Durvalumab combined with chemotherapy and Stereotactic Ablative Body Radiotherapy (SABR) in patients with oligometastatic non-small cell lung cancer: a multi-center phase 2 study
Mené sur 35 patients atteints d'un cancer du poumon à petites cellules de stade métastatique, cet essai multicentrique de phase II évalue l’efficacité, du point de vue de la survie sans progression, et la sécurité du durvalumab en combinaison avec une chimiothérapie et une radiothérapie stéréotaxique d'ablation
Purpose: Immunotherapy plus chemotherapy is the standard of care for driver-gene negative metastatic non-small cell lung cancer (NSCLC). Synchronous oligometastatic disease has a better prognosis than extensive metastasis, and the addition of Stereotactic Ablative Radiotherapy (SABR) results in improved efficacy. However, whether the combination of SABR with immunotherapy and platinum-doublet chemotherapy will lead to long-term disease control or even cure for patients remains unclear.
Patients and Methods: This was a multi-center, phase 2, single-arm study to evaluate the efficacy and safety of durvalumab in combination with chemotherapy and SABR for oligometastatic stage IV NSCLC without previous systemic therapy. The primary endpoint was investigator-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors Version 1.1.
Results: Thirty-five patients were enrolled in the study. Twenty-eight (80%) patients received radiotherapy (RT), including 23 (65.7%) received SABR. The median follow-up time was 24.7 months (95% CI, 21.6-27.5). In the full analysis set (n=35), the median PFS (mPFS) was 10.4 months (95% CI, 4.4-26.1), and the two-year PFS rate and overall survival (OS) rate were 38.5% (95% CI, 21.9-54.8%) and 67.7% (95% CI, 49.0-80.7%), respectively. In the per protocol set (n=32), mPFS was 14.6 months (95% CI, 4.7-26.1), and the two-year PFS rate and OS rate were 42.4% (95% CI, 24.3-59.4%) and 70.8% (95% CI, 51.2-83.8%), respectively. The subgroup analysis showed that the mPFS was 24.3 months (95%CI, 7.6-NE) with SABR vs 3.1 months (95% CI, 1.4-4.7) without SABR (HR, 0.2; 95% CI, 0.09-0.5; P<0.001). Grade 3 or higher treatment related adverse events (TRAEs) and immune-mediated AEs (imAEs) were reported in 57.1% (20/35) and 25.7% (9/35) of patients, respectively.
Conclusions: In oligometastatic NSCLC, the combination of durvalumab, chemotherapy and SABR was effective and tolerable. Patients who did not experience disease progression after prior systemic therapy and received SABR might have optimal outcomes.
International Journal of Radiation Oncology, Biology, Physics , résumé, 2025