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

Cancer Immunol Immunother. 2019 Apr;68(4):609-618. doi: 10.1007/s00262-018-02295-4. Epub 2019 Feb 5.


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.

Keywords: Avelumab; Endpoint validation; Merkel cell carcinoma; Objective response; Overall survival; PD-L1.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • Biomarkers, Tumor
  • Carcinoma, Merkel Cell / drug therapy*
  • Carcinoma, Merkel Cell / metabolism
  • Carcinoma, Merkel Cell / mortality*
  • Carcinoma, Merkel Cell / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Proportional Hazards Models
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • avelumab