A combination of durvalumab and standard first-line chemotherapy has shown promise for the management of untreated patients with advanced mesothelioma unsuitable for surgery.
The phase 2 single-arm Australian study, published in The Lancet Oncology, is the first clinical trial reporting on the combination of a checkpoint inhibitor and standard chemotherapy in malignant pleural mesothelioma.
The DREAM study comprised 54 patients from nine Australian hospitals treated intravenously with cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and durvalumab 1125 mg on the same day and repeated every 21 days for a maximum of six cycles.
Durvalumab was then continued as a single agent for another 12 cycles after completion of chemotherapy.
Six patients underwent a two-cycle safety run-in which found no dose-limiting toxicities.
The primary endpoint, progression-free survival at 6 months by mRECIST, was achieved by 31 patients (57%) which compares favourably to the expected 45% with standard chemotherapy.
“At a median follow-up of 28·2 months (IQR 26·5–30·2), median progression-free survival was 6·9 months (95% CI 5·5–9·0; figure 1A) by mRECIST and 7·0 months (5·7–9·0; table 2; appendix p 1) by iRECIST,” the study authors said.
There was no apparent association between tumour expression of PD-L1 and progression-free survival (6·3 months with PD-L1-negative tumours v 6·6 months for patients PD-L1-positive tumours).
The study found the confirmed objective tumour response was 48% according to both mRECIST and iRECIST.
The median overall survival was 18·4 months, with a 12-month overall survival of 65%) and a 24-month overall survival of 37%. Median time on study was 8.1 months with most patients discontinuing treatment due to disease progression (60%).