A Phase 2 Study of Pembrolizumab Combined with Chemoradiotherapy as Initial Treatment for Anaplastic Thyroid Cancer

Ashish V. Chintakuntlawar, Jun Yin, Robert Foote, Jan L. Kasperbauer, Michael Rivera, Erik Asmus, Nina I. Garces, Jeffrey R. Janus, Minetta Liu, Daniel J Ma, Eric J. Moore, John C. Morris, Michelle Neben-Wittich, Daniel L. Price, Katharine A. Price, Mabel M Ryder, Kathryn M. Van Abel, Crystal Hilger, Eleyna Samb, Keith Christophe Bible

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival (OS) of ∼6 months. We previously reported high PD-1/PDL-1 staining in ATC, raising the possibility of the productive application of the immunotherapeutic pembrolizumab. However, having found pembrolizumab to anecdotally have limited single-agent activity in ATC, we sought to alternatively define whether pembrolizumab might synergistically combine with chemoradiotherapy as initial ATC therapy. Methods: An investigator-initiated therapeutic phase 2 trial of pembrolizumab, 200 mg intravenously (IV) every 3 weeks, combined with chemoradiotherapy (docetaxel/doxorubicin, 20 mg/m2 each IV weekly plus volumetric modulated arc therapy) was initiated as frontline therapy (with or without surgery) in ATC to assess efficacy and toxicities. Six-month OS was selected as the primary endpoint using a Simon's optimal design with interim analysis (targeting accrual of 25 patients; Cohort A: prior resection, Cohort B: no resection). Based on a prior patient cohort-treated similarly, but without pembrolizumab, the design was such that, if 6-month true survival is 75%, the probability of declaring the approach worthy of further pursuit would be 91%. Results: Three patients were enrolled, two with rapidly enlarging unresectable neck masses. Early tumor responses were favorable in all three, and all three satisfactorily completed: intended radiotherapy, preceding and radiotherapy-concurrent pembrolizumab, and concurrent chemoradiotherapy. However, all three patients died <6 months following therapy initiation - one from pulmonary metastases and two from otherwise unexpected fatal pulmonary complications occurring subsequent to chemoradiotherapy completion - prompting study closure. Conclusions: Although initially tolerated and effective in terms of locoregional disease control, disappointing survival outcomes compared with historical controls raise uncertainty that the piloted approach merits further pursuit in ATC.

Original languageEnglish (US)
Pages (from-to)1615-1622
Number of pages8
JournalThyroid
Volume29
Issue number11
DOIs
StatePublished - Nov 2019

Keywords

  • anaplastic thyroid cancer
  • chemoradiotherapy
  • immunotherapy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Chintakuntlawar, A. V., Yin, J., Foote, R., Kasperbauer, J. L., Rivera, M., Asmus, E., Garces, N. I., Janus, J. R., Liu, M., Ma, D. J., Moore, E. J., Morris, J. C., Neben-Wittich, M., Price, D. L., Price, K. A., Ryder, M. M., Van Abel, K. M., Hilger, C., Samb, E., & Bible, K. C. (2019). A Phase 2 Study of Pembrolizumab Combined with Chemoradiotherapy as Initial Treatment for Anaplastic Thyroid Cancer. Thyroid, 29(11), 1615-1622. https://doi.org/10.1089/thy.2019.0086