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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

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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.

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Acknowledgements

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Credit classification

Conceptualization: Paul Swiecicki, Chad Brenner, Francis Worden.

Data curation: Apurva Bhangale, Emily Bellile, Paul Swiecicki.

Formal analysis: Apurva Bhangale, Chad Brenner, Emily Bellile, Paul Swiecicki.

Methodology: Chad Brenner, Emily Bellile, Paul Swiecicki.

Resources: Chad Brenner, Paul Swiecicki, Francis Worden, Greg Durm.

Writing - original draft: Paul Swiecicki, Emily Bellile, Apurva Bhangale, Chad Brenner.

Writing - review and editing: Paul Swiecicki, Emily Bellile, Chad Brenner, Francis Worden, Greg Durm

Funding

Pfizer Inc. provided an independent research grant for this trial. A.B. and J.C.B. received partial support from ACS grant: 132034-RSG-18-062-01-TBG.

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Authors and Affiliations

  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

    Paul L. Swiecicki & Francis P. Worden

  2. Department of Internal Medicine, Division of Hematology/Oncology, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI, USA

    Paul L. Swiecicki

  3. Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA

    Paul L. Swiecicki, J. Chad Brenner & Francis P. Worden

  4. Department of Internal Medicine, Division of Hematology/Oncology, Indiana University, Indianapolis, IN, USA

    Greg Durm

  5. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA

    Emily Bellile

  6. Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, University of Michigan Health System, Ann Arbor, MI, USA

    Apurva Bhangale & J. Chad Brenner

  7. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA

    J. Chad Brenner

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Correspondence to Paul L. Swiecicki.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals.

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Written informed consent was obtained from all individual participants included in the study.

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Pfizer Inc. provided an independent research grant for this trial. A.B. and J.C.B. received partial support from ACS grant: 132034-RSG-18-062-01-TBG.

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Swiecicki, P.L., Durm, G., Bellile, E. et al. 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. Invest New Drugs 38, 1550–1558 (2020). https://doi.org/10.1007/s10637-020-00898-2

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