Anti-PD-L1 agent shows promise in malignant mesothelioma
medwireNews: The programmed cell death ligand 1 (PD-L1) inhibitor avelumab has clinical activity and a manageable toxicity profile in patients with previously treated, unresectable malignant mesothelioma, according to phase Ib trial results.
Among 53 participants of the mesothelioma cohort from the JAVELIN Solid Tumor trial, all of whom had unresectable disease that had progressed after platinum and pemetrexed treatment, administration of avelumab 10 mg/kg every 2 weeks led to an objective response lasting for a median of 15.2 months in 9%. One patient had a complete response, while the remaining four had a partial response.
Additionally, 26 patients had stable disease, which gave a disease control rate of 58%, Raffit Hassan (National Cancer Institute, Bethesda, Maryland, USA) and co-investigators report in JAMA Oncology.
Over a median follow-up of 24.8 months, the median progression-free survival (PFS) and overall survival (OS) durations were 4.1 and 10.7 months, respectively, and the corresponding 12-month rates were 17.4% and 43.8%.
“These findings are encouraging in a disease setting where treatment options are limited,” say the study authors.
When patients were stratified by PD-L1 expression, the 16 patients with PD-L1 positivity (≥5% of tumor cells) had a numerically higher objective response rate (19 vs 7%), as well as longer median PFS (5.3 vs 1.7 months) and OS (20.2 vs 10.2 months), than the 27 who were negative for PD-L1, but the between-group differences were not significant.
Avelumab has an “acceptable safety profile,” say Hassan et al, with treatment-related adverse events (AEs) of grade 3 or worse occurring in 9% of participants, while 6% experienced an immune-related AE of this severity that was attributed to treatment.
Nineteen percent of patients discontinued avelumab due to a treatment-related AE, most commonly infusion-related reactions, but there were no treatment-related deaths.
The team writes: “Although the study and its findings should be interpreted in context as a small phase 1b cohort, the level of long-term disease control, the duration of OS, and the safety profile suggest that avelumab could be a potential new therapeutic option for patients with mesothelioma.
“Further studies of avelumab or other anti–PD-1 or anti–PD-L1 antibodies in this disease, including combinations with other agents, are warranted.”
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