RT Journal Article
SR Electronic
T1 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
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 7
DO 10.1186/s40425-017-0310-x
VO 6
IS 1
A1 Kaufman, Howard L.
A1 Russell, Jeffery S.
A1 Hamid, Omid
A1 Bhatia, Shailender
A1 Terheyden, Patrick
A1 D’Angelo, Sandra P.
A1 Shih, Kent C.
A1 Lebbé, Céleste
A1 Milella, Michele
A1 Brownell, Isaac
A1 Lewis, Karl D.
A1 Lorch, Jochen H.
A1 von Heydebreck, Anja
A1 Hennessy, Meliessa
A1 Nghiem, Paul
YR 2018
UL http://jitc.bmj.com/content/6/1/7.abstract
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