A multi-center phase II trial evaluating the efficacy of palbociclib in combination with carboplatin for the treatment o
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PHASE II STUDIES
A multi-center phase II trial evaluating the efficacy of palbociclib in combination with carboplatin for the treatment of unresectable recurrent or metastatic head and neck squamous cell carcinoma Paul L. Swiecicki 1,2,3
&
Greg Durm 4 & Emily Bellile 5 & Apurva Bhangale 6 & J. Chad Brenner 3,6,7 & Francis P. Worden 1,3
Received: 4 January 2020 / Accepted: 15 January 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Background Palbociclib is a selective inhibitor of CDK4/6 approved in metastatic breast cancer as well as evidence of activity in malignancies with CDK4-amplifications. Extensive preclinical evidence has demonstrated synergy of CDK4/6 inhibitors with platinum chemotherapy suggesting a potential role for clinical synthetic lethality. Given the sensitivity to platinum therapy as well as the landscape of genomic alterations, concurrent treatment with platinum chemotherapy and palbociclib is of significant interest as a novel treatment approach. Patients and Methods Patients with unresectable, recurrent, or metastatic head and neck cancer (R/M HNC) were enrolled. Eligible patients were required to have no previous treatment with cytotoxic chemotherapy in the recurrent/metastatic setting. This was a multicenter phase II trial in which patients were administered carboplatin in addition to concurrent palbociclib. The primary endpoint of this trial was 12-week disease control rate (DCR). Results Twenty-one patients were enrolled and 18 were evaluable for response. Grade 3/4 treatment related toxicities were seen in 79% of patients of which the most common were related to myelosuppression. 12-week DCR was 33% (5 patients with stable disease, 1 with a partial response). Median progression free survival was 2.9 months (range: 1.2–13.3) and overall survival was 4.6 months (range: 1.4–14.8). Conclusion The combination of carboplatin and palbociclib is associated with significant treatment related toxicity and insufficient anti-tumor activity. Keywords Head and neck neoplasm . Palbociclib . CDK4/6 . Carboplatin . Metastatic head and neck cancer . HNSCC
Introduction Unresectable recurrent or metastatic head and neck cancer (R/M HNC) has a dismal survival and development of targeted therapeutics has been met with little success. Platinum
compounds have been the backbone of therapy with a response rate (RR) of 10–30% to single agent regimens [1, 2]. Until recently, first line chemotherapy consisted of the EXTREME regimen which has a demonstrated RR of 36% and OS of 10.1 months [3]. Given the limited performance status at
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10637-020-00898-2) contains supplementary material, which is available to authorized users. * Paul L. Swiecicki [email protected] 1
Department of Internal Medicine, Division of Hematology/ Oncology, University of Michigan Medical School, 300 N Ingalls St, SPC 5419, Ann Arbor, MI 48109, USA
2
Department of Internal Medicine, Division of Hematology/
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