Avelumab Shows Positive Response, Safety Profile for Stage IV Merkel Cell Carcinoma

Data from a recent interim analysis of a clinical trial published in JAMA Oncology suggests that the administration of first-line PD-L1 inhibitor avelumab (Bavencio, Merck/Pfizer) has shown a manageable safety and efficacy profile in patients with stage IV metastatic Merkel Cell Carcinoma (mMCC).

First-line avelumab treatments, in general, were well tolerated with no treatment-related deaths or grade 4 adverse effects. About 70% of participants were reported to have at least 30% reductions in target lesions from their baselines, according to the study’s lead author Sandra P D’Angelo, MD, of the Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center in New York, NY.

The study’s primary endpoint was to have a durable response, defined as an objective response with a duration of at least 6 months (according to Response Evaluation Criteria in Solid Tumors version 1.1). Secondary endpoints included best overall response, duration of response, progression-free survival, safety, and tolerability.¹

According to the results, at the preplanned 3-month follow-up, the confirmed objective response rate was 62.1% with 14 of 18 responses (77.8%) ongoing at the time of analysis. In patients who responded, the estimated proportion with a duration response of at least 3 months was 93%. The duration response of patients at 6 months was 83%. The median time response for participants in the 3-month follow-up analysis was 6.1 weeks.

Over the course of the trial, 61.5% (24 patients) had ongoing treatment, and 38.5% (15 patients) discontinued treatment due to disease progression, adverse events or death (death was not treatment related).

The clinical trial sought to evaluate the efficacy and safety of first-line avelumab monotherapy treatments in patients with mMCC. Adults with stage IV mMCC who had not received previous systematic treatment for metastatic diseases and who did not have autoimmune conditions were eligible to participate. Patients who participated in the study were examined and evaluated every 6 weeks for tumor assessments, which were based on the Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee.

Among the data collected from each participant at each exam, the primary data included the confirmed objective response rate, the median time response, and the tumor status.

All 39 of the participants who qualified for and participated in the clinical trial (30 males and 9 females) ranged from 47 to 88 years of age and (a median age of 75 years). The follow-up had a median time of 5.1 months; however, in a preplanned analysis, there was a follow-up at 3 months in 29 participants. Each participant was administered 10 mg/kg of avelumab by 1-hour intravenous infusions every 2 weeks until a confirmation of disease progression, unacceptable toxic effects, or withdrawal occurred. While enrollment for the clinical trial is still ongoing, data was collected from April 15, 2016 to March 24, 2017.

Due to the clinical trial’s findings of high responses and efficacy rates with first-line avelumab therapy in patients with distant mMCC, the data only further supports avelumab as an efficient treatment for mMCC, according to the study authors. Biomarkers, such as PD-L1 expressions and viral statuses, will be investigated in future analyses first-line avelumab treatments.

The therapy was also being investigated as a treatment for patients with non-small cell lung cancer but fell short of its endpoints in the phase 3 JAVELIN Lung 200 trial in mid-February.²

mMCC is a rare and aggressive skin cancer that originates in skin cells as painless lumps before spreading to other regions of the body. UV light exposure and a weak immune system can contribute to the development of mMCC while other risk factors, such as fair skin and a male sex, can also contribute.

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Reference:

1. “Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma.” Journal of the American Medical Association, 22 Mar. 2018.
2. Jerusalem G, Chen FL, Spigel D, et al. JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti-PD-L1) as First-Line Treatment in Patients with Advanced NSCLC. Presented at: 17th World Lung Cancer Conference, the Annual Meeting of the International Association for the Study of Lung Cancer (IASLC); December 4-7, 2016; Vienna, Austria.