Patients with treatment-naïve and unresectable malignant pleural mesothelioma may respond to treatment with durvalumab given alongside cisplatin and pemetrexed, according to phase 2 results presented at the Virtual ASCO Annual Meeting, held 29-31 May, 2020 .
Presented by Prof. Patrick Forde (Johns Hopkins University, USA) , the phase 2 PrE0505 study enrolled 55 patients with newly diagnosed unresectable malignant pleural mesothelioma. The trial had a single arm, namely chemotherapy with durvulumab 1120 mg, cisplatin 75 mg/m2, and pemetrexed 500 mg/m2 every 3 weeks, for a maximum of 6 cycles, followed by a year of maintenance durvalumab alone. The comparator was a pemetrexed–cisplatin historical control.
Histological characterization revealed that 75% of patients had epithelioid histology, while 13% had sarcomatoid, 11% biphasic, and/or 2% desmoplastic histologies.
The pre-specified criteria for clinically meaningful benefit was set at 19.0 months, corresponding to a 58% improved median overall survival (OS) associated with the historical control group (12.0 months). The primary endpoint was met; the median OS in this trial with the addition of durvulumab was 20.4 months. The 6-, 12-, and 24-month OS rates were 87.2%, 70.4%, and 44.2%, respectively, while corresponding progression-free survival (PFS) rates were 69.1%, 16.4%, and 10.9%. The median PFS was 6.7 months.
At the data cut-off on 24 April 2020, 56.4% of patients had a partial response, 40.0% had stable disease, and 1.8% had progressive disease.
Durvalumab combined with platinum-based chemotherapy was well tolerated, with no new safety signals. Grade 3 or higher adverse events occurred in 36 patients, probably immunotherapy related. Grade 1-2 adverse events were hypothyroidism (n=7), rash (n=5), pruritus (n=3), aspartate aminotransferase AST elevation (n=3), hyperthyroidism (n=3), dermatitis (n=2), neuropathy (n=2), alanine aminotransferase elevation (n=1), lipase increase (n=1), and pneumonitis (n=1).
Tumor mutational burden (TMB) and PD-L1 expression were also examined. Although not significant, median OS among patients was numerically higher in patients with a TMB of 24 or higher, at (27.9 months versus 14.2 months for those with TMB <24).
- Forde P, et al. PrE0505: Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (MPM)—A PrECOG LLC study. ASCO Virtual Meeting, 29-31 May 2020, Abstract 9003.