7/12/2023 0 Comments Endnote rutgers6 - 8 Trials involving anti–PD-1/PD-L1 antibodies have shown clinical activity and durable responses in patients with advanced MCC. Programmed cell death ligand 1 (PD-L1) is expressed on MCC tumor cells and in the MCC tumor microenvironment, indicating a potential role for immune checkpoint inhibitors such as anti–PD-L1 and anti–programmed cell death 1 (PD-1) antibodies. 3 In retrospective studies of first-line chemotherapy in patients with mMCC, median progression-free survival (PFS) was 3.1 to 4.6 months, 4, 5 highlighting the need for improved treatment options. 1, 2 Despite MCC being a chemosensitive disease, durable responses are rare. 1 Merkel cell carcinoma (MCC) is associated with Merkel cell polyomavirus infection, UV light exposure, and advanced age additional risk factors include fair skin and male sex. Metastatic Merkel cell carcinoma (mMCC) is a rare, aggressive skin cancer with poor survival. Trial Registration Identifier: NCT02155647 These data further support avelumab’s approval in the United States and European Union and use as a standard-of-care treatment for mMCC. First-line avelumab treatment was generally well tolerated, and no treatment-related deaths or grade 4 adverse events occurred.Ĭonclusions and Relevance High rates of response to first-line avelumab therapy in patients with distant mMCC build on previously reported antitumor activity after second-line or later treatment, and maturing progression-free survival data suggest that responses are durable. In responding patients, the estimated proportion with duration of response of at least 3 months was 93% (95% CI, 61%-99%) duration of response of at least 6 months, 83% (95% CI, 46%-96%). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing at the time of analysis. Results As of March 24, 2017, 39 patients were enrolled (30 men and 9 women median age, 75 years ), with a median follow-up of 5.1 months (range, 0.3-11.3 months). Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Main Outcomes and Measures Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. Interventions Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Objective To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC.ĭesign, Setting, and Participants JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti–programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). Importance Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease.
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