Literature DB >> 31302234

SWOG S1400C (NCT02154490)-A Phase II Study of Palbociclib for Previously Treated Cell Cycle Gene Alteration-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy).

Martin J Edelman1, Mary W Redman2, Kathy S Albain3, Eric C McGary4, Noman M Rafique5, Daniel Petro6, Saiama N Waqar7, Katherine Minichiello2, Jieling Miao2, Vassiliki A Papadimitrakopoulou8, Karen Kelly9, David R Gandara9, Roy S Herbst10.   

Abstract

OBJECTIVE: Lung-MAP (SWOG S1400) is a master platform trial assessing targeted therapies in squamous NSCLC. The objective of study C (S1400C) was to evaluate the response rate to palbociclib, a cyclin-dependent kinase 4 and cyclin-dependent kinase 6 inhibitor, in patients with cell cycle gene abnormalities.
METHODS: Patients with squamous NSCLC, a performance status of 0 to 2, and normal organ function who had progressed after at least one prior platinum-based chemotherapy with cyclin-dependent kinase 4 gene (CDK4) or cyclin D1 gene (CCND1), cyclin D2 gene (CCND2), or cyclin D3 gene (CCND3) amplifications on tumor specimens were eligible. The study was originally designed as a phase II/III trial comparing palbociclib with docetaxel, but it was modified to a single-arm phase II trial with the primary end point of response when immunotherapy was approved. If two or fewer responses were seen in the first 20 patients, then the study would cease enrollment.
RESULTS: A total of 88 patients (9% of patients screened) were assigned to S1400C, and 53 patients enrolled (including 17 to receive docetaxel). One patient who had been registered to receive docetaxel was re-registered to receive palbociclib after progression while taking docetaxel. The frequencies of cell cycle gene alterations in the eligible patients taking palbociclib (n = 32) were as follows: CCND1, 81% (n = 26); CCND2, 9% (n = 3); CCND3, 6% (n = 2); and CDK4, 3% (n = 1). In all, 32 eligible patients received palbociclib. There were two partial responses (response rate 6% [95% confidence interval (CI): 0%-15%]), both with CCND1 amplification. Twelve patients had stable disease (38% [95% CI: 21%-54%]). The median progression-free survival was 1.7 months (95% CI: 1.6-2.9 months) and the median overall survival was 7.1 months (95% CI: 4.2-12.5).
CONCLUSION: Palbociclib as monotherapy failed to demonstrate the prespecified criteria for advancement to phase III testing.
Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Cell cycle gene alteration; Cyclin-dependent kinase; Lung cancer; Master protocol; Squamous NSCLC; Targeted therapy

Year:  2019        PMID: 31302234      PMCID: PMC6764876          DOI: 10.1016/j.jtho.2019.06.027

Source DB:  PubMed          Journal:  J Thorac Oncol        ISSN: 1556-0864            Impact factor:   15.609


  14 in total

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Review 4.  Cyclin-dependent kinase pathways as targets for cancer treatment.

Authors:  Geoffrey I Shapiro
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Authors: 
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