Avelumab in Previously Treated Advanced Unresectable Mesothelioma
In a phase Ib trial reported in JAMA Oncology, Hassan et al found that the anti–programmed cell death ligand 1 antibody avelumab produced durable responses and a high rate of disease control in some patients with advanced unresectable mesothelioma progressing after platinum and pemetrexed treatment.
Study Details
In the study, 53 patients from 25 sites in 3 countries enrolled between September 2014 and July 2015 were treated with avelumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Patients had a median age of 67 years (range = 32–84 years), 60% were male, and 38% had ≥ 3 prior lines of therapy (median = 2, range = 1–8).
Responses
Median follow-up was 24.8 months. Confirmed objective response occurred in 5 patients (9%), with complete response in 1 patient. The median duration of response was 15.2 months (95% confidence interval = 11.1 months–not estimable). Responses were observed in 3 (19%) of 16 patients with PD-L1–positive tumors and 2 (7%) of 27 with PD-L1–negative tumors using a cutoff for positivity of ≥ 5% expression. Overall, the disease control rate was 58%. Median progression-free survival was 4.1 months, with a 12-month rate of 17.4%. Median overall survival was 10.7 months, with a 12-month rate of 43.8%.
Adverse Events
Grade ≥ 3 treatment-related adverse events occurred in 5 patients (9%), consisting of pneumonitis, colitis, blood creatine phosphokinase increase, hypoalbuminemia, and type 1 diabetes mellitus. Treatment-related immune-mediated adverse events of any grade occurred in 12 patients (23%), including pneumonitis (3 patients, 6%), colitis (2 patients, 4%), hyperthyroidism (2 patients, 4%), and hypothyroidism (2 patients, 4%); adverse events were grade ≥ 3 in 3 patients (6%). Serious adverse events occurred in 22 patients (43%) and were considered treatment related in 5 patients. No treatment-related deaths were observed.
The investigators concluded, “Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma.”
Raffit Hassan, MD, of the Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Merck KGaA, and is part of an alliance between Merck KGaA and Pfizer, Inc. Additional research funding was provided by the National Cancer Institute. The study authors' full disclosures can be found at jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
