A Placebo-Controlled Phase II Study of Ruxolitinib in Combination With Pemetrexed and Cisplatin for First-Line Treatment of Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer and Systemic Inflammation

Dysregulation of the Janus kinase (JAK)/signal transducers and activators of transcription pathway contributes to abnormal inflammatory responses and poor prognosis in non-small-cell lung cancer (NSCLC). We evaluated the JAK1/JAK2 inhibitor ruxolitinib plus pemetrexed/cisplatin first-line in patients with stage IIIB/IV or recurrent nonsquamous NSCLC with systemic inflammation (modified Glasgow prognostic score [mGPS] 1/2).Part 1 was an open-label, safety run-in, in which we assessed ruxolitinib (15 mg twice daily [b.i.d.]) plus pemetrexed (500 mg/m2 intravenous, day 1) and cisplatin (75 mg/m2 intravenous, day 1). Ruxolitinib dose selection for part 2 required <3 dose-limiting toxicities (DLTs) for 9 evaluable patients. In part 2 patients were randomized to ruxolitinib or placebo (each plus pemetrexed/cisplatin). The trial terminated early for reasons unrelated to this trial.Fifteen patients enrolled in part 1 (median age, 64 years; 80% male, 80% mGPS 1) received ruxolitinib 15 mg b.i.d. plus pemetrexed/cisplatin. Median treatment duration was 140 days and no DLTs occurred in 11 evaluable patients. No new safety concerns arose when ruxolitinib was combined with pemetrexed/cisplatin. At study termination, 39 patients were randomized to ruxolitinib and 37 to placebo in part 2. Median treatment duration was 43 days. Response rate was 31% (12 of 39) with ruxolitinib and 35% (13 of 37) with placebo (all partial responses).Ruxolitinib 15 mg b.i.d. had an acceptable safety profile in combination with pemetrexed/cisplatin asfirst-line treatment of patients with stage IIIB/IV or recurrent nonsquamous NSCLC and systemic inflammation. Early study termination limited the interpretation of efficacy data in the randomized phase II part of the study.