TY - JOUR
T1 - 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
AU - Giaccone, Giuseppe
AU - Sanborn, Rachel E.
AU - Waqar, Saiama N.
AU - Martinez-Marti, Alex
AU - Ponce, Santiago
AU - Zhen, Huiling
AU - Kennealey, Gerard
AU - Erickson-Viitanen, Susan
AU - Schaefer, Eric
N1 - Funding Information:
The authors thank the patients and their families, the investigators, and the site personnel who participated in this study. This study was sponsored by Incyte Corporation (Wilmington, DE). Medical writing assistance was provided by Felicity Leigh, PhD, on behalf of Evidence Scientific Solutions Inc, and funded by Incyte.
Funding Information:
Dr Giaccone has served as an advisor to AstraZeneca, Bristol-Myers Squibb, and G1 Therapeutics, and has received research funding from Eli Lilly and Karyopharm. Dr Sanborn has received honoraria from AstraZeneca, served as an advisor to AbbVie, ARIAD/Takeda, AstraZeneca, Celldex, Genentech/Roche, Peregrine Pharmaceuticals, and Seattle Genetics, and received research funding from Merck (investigator sponsored trial), BMS (institutional support), and MedImmune (institutional support). Dr Erickson-Viitanen is a consultant to Incyte, and holds Incyte stock and other ownership interests. Dr Zhen is an employee and holds Incyte stocks. Dr Kennealey is a consultant to Incyte. The remaining authors have stated that they have no conflicts of interest.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9
Y1 - 2018/9
N2 - This was a 2-part trial of ruxolitinib plus pemetrexed/cisplatin for nonsquamous non–small-cell lung cancer. Part 1 (15 patients) identified ruxolitinib 15 mg twice daily as dose of choice, with an acceptable safety profile. Because the study was terminated early, interpretation of efficacy data from part 2 is limited (double-blind; at termination, 39 and 37 patients were randomized to ruxolitinib and placebo, respectively). 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 2 intravenous, day 1) and cisplatin (75 mg/m 2 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.
AB - This was a 2-part trial of ruxolitinib plus pemetrexed/cisplatin for nonsquamous non–small-cell lung cancer. Part 1 (15 patients) identified ruxolitinib 15 mg twice daily as dose of choice, with an acceptable safety profile. Because the study was terminated early, interpretation of efficacy data from part 2 is limited (double-blind; at termination, 39 and 37 patients were randomized to ruxolitinib and placebo, respectively). 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 2 intravenous, day 1) and cisplatin (75 mg/m 2 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.
KW - JAK1
KW - JAK2
KW - Janus kinase (JAK)
KW - Modified Glasgow prognostic score
KW - Signal transducers and activators of transcription (STAT)
UR - http://www.scopus.com/inward/record.url?scp=85045887819&partnerID=8YFLogxK
U2 - 10.1016/j.cllc.2018.03.016
DO - 10.1016/j.cllc.2018.03.016
M3 - Article
C2 - 29681434
AN - SCOPUS:85045887819
SN - 1525-7304
VL - 19
SP - e567-e574
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 5
ER -