A three-agent neoadjuvant regimen that combines a PD-L1 inhibitor with chemotherapy appears feasible for patients with malignant pleural mesothelioma, according to an ongoing phase I trial. The findings [ about neoadjuvant therapy ] were presented at the International Association for the Study of Lung Cancer virtual World Conference on Lung Cancer, which took place from September 8 to 14.
Malignant pleural mesothelioma is an orphan disease with limited treatment options. Median overall survival ranges from 17 to 25 months for patients with curable disease who undergo neoadjuvant chemotherapy, surgical resection, and adjuvant radiation. “It is an immunogenic disease, and the PD-L1 target has been identified in mesothelioma tumor cells and [has been] associated as a negative prognostic biomarker,” said co-author Boris Sepesi, MD, of the MD Anderson Cancer Center in Houston, during a press briefing attended by Elsevier’s PracticeUpdate.
The researchers hypothesized that adding a PD-L1 inhibitor to neoadjuvant cisplatin-pemetrexed therapy, followed by maintenance immunotherapy after surgical resection and adjuvant radiation, will enhance T-cell activation against microscopic disease and potentially increase overall survival outcomes. To find out, they enrolled 28 patients with stage I to III malignant pleural mesothelioma who were chemotherapy naïve. Of these patients, 24 were white, 20 were male, and the median age was 68.1 years.
Overall, 21 patients completed all four cycles of neoadjuvant cisplatin-pemetrexed-atezolizumab therapy, and 25 completed at least two cycles. There were 18 patients who had stable disease or a partial response and were subsequently treated by surgical resection, with 16 of these patients going on to start maintenance atezolizumab. Seven patients did not undergo resection, due to disease progression (4 patients), toxicity (2 patients), or death due to sepsis (1 patient).
Grade 3 adverse events during neoadjuvant therapy included neutropenia in 3 patients, anemia in 2 patients, and 1 case each of diarrhea, febrile neutropenia, hyponatremia, nausea, and vomiting. During maintenance therapy, grade 3 hypotension occurred in 1 patient. There were no grade > 3 treatment-related adverse events during maintenance therapy. Three patients remain on the therapy.
“This trial highlights the challenging nature of neoadjuvant therapy trials in this patient population, because of the heterogeneity of the disease and how patients react, as well as the complex and difficult surgical therapy,” said Dr. Sepesi “However, I think this is a step forward in terms of treatment.”
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