Palbociclib in Patients With Head and Neck Cancer and Other Tumors With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

IF 5.3 2区 医学 Q1 ONCOLOGY JCO precision oncology Pub Date : 2024-10-01 Epub Date: 2024-10-16 DOI:10.1200/PO-24-00477
Francis P Worden, Evan Pisick, Michael Rothe, Pam K Mangat, Elizabeth Garrett-Mayer, Maged F Khalil, Daniel R Carrizosa, Jessica R Bauman, Rom S Leidner, Herbert L Duvivier, Siqing Fu, Min S Park, Kathleen J Yost, Carmen J Calfa, Alissa S Marr, Ani S Balmanoukian, Deepti Behl, Timothy L Cannon, Lisle Nabell, Steven Francis Powell, Ramya Thota, Dominique C Hinshaw, Abigail Gregory, Gina N Grantham, Susan Halabi, Richard L Schilsky
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Abstract

Purpose: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Two cohorts of patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-mutated tumors treated with palbociclib are reported: one with head and neck cancer (HNC) with both squamous and nonsquamous cell histologies, and one with histology-pooled (HP) cancers.

Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. For the HNC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included OR, safety, progression-free survival, overall survival, duration of response, and duration of SD.

Results: Seventy patients with HNC (N = 28) or HP cancers (N = 42) were treated with palbociclib. For the HNC cohort, DC and OR rates were 40% (one-sided 90% CI, 27 to 100) and 4% (95% CI, <1 to 18), respectively. The null hypothesis was rejected (P = .002). For the HP cohort, DC and OR rates were 13% (one-sided 90% CI, 6 to 100) and 5% (95% CI, <1 to 17), respectively. The null hypothesis was not rejected. Thirty-one of 70 patients experienced treatment-related grade 3 to 4 adverse events (AEs) or serious AEs, the most common including neutropenia, thrombocytopenia, and leukopenia.

Conclusion: Palbociclib met prespecified criteria to declare a signal of activity in patients with HNC with CDKN2A alterations, but not in the HP cohort.

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帕博西尼(Palbociclib)治疗头颈癌及其他CDKN2A基因改变的肿瘤患者:靶向药物和剖析利用登记研究的结果。
目的:靶向药物和剖析利用注册是一项II期篮子试验,评估市售靶向药物在晚期癌症和可靶向基因组改变患者中的抗肿瘤活性。本文报告了两组接受帕博西尼(palbociclib)治疗的细胞周期蛋白依赖性激酶抑制剂2A(CDKN2A)突变肿瘤患者:一组是鳞状细胞和非鳞状细胞组织学的头颈癌(HNC)患者,另一组是组织学汇集(HP)癌症患者:符合条件的患者均患有可测量的疾病、东部合作肿瘤学组(Eastern Cooperative Oncology Group)表现为 0-2 级、器官功能正常且无标准治疗方案。主要终点是疾病控制(DC),即至少持续 16 周以上的客观反应(OR)或疾病稳定(SD)。对于HNC队列,采用西蒙两阶段设计,疾病控制率为15%对35%(功率=0.85;α=0.10)。对于HP队列,如果单侧90% CI的下限>15%,则拒绝直流电率为15%的零假设。次要终点包括OR、安全性、无进展生存期、总生存期、反应持续时间和SD持续时间:70例HNC(28例)或HP癌(42例)患者接受了palbociclib治疗。在HNC队列中,DC和OR率分别为40%(单侧90% CI,27至100)和4%(95% CI,P = .002)。HP队列中,DC和OR率分别为13%(单侧90% CI,6至100)和5%(95% CI,P = .002):Palbociclib在CDKN2A改变的HNC患者中符合宣布活性信号的预设标准,但在HP队列中不符合标准。
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