A retrospective analysis of the efficacy of immunotherapy in metastatic soft-tissue sarcomas

Varun Monga, Keith M. Skubitz, Seth Maliske, Sarah L. Mott, Hilary Dietz, Angela C. Hirbe, Brian A. Van Tine, Peter Oppelt, Scott Okuno, Steven Robinson, Madeline O’connor, Mahesh Seetharam, Steven Attia, John Charlson, Mark Agulnik, Mohammed Milhem

Research output: Contribution to journalArticlepeer-review

Abstract

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled. Logistic and Cox regression models were applied to determine the effect of patient characteristics, prior treatment, and baseline factors on achieving the best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by the treating physician. Eighty-eight patients with two median prior therapies received checkpoint inhibitors. Treatments included pembrolizumab in 47, nivolumab in 6, ipilimumab in 1, combination ipilimumab/nivolumab in 27, and other combination immunotherapies in 7 patients. Immunotherapy was discontinued in 54 patients—72.2% for progression, 16.7% for toxicity, and 11.1% for other reasons. Median progression-free survival (PFS) was 4.1 months and median overall survival was 19.1 months. One patient with undifferentiated pleomorphic sarcoma (UPS) achieved a CR, while 20 patients had a PR, including 7 UPS, 9 leiomyosarcoma (LMS), and 1 each with alveolar soft part sarcoma, fibroblastic sarcoma, sclerosing epithelioid fibrosarcoma, and myxofibrosarcoma. Forty-five percent (9 of 20) of LMS patients achieved a PR. Twenty-eight patients had SD. Our results confirm the activity and safety of anti-PD-1 therapy in metastatic STS. A notable response rate was observed in UPS and LMS.

Original languageEnglish (US)
Article number1873
Pages (from-to)1-10
Number of pages10
JournalCancers
Volume12
Issue number7
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
Conflicts of Interest: We have full control of all primary data and we agree to allow the journal to review their data if requested. Varun Monga: Research funding and travel expenses from Deciphera. Research funding from Orbus Therapeutics, Immuno cellular. Keith Skubitz: No disclosures. Seth Maliske: No disclosures. Sarah L. Mott: No disclosures. Angela C. Hirbe: No disclosures. Brian Van Tine: Basic Science Grant Funding from Pfizer, Tracon, and Merck; consulting fees from Epizyme, Lilly, CytRX, Janssen, Immune Design, Daiichi, Sankyo, Plexxicon, Bayer and Adaptimmune; speaking fees from Caris, Janseen and Lilly; Travel support from Lilly. Peter Oppelt: Speakers Bureau: Bristol Myers Squibb, Merck, Eisai. Hillary Dietz: No disclosures. Scott Okuno: No disclosures. Steven Robinson: Research funding and travel expenses from TRACON and BTG International Advisory Board with honoraria to the institution. Madeline OConnor: No disclosures. Mahesh Seetharam: No disclosures. Steven Attia: Desmoid Tumor Research Foundation, Research funding from AB Science, TRACON Pharma, CytRx Corporation, Bayer, Novartis, Daiichi Sankyo, Lilly, Immune Design, Karyopharm, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Merck, Philogen, Gradalis, Deciphera, Takeda, Incyte, Springworks, Adaptimmune, Advenchen laboratories, Bavarian Nordic, BTG, PTC therapeutics, GlaxoSmithKline, FORMA Therapeutics. John Charlson: No disclosures. Mark Agulnik: Consulting or Advisory Role: Bayer, Immune Design, Lilly, Novartis. Speaker’s Bureau: Janssen Pharmaceuticals, Eisai, BMS, Bayer. Mohammed Milhem: Research funding from Amgen, Novartis, Merck, Pfizer, ER Squibb & Sons, Prometheus. Honoraria from Blueprint Medicine, Immunocore, Amgen, Trieza. Consulting or advisory role Blueprint Medicine, Amgen, Immunocore, Trieza.

Funding Information:
National Cancer Institute 3P30CA086862-14S1, National Center of Advancing Translational Sciences UL1TR002537, Foundation for National Institute of Health K12 CA90628, Robert Wood Johnson Foundation Center for Health Policy 75207.

Keywords

  • Anti CTLA-4
  • Anti-PD1
  • Efficacy
  • Immunotherapy
  • Sarcoma

PubMed: MeSH publication types

  • Journal Article

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