2019 ASCO Annual Meeting!
Session: Head and Neck Cancer
Type: Poster Session
Time: Saturday June 1, 1:15 PM to 4:15 PM
Location: Hall A
Session: Head and Neck Cancer
Type: Poster Discussion Session
Time: Saturday June 1, 4:30 PM to 6:00 PM
Palbociclib plus cetuximab versus placebo plus cetuximab in platinum-resistant, cetuximab-naive, HPV-unrelated head and neck cancer: A double-blind randomized phase II trial (PALATINUS).
Head and Neck Cancer
2019 ASCO Annual Meeting
Poster Board Number:
Poster Discussion Session (Board #2)
J Clin Oncol 37, 2019 (suppl; abstr 6013)
Author(s): Douglas Adkins, Jin-Ching Lin, Assuntina Gesualda Sacco, Jessica C. Ley, Peter Oppelt, Qi Shen, Kenneth Alan Kern, Holger C. Thurm, Shaw-Ling Wang, Jean-Francois Martini, Justin Hoffman, Bohuslav Melichar, Makoto Tahara; Division of Medical Oncology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO; Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; University of California San Diego Moores Cancer Center, San Diego, CA; Pfizer Inc, Collegeville, PA; Pfizer Inc, New York, NY; Pfizer Inc, San Diego, CA; Fakultni Nemocnice Olomouc/Onkologicka Klinika, Pavlova, Czech Republic; National Cancer Center Hospital East, Kashiwa, Japan
Background: Cetuximab monotherapy results in a median overall survival (OS) of approximately 6 months (mo) in platinum-resistant recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). HNSCC unrelated to human papillomavirus (HPV) is driven by hyperactivation of the CDK4/6 and cyclin D1 (CD1) regulatory complex, resulting in cell cycle progression and tumor growth, suggesting that CDK4/6 inhibition can be a rational therapeutic strategy in this setting. Palbociclib (PAL) is a selective CDK4/6 inhibitor that may reverse cetuximab resistance by countering the actions of deregulated CD1. PAL plus an epidermal growth factor receptor inhibitor synergistically reduced cell viability of HPV-unrelated HNSCC cell lines. In a single-arm, multicenter trial of platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC, PAL in combination with cetuximab resulted in a median OS of 9.5 mo. Methods: In a double-blind randomized phase II trial, patients (pts) with platinum-resistant, cetuximab-naïve, HPV-unrelated HNSCC were treated with cetuximab plus either PAL (arm A) or placebo (arm B). Pts were stratified by performance status (PS) and prior immunotherapy (IT). 120 pts were required for 1:1 randomization to have ≥ 80% power to detect a hazard ratio (HR) of 0.6 (corresponding to a median OS of 10 mo in arm A and 6 mo in arm B) using a 1-sided log-rank test P=0.10). Key secondary endpoints included progression-free survival (PFS), adverse events (AEs), and p16 status. Results: Pts (n=125) were randomized (arm A, 65; arm B, 60). PS and prior IT were balanced between the arms. Median (95% CI) follow-up for OS was 15.9 (15.0–19.4) mo. Median OS was 9.7 (7.3–13.9) mo in arm A and 7.8 (6.7–10.6) mo in Arm B (stratified by PS: HR=0.82 [95% CI, 0.54–1.25], P=0.18). Median PFS was 3.9 mo in arm A and 4.6 mo in arm B (stratified by PS: HR=1.00 [0.7–1.5], P=0.5). Hematologic AEs were more common in arm A. Only 11 pts (9%) received IT after being treated on the trial. Conclusions: Among pts with platinum-resistant, HPV-unrelated HNSCC, PAL plus cetuximab resulted in a trend of prolongation of median OS compared with cetuximab. Clinical trial information: NCT02499120