Locally advanced NSCLC: overview of real-world pattern of recurrence in durvalumab era (LEOPARD trial)

Background: Despite the advances introduced by the PACIFIC trial, recurrence after definitive chemoradiotherapy (CRT) followed by durvalumab consolidation remains a significant clinical challenge in unresectable stage III non-small cell lung cancer (NSCLC). This study aims to investigate relapse patterns and outcomes of salvage treatments in a real-world cohort, providing insights for post-progression management. Methods: We performed a retrospective analysis of 166 patients with unresectable stage III NSCLC treated with the PACIFIC regimen across eight Italian centers from January 2018 to December 2021. Recurrences were classified as oligorecurrent (<= 3 lesions amenable to local therapy) or polyrecurrent. The impact of salvage strategies on overall survival (OS) was reported. Results: After a median follow-up of 33 months, 56 % of patients experienced recurrence; among these, 72 % were oligorecurrent. Oligorecurrences predominantly involved the lungs (34 %) and brain (26 %), mostly outside the irradiated field. Median OS was significantly longer in oligorecurrent versus polyrecurrent patients (41 vs. 19 months). Salvage therapies in oligorecurrent patients included radiotherapy (RT) (45 %), chemotherapy (35 %), and CRT (13 %). Median OS was 25 months for those treated with RT alone and 30 months for those receiving CRT. Polyrecurrent patients primarily underwent chemotherapy (77 %) with a median OS of 12 months. Conclusions: Oligorecurrence represented the predominant pattern of relapse post-CRT and durvalumab, associated with improved survival when treated with metastasis-directed therapies. These findings underscore the importance of stratifying recurrence patterns and integrating local salvage treatments, especially RT, in personalized management. Prospective trials are needed to refine salvage strategies and evaluate novel therapeutic combinations.