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Clin Lung Cancer. 2018 Sep;19(5):e567-e574. doi: 10.1016/j.cllc.2018.03.016. Epub 2018 Mar 23.

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.

Author information

1
Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC. Electronic address: gg496@georgetown.edu.
2
Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR.
3
Division of Oncology, Washington University Medical School, St Louis, MO.
4
Vall d'Hebron University Hospital, Barcelona, Spain.
5
12 de Octubre University Hospital, Madrid, Spain.
6
Incyte Corporation, Wilmington, DE.
7
Highlands Oncology Group, Fayetteville, AR.

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/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.

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.

KEYWORDS:

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

PMID:
29681434
DOI:
10.1016/j.cllc.2018.03.016

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