 5.3 vs. 6.6 months (p=0.809) for the EG and RHCG, respectively. All adverse events were grade 1–2. No clinically significant pneumonitis occurred, but a possible grade 5 liver failure was reported after the first ChT/IO cycle.
Conclusion: Upfront palliative radiotherapy before chemoimmunotherapy did not improve progression- free survival in mNSCLC but was well tolerated. Further prospective trials are needed to determine the optimal integration and sequencing of radiotherapy with systemic therapy. References: 1. Shaverdian N, Lisberg AE, Bornazyan K, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non- small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol. 2017;18(7):895-9032. Theelen WSME, Peulen HMU, Lalezari F, et al. Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer: results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA Oncol. 2019;5(9):1276-1282.3. Brooks ED, Chang JY. Time to abandon single-site irradiation for inducing abscopal effects. Nat Rev Clin Oncol. 2019 Feb;16(2):123-135. Keywords: Immuno-radiotherapy,
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