A phase II study of durvalumab, doxorubicin, and ifosfamide in recurrent and/or metastatic pulmonary sarcomatoid carcinoma (KCSG LU-19-24).

8566 Background: Pulmonary sarcomatoid carcinomas (PSCs) are very rare and aggressive tumors with poor prognosis. While conventional cytotoxic agents have limited efficacy in PSC, immune checkpoint inhibitors or doxorubicin showed potential efficacy. We evaluated the efficacy and safety of durvalumab, doxorubicin, and ifosfamide for recurrent and/or metastatic PSC. Methods: Patients with recurrent or metastatic PSC received durvalumab (1500 mg, day1), doxorubicin (20 mg/m² IV, days 1–3) and ifosfamide (1.5 g/m² IV with mesna, days 2–4) every 3 weeks for up to 4 cycles, followed by durvalumab monotherapy until disease progression or unacceptable toxicity, upto 12 months. The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR) and toxicity. Results: A total of 20 patients (15 male, 5 female) were enrolled, and the median age was 63.5 (range, 44-75). Sixteen (88.9%) of the 18 evaluable cases were PD-L1 positive. Six (30.0%) out of 20 patients had previously received palliative chemotherapy. Among them, 18 patients were evaluable for the primary endpoint. ORR was 35.0% (95% CI, 17.7-55.8%) based on modified RECIST version 1.1. and the median DOR was 5.3 months (95% CI, 1.7-not estimated). After a median follow-up duration of 7.0 months (range, 1.2-37.6), the median PFS and OS were 4.8 months (95% CI, 2.0-6.5 months) and 9.4 months (95% CI, 5.5-26.8 months), respectively. Adverse events (AEs) of any grade were reported in 19 patients with serious AEs in 10 patients. The most common AEs were nausea (9.7%), anemia (7.5%), vomiting (5.4%). No treatment-related deaths were reported. Conclusions: Given its rarity and aggressiveness of PSC, the combination of durvalumab, doxorubicin, and ifosfamide demonstrated promising efficacy in recurrent and/or metastatic cases. Further studies are required to validate these findings and optimize treatment strategies for PSC. Clinical trial information: NCT04224337 .