PT - JOURNAL ARTICLE AU - Kaufman, Howard L. AU - Russell, Jeffery S. AU - Hamid, Omid AU - Bhatia, Shailender AU - Terheyden, Patrick AU - D’Angelo, Sandra P. AU - Shih, Kent C. AU - Lebbé, Céleste AU - Milella, Michele AU - Brownell, Isaac AU - Lewis, Karl D. AU - Lorch, Jochen H. AU - von Heydebreck, Anja AU - Hennessy, Meliessa AU - Nghiem, Paul TI - Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial AID - 10.1186/s40425-017-0310-x DP - 2018 Dec 01 TA - Journal for ImmunoTherapy of Cancer PG - 7 VI - 6 IP - 1 4099 - http://jitc.bmj.com/content/6/1/7.short 4100 - http://jitc.bmj.com/content/6/1/7.full SO - J Immunother Cancer2018 Dec 01; 6 AB - Background Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab—a human anti–programmed death-ligand 1 (PD-L1) monoclonal antibody—showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease.Patients and methods Patients received avelumab 10 mg/kg by 1-h intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was best overall response. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).Results Patients (N = 88) were followed for a minimum of 12 months. The confirmed objective response rate was 33.0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of responses lasted ≥1 year, and 72.4% of responses were ongoing at data cutoff. Responses were durable, with the median DOR not yet reached (95% CI, 18.0 months-not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI, 21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95% CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of response in patients receiving fewer prior lines of systemic therapy, with a lower baseline disease burden, and with PD-L1–positive tumors; however, durable responses occurred irrespective of baseline factors, including tumor Merkel cell polyomavirus status.Conclusions With longer follow-up, avelumab continues to show durable responses and promising survival outcomes in patients with distant mMCC whose disease had progressed after chemotherapy.Trial registration Clinicaltrials.gov identifier: NCT02155647.Abbreviations:2 LSecond-line2 L +Second-line or laterCIConfidence intervalCRComplete responseDORDuration of responseDRRDurable response rateECOGEastern Cooperative Oncology GroupFDAFood and Drug AdministrationHIVHuman immunodeficiency virusMCPyVMerkel cell polyomavirusMMCCMetastatic Merkel cell carcinomaNENot estimableNRNot yet reachedORRObjective response rateOSOverall survivalPDProgressive diseasePD-1Programmed death-1PD-L1Programmed death-ligand 1PFSProgression-free survivalPRPartial responseRECISTResponse Evaluation Criteria In Solid TumorsSLDSum of target lesion diametersUVUltraviolet