A Phase II Study of Durvalumab, Doxorubicin, and Ifosfamide in Recurrent and/or Metastatic Pulmonary Sarcomatoid Carcinoma (KCSG LU-19-24)

Abstract

Background Pulmonary sarcomatoid carcinomas (PSCs) are rare, aggressive tumors with a poor prognosis. Conventional chemotherapy shows limited efficacy, whereas immune checkpoint inhibitors and doxorubicin have shown potential. This study evaluated the efficacy and safety of durvalumab, doxorubicin, and ifosfamide in recurrent and/or metastatic PSC. Patients and Methods Patients with recurrent or metastatic PSC received durvalumab (1500 mg, day 1), doxorubicin (20 mg/m² intravenously, days 1-3), and ifosfamide (1.5 g/m² intravenously with mesna, days 2-4) every 3 weeks for up to four cycles, followed by durvalumab monotherapy until disease progression or unacceptable toxicity, for up to 12 months. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and toxicity. Results The study was prematurely terminated due to low recruitment rates, with 20 patients enrolled (15 male, 5 female; median age: 63.5 years). Among 18 evaluable cases, 16 (88.9%) were programmed death-ligand 1 positive. Six patients (30.0%) had prior palliative chemotherapy. ORR was 35.0% (95% CI, 17.7%-55.8%). The median DOR was 5.3 months (95% CI, 1.7-not estimated). After a median follow-up of 7.0 months (1.2-37.6), the median PFS and OS were 4.8 months (95% CI, 2.0-6.5) and 9.4 months (95% CI, 5.5-26.8), respectively. Adverse events (AEs) occurred in 19 patients, with serious AEs in 10 patients. Conclusion Durvalumab combined with doxorubicin and ifosfamide suggested clinical activity in recurrent and/or metastatic PSC. Larger studies are warranted to confirm benefits and refine treatment strategies. © 2025 The Authors.