TY - JOUR
T1 - The Potential for Selective Cyclin-Dependent Kinase 4/6 Inhibition in the Therapy for Head and Neck Squamous Cell Carcinoma
AU - Adkins, Douglas
AU - Ley, Jessica
AU - Cohen, Jared
AU - Oppelt, Peter
N1 - Funding Information:
Several reports cited in this work were funded and/or supported by Pfizer Inc, Eli Lilly, and Company; The Jose Sanchez Medical Research Fund; and Gregory Stubblefield and Nancy Apel, for which we are immensely grateful. The authors thank the participating patients, the head and neck cancer research team at Washington University, and Sarper Toker, MD. They recognize the support of the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri, the Clinical Trials Core, the Biostatistics Shared Resource, and the Center for Biomedical Informatics. The Siteman Cancer Center is supported in part by NCI Cancer Center Support Grant #P30 CA91842.
Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Preclinical data support investigation of selective CDK4/6 inhibition as a therapeutic strategy for human papillomavirus (HPV)-unrelated head and neck squamous cell carcinoma (HNSCC). Phase 1 clinical trials established the feasibility of combining palbociclib with cetuximab in patients with recurrent or metastatic HNSCC. Nonrandomized phase II trials showed that palbociclib plus cetuximab resulted in efficacy outcomes better than cetuximab in biomarker-unselected, platinum-resistant or cetuximab-resistant, HPV-unrelated HNSCC. A double-blind, randomized phase II trial (PALATINUS) evaluated the efficacy of palbociclib or placebo and cetuximab in patients with biomarker-unselected, platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC. Palbociclib and cetuximab did not significantly prolong overall survival compared with placebo and cetuximab. However, correlative biomarker analyses identified that trends for better overall survival with palbociclib and cetuximab were observed in certain prespecified subsets; the largest reduction in risk of death with palbociclib versus placebo and cetuximab occurred in the subset with CDKN2A mutations. Several phase II-III trials are underway investigating palbociclib in biomarker-selected patients with HPV-unrelated locally advanced or recurrent or metastatic HNSCC.
AB - Preclinical data support investigation of selective CDK4/6 inhibition as a therapeutic strategy for human papillomavirus (HPV)-unrelated head and neck squamous cell carcinoma (HNSCC). Phase 1 clinical trials established the feasibility of combining palbociclib with cetuximab in patients with recurrent or metastatic HNSCC. Nonrandomized phase II trials showed that palbociclib plus cetuximab resulted in efficacy outcomes better than cetuximab in biomarker-unselected, platinum-resistant or cetuximab-resistant, HPV-unrelated HNSCC. A double-blind, randomized phase II trial (PALATINUS) evaluated the efficacy of palbociclib or placebo and cetuximab in patients with biomarker-unselected, platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC. Palbociclib and cetuximab did not significantly prolong overall survival compared with placebo and cetuximab. However, correlative biomarker analyses identified that trends for better overall survival with palbociclib and cetuximab were observed in certain prespecified subsets; the largest reduction in risk of death with palbociclib versus placebo and cetuximab occurred in the subset with CDKN2A mutations. Several phase II-III trials are underway investigating palbociclib in biomarker-selected patients with HPV-unrelated locally advanced or recurrent or metastatic HNSCC.
KW - CDK4/6
KW - CDKN2A
KW - HPV-unrelated
KW - head and neck cancer
UR - http://www.scopus.com/inward/record.url?scp=85139373987&partnerID=8YFLogxK
U2 - 10.1097/PPO.0000000000000617
DO - 10.1097/PPO.0000000000000617
M3 - Review article
C2 - 36165726
AN - SCOPUS:85139373987
SN - 1528-9117
VL - 28
SP - 377
EP - 380
JO - Cancer Journal (United States)
JF - Cancer Journal (United States)
IS - 5
ER -