Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma

Sandra P. D’Angelo, Matthias Hunger, Andrew S. Brohl, Paul Nghiem, Shailender Bhatia, Omid Hamid, Janice M. Mehnert, Patrick Terheyden, Kent C. Shih, Isaac Brownell, Céleste Lebbé, Karl D. Lewis, Gerald P. Linette, Michele Milella, Michael Schlichting, Meliessa H. Hennessy, Murtuza Bharmal

Research output: Contribution to journalArticle

Abstract

Background: Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1). Methods: Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i.v. avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or withdrawal. Using conditional landmark analyses, we compared OS in patients with and without confirmed OR (RECIST v1.1). We applied a Cox model that included OR as a time-varying covariate and adjusted for age, visceral disease, and number of previous therapies. Results: Twenty-nine patients had confirmed OR; 20 by study week 7 and 7 more between study weeks 7 and 13. Survival probabilities 18 months after treatment initiation were 90% [95% confidence interval (CI) 65.6–97.4] in patients with OR at week 7 and 26.2% (95% CI 15.7–37.8) in patients without OR but who were alive at week 7. Median OS was not reached in patients with OR and was 8.8 months (95% CI 6.4–12.9) in patients without. Similar results were observed for the week 13 landmark. The adjusted Cox model showed OR was associated with a 95% risk reduction of death [hazard ratio 0.052 (95% CI 0.018–0.152)] compared with a nonresponse. Conclusions: Patients with OR by 7 or 13 weeks had significantly longer OS than patients without, confirming that early OR is an endpoint of major importance.

Original languageEnglish
Pages (from-to)609-618
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume68
Issue number4
DOIs
Publication statusPublished - Apr 2 2019

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Keywords

  • Avelumab
  • Endpoint validation
  • Merkel cell carcinoma
  • Objective response
  • Overall survival
  • PD-L1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

D’Angelo, S. P., Hunger, M., Brohl, A. S., Nghiem, P., Bhatia, S., Hamid, O., Mehnert, J. M., Terheyden, P., Shih, K. C., Brownell, I., Lebbé, C., Lewis, K. D., Linette, G. P., Milella, M., Schlichting, M., Hennessy, M. H., & Bharmal, M. (2019). Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma. Cancer Immunology, Immunotherapy, 68(4), 609-618. https://doi.org/10.1007/s00262-018-02295-4