Raffit Hassan, MD
The immune checkpoint inhibitor avelumab demonstrated clinical activity in patients with advanced or unresectable mesothelioma, data from a multicohort, dose-expansion trial showed.
Five of 53 patients had partial responses, and 25 others had stable disease, resulting in a disease control rate of 56.6%. Evaluation of response by a tumor’s PD-L1 status showed an overall response rate of 14.3% for patients with tumors exhibiting ≥5% cell staining for PD-L1, versus 8.1% for patients with PD-L1–negative tumors, as reported at the 2016 ASCO Annual Meeting.
“Avelumab monotherapy had antitumor activity in patients with chemotherapy-refractory PD-L1–positive and PD-L1–negative tumors,” said Raffit Hassan, MD, co-chief of the Gastrointestinal and Thoracic Oncology Branch of the National Cancer Institute. “Ongoing follow-up will further characterize the durability of the clinical benefit.”
“This dataset is the largest study to date of patients with mesothelioma treated with an anti–PD-1 or anti–PD-L1 antibody,” he added.
The findings came from an analysis of patients included in a phase I clinical evaluation of avelumab at various doses and in various types of advanced malignancies. The mesothelioma cohort involved patients who had progressive disease during or after treatment with platinum/pemetrexed chemotherapy.
Patients were unselected for tumor PD-L1 expression, and they had good performance status and a life expectancy of at least 3 months. No prior exposure to T-cell targeting or anti-PD-1/PD-L1 antibodies were allowed, nor was any anticancer therapy within the previous 28 days. Patients on immunosuppressive therapy underwent drug tapering to discontinuation before starting avelumab.
Treatment consisted of avelumab 10 mg/kg every 2 weeks, continued until disease progression or development of unacceptable toxicity. Outcomes of interest included best overall response, safety/tolerability, progression-free survival, and PD-L1 expression in tumor tissue.
The patients were a median age of 66 years, the median time since mesothelioma diagnosis was 1.8 years, and 25% to 30% of the patients had received 1-3 prior therapies. More than 80% of the patients had tumors with epithelial histology.
The median treatment duration was 12 weeks, and all patients had a minimum follow-up of 11.3 weeks. Hassan said 14 patients remained on treatment.
Analysis of tumor expression in 39 evaluable patients showed PD-L1 staining of ≥1% of tumor cells in 20 patients, ≥5% in 14 patients, ³25% in 7 patients, and ≥10% of tumor-infiltrating immune cells in 6 patients.
The overall response rate was 9.4%, and no patient had a complete response. Four of the 5 partial responses were ongoing at last data analysis. The patients had a median PFS of 17.1 weeks, and 38.4% of the patients remained alive without progression at 24 weeks.
Among patients with at least 1% tumor cell staining for PD-L1 (n =14), median PFS was 17.1 weeks, and 39.2% of patients were alive without progression at 24 weeks. Patients with PD-L1 negative tumors (n = 25) had a median PFS of 7.4 weeks and a 24-week PFS of 40.7%.
Avelumab was well tolerated. The most common treatment-related adverse events were infusion-related reaction (n = 20), fatigue (8), chills (8) pyrexia (6), decreased appetite (5), asthenia (4), and pruritus (4). Four patients had grade ³3 adverse events: 1 case each of decreased gamma-glutamyl transferase, decreased lymphocyte count, colitis, and increased blood CPK. Six patients discontinued treatment following a treatment-related adverse event.
Potential immune-mediated adverse events included 2 cases each of hyper- and hypothyroidism and 1 case each of increased levels of antinuclear antibody, autoimmune thyroiditis, colitis, and pneumonia.
No treatment-related deaths occurred.
Hassan R, Thomas A, Patel MR, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced unresectable mesothelioma from the JAVELIN solid tumor phase Ib trial: safety, clinical activity, and PD-L1 expression. J Clin Oncol. 2016;34(suppl; abstr 8503).<<< View more from the 2016 ASCO Annual Meeting