TY - JOUR
T1 - 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)
AU - Edelman, Martin J.
AU - Redman, Mary W.
AU - Albain, Kathy S.
AU - McGary, Eric C.
AU - Rafique, Noman M.
AU - Petro, Daniel
AU - Waqar, Saiama N.
AU - Minichiello, Katherine
AU - Miao, Jieling
AU - Papadimitrakopoulou, Vassiliki A.
AU - Kelly, Karen
AU - Gandara, David R.
AU - Herbst, Roy S.
N1 - Funding Information:
Disclosure: Dr. Edelman reports grants from Apexigen, Merck, and Bristol-Myers Squibb; personal fees from Armo, BerGen Bio, Syndax, WindMil Therapeutics, and Bristol-Myers Squibb; and stock options from Biomarker Strategies outside the submitted work. Dr. Albain has received personal fees from Novartis, Pfizer, Genomic Health, Myriad, and Genentech/Roche and served as the chair of the independent data monitoring committee of a breast cancer phase III trial for Puma outside of the submitted work. Dr. Waqar reports grants from 1 UM1 CA186704-01 and fees to her institution for serving as a principal investigator from F. Hoffmann-La Roche Ltd, Ariad, Pfizer Pharmaceuticals, Hengrui Therapeutics, Xcovery, EMD Serono Research and Development Institute, Checkpoint Therapeutics, Genentech, Lilly, Stemcentrx, Ignyta, Bristol-Myers Squibb Pharmaceutical, Synermore Biologics, Novartis Pharmaceuticals Corporation, Merck and Company, NewLink Genetics Corporation, and Celegene outside the submitted work. Dr. Papadimitrakopoulou reports service on advisory boards for Nektar Therapeutics, AstraZeneca Pharmaceuticals, Arrys Therapeutics, Merck and Company, Loxo Oncology, Araxes Pharma, F.Hoffman-LaRoche, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Takeda Pharmaceuticals, AbbVie, TRM Oncology, Exelixis, and Tesaro and research funding and grants from Eli Lilly and Company, Novartis, Merck, AstraZeneca Pharmaceuticals, F. Hoffman-La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, and Incyte. Dr. Kelly reports personal fees from AstraZeneca and Bristol-Myers Squibb and grants and personal fees from Genentech and Pfizer outside the submitted work. Dr. Gandara reports consulting for Pfizer during the study. Dr. Herbst reports personal fees from AbbVie Pharmaceuticals, Biodesix, Bristol-Myers Squibb, EMD Serrano, Genentech/Roche, Heat Biologics, Jun Shi Pharmaceuticals, Loxo Oncology, Nektar, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Tesaro, Neon Therapeutics, and Infinity Pharmaceuticals and grants and personal fees from AstraZeneca, Eli Lilly and Company, and Merck and Company outside the submitted work. The remaining authors declare no conflict of interest.This research was supported in part by National Institutes of Health/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, CA180868, CA189821, CA189812, CA180801, CA189830, CA189872, CA180846, CA189873, CA 189822, CA 189809, CA180828, CA180834, CA190002, CA189954, CA180818, CA180826, CA46368, CA46282, and CA11083 and by Amgen, AstraZeneca, Bristol-Myers Squibb Company, Genentech, and Pfizer through the Foundation for the National Institutes of Health in partnership with Friends of Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
This research was supported in part by National Institutes of Health / National Cancer Institute grants CA180888 , CA180819 , CA180820 , CA180821 , CA180868 , CA189821 , CA189812 , CA180801 , CA189830 , CA189872 , CA180846 , CA189873 , CA 189822 , CA 189809 , CA180828 , CA180834 , CA190002 , CA189954 , CA180818 , CA180826 , CA46368 , CA46282 , and CA11083 and by Amgen, AstraZeneca, Bristol-Myers Squibb Company, Genentech, and Pfizer through the Foundation for the National Institutes of Health in partnership with Friends of Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 International Association for the Study of Lung Cancer
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - Cell cycle gene alteration
KW - Cyclin-dependent kinase
KW - Lung cancer
KW - Master protocol
KW - Squamous NSCLC
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85070492538&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2019.06.027
DO - 10.1016/j.jtho.2019.06.027
M3 - Article
C2 - 31302234
AN - SCOPUS:85070492538
SN - 1556-0864
VL - 14
SP - 1853
EP - 1859
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 10
ER -