Radiotherapy for oligoprogressive disease in non-small cell lung cancer treated with pembrolizumab in first-line setting: a retrospective study

Background: Oligoprogression (OP) is common in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs). This study aims to assess the benefit and the safety profile of ablative radiotherapy (RT) for OP in mNSCLC treated with pembrolizumab in first-line setting. Methods: We retrospectively analyzed records of all consecutive mNSCLC patients who underwent treatment with pembrolizumab (+/- chemotherapy) in first-line setting and developed an OP treated with ablative RT while continuing pembrolizumab, in a French Hospital from 2019 to 2022. Primary endpoint was time to next systemic treatment (TTNT). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profile. Furthermore, we investigated features associated with clinical outcomes. Results: Thirty-six patients were included and 47 OPs were reported (27 patients experienced one OP, 7 two OP, and 2 three OP). The median TTNT (mTTNT) after the first OP was 19.6 months [95% confidence interval (CI): 12.4-not reached (NR)]. The median PFS (mPFS) after the first OP was 12 months (95% CI: 6.1-NR) and 10.4 months (95% CI: 3.9-NR) after the second or third OP. The median OS (mOS) from the first OP and from pembrolizumab initiation were NR. In multivariable analysis, the presence of adrenal gland was associated with shorter TTNT and OS, while OP involving bone metastasis was associated with shorter PFS. The ORR of the lesions treated with RT was 70.2%. No RT-induced severe adverse event was reported. Three patients experienced severe pembrolizumab-induced adverse events. Conclusions: In this study, RT alongside the maintenance of pembrolizumab for patients experiencing OP during first-line pembrolizumab-based therapy for mNSCLC demonstrated an acceptable safety profile and favorable outcomes. Data from phase 3 randomized trials are needed to clearly establish the benefits of this strategy in treating oligoprogressive mNSCLC.