Title

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.

Authors

Giuseppe Giaccone
Rachel E Sanborn, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR.Follow
Saiama N Waqar
Alex Martinez-Marti
Santiago Ponce
Huiling Zhen
Gerard Kennealey
Susan Erickson-Viitanen
Eric Schaefer

Document Type

Article

Publication Date

9-1-2018

Keywords

JAK1; JAK2; Janus kinase (JAK); Modified Glasgow prognostic score; Signal transducers and activators of transcription (STAT)

Abstract

BACKGROUND: 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).

PATIENTS AND METHODS: 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/m

RESULTS: 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).

CONCLUSION: 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.

Clinical Institute

Cancer

Department

Oncology

Department

Pulmonary Medicine

Department

Earle A. Chiles Research Institute

Recommended Citation

Giaccone, Giuseppe; Sanborn, Rachel E; Waqar, Saiama N; Martinez-Marti, Alex; Ponce, Santiago; Zhen, Huiling; Kennealey, Gerard; Erickson-Viitanen, Susan; and Schaefer, Eric, "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." (2018). Articles, Abstracts, and Reports. 823.
https://digitalcommons.providence.org/publications/823