TY - JOUR
T1 - Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up
T2 - JAVELIN Merkel 200, a phase 2 clinical trial
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
N1 - Funding Information:
This trial was sponsored by Merck KGaA, Darmstadt, Germany, and is part of an alliance between Merck KGaA, Darmstadt, Germany, and Pfizer, Inc., New York, NY, USA. Medical writing support was provided by ClinicalThinking, Inc., Hamilton, NJ, USA, and funded by Merck KGaA, Darmstadt, Germany, and Pfizer, Inc., New York, NY, USA.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/1/19
Y1 - 2018/1/19
N2 - 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.
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.
KW - Avelumab
KW - Javelin
KW - Merkel cell carcinoma
KW - Pd-L1
UR - http://www.scopus.com/inward/record.url?scp=85040729219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040729219&partnerID=8YFLogxK
U2 - 10.1186/s40425-017-0310-x
DO - 10.1186/s40425-017-0310-x
M3 - Article
C2 - 29347993
AN - SCOPUS:85040729219
SN - 2051-1426
VL - 6
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
M1 - 7
ER -
