Phase I study of palbociclib with cisplatin or carboplatin in the management of patients with advanced pancreatic cancer.

IF 4.2 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2025-10-01 DOI:10.1093/oncolo/oyaf284

Olatunji B Alese, Robert Donald Harvey, Christina Wu, Elise Hitron, Hannah Collins, Suzanne Scott, Conor Steuer, Mehmet A Bilen, Bradley C Carthon, Jeffrey M Switchenko, Suresh S Ramalingam, Taofeek K Owonikoko

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引用次数: 0

Abstract

Importance: The addition of agents targeting critical signal mediators of cancer cell proliferation such as cyclin-dependent kinases (CDK) potentiates the efficacy of platinum chemotherapy.ObjectiveTo determine the safety and efficacy of palbociclib combined with cisplatin (cis) or carboplatin (carbo) in advanced solid malignanciesDesignEnrollment on dose escalation (part I) proceeded using the Bayesian adaptive design Escalation with Overdose Control (EWOC).SettingSingle institution investigator initiated trial.

Participants: Patients with any advanced cancer after at least one prior therapy were enrolled on dose escalation to determine recommended phase II doses (RP2D). Expansion cohorts were then opened for pancreaticobiliary tract cancers.InterventionEscalating doses of palbociclib in combination with different doses of cisplatin or carboplatin.Main Outcomes and MeasuresPrimary endpoint was objective response rate (ORR). Secondary endpoints included safety, overall survival (OS), and progression-free survival (PFS).

Results: We enrolled 39 patients on dose escalation (part I) and 32 additional patients on dose expansion (part II). RP2D of palbociclib 100 mg on Day 2-22 + Cisplatin (cis) 60 mg/m2 IV on Day 1 Q4W (Arm A); and palbociclib 75 mg on Day 2-22 + Carboplatin (carbo) AUC 6 IV on Day 1 Q4W (Arm B). ORR for Part I were 12.5% (Arm A) and 25% (Arm B). Median PFS and OS for dose expansion were 2.1 and 4.9 months, respectively. For PDAC, mPFS was 1.9 months (95% CI: 1.7, 2.4), and OS was 3.7 months (95% CI: 2.7, 5.7). Most common treatment-related adverse events (TRAEs-all grade %): Arm A-neutropenia (66%), thrombocytopenia (26%), nausea, fatigue, and anemia (20% each); Arm B-neutropenia (64.7%), thrombocytopenia (53%), and anemia (29%). There were no grade 4-5 TRAEs.

Conclusions and relevance: The combination of palbociclib with cisplatin or carboplatin had an acceptable safety profile and clinical responses in some treatment refractory advanced cancers. There was no objective response, but about half of PDAC patients had disease stabilization. Additional efforts are needed to exploit CDK abnormalities in these patients. Clinical trial registration number: NCT02897375.

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帕博西尼联合顺铂或卡铂治疗晚期胰腺癌的一期研究

背景：加入靶向癌细胞增殖关键信号介质的药物，如细胞周期蛋白依赖激酶（CDK），增强了铂化疗的疗效。患者和方法：经过至少一次既往治疗的任何晚期癌症患者纳入剂量递增以确定推荐的II期剂量（RP2D）。扩大队列然后开放胰胆道（PBT）癌症。主要终点为客观缓解率（ORR）。次要终点包括安全性、总生存期（OS）、无进展生存期（PFS）。结果：我们纳入了39例剂量递增组和32例剂量扩大组。Palbociclib 100mg给D2-22 + cis 60mg /m2 IV给D1 Q4W （A组）；帕博西尼75 mg D2-22 +碳AUC 6 IV D1 Q4W（组B）。第一部分的ORR分别为12.5% （A组）和25% （B组）。剂量扩大的中位PFS和OS分别为2.1和4.9个月。对于PDAC， mPFS为1.9个月（95% CI: 1.7, 2.4）， OS为3.7个月（95% CI: 2.7, 5.7）。最常见的治疗相关不良事件（TRAEs-all grade %）： Arm -a中性粒细胞减少症（66%）、血小板减少症（26%）、恶心、疲劳和贫血（各20%）；Arm B-中性粒细胞减少症（64.7%），血小板减少症（53%）和贫血（29%）。无4 ~ 5级TRAEs。结论：帕博西尼联合顺铂或卡铂治疗一些难治性晚期癌症具有可接受的安全性和临床反应。没有客观反应，但大约一半的PDAC患者病情稳定。需要进一步的努力来利用这些患者的CDK异常。临床试验信息：NCT02897375。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.