As reported in The Lancet Oncology by Nowak et al, the Australian phase II DREAM trial showed activity with the triplet of durvalumab plus cisplatin/pemetrexed in previously untreated patients with advanced malignant mesothelioma.

Study Details

In the multicenter trial, 54 evaluable patients with measurable disease were enrolled between December 2016 and September 2017. All histologic subtypes were eligible (epithelioid in 83%).

Patients received cisplatin at 75 mg/m², pemetrexed at 500 mg/m², and durvalumab at 1,125 mg on day 1 of 3-week cycles for a maximum of six cycles. Change to carboplatin at AUC 5 from cisplatin was permitted. Durvalumab was continued for a maximum of 12 months. The primary endpoint was progression-free survival at 6 months on modified Response Evaluation Criteria in Solid Tumors (mRECIST) for malignant pleural mesothelioma in the intention-to-treat population.

Progression-Free Survival

Median follow up was 28.2 months. Progression-free survival at 6 months was achieved in 31 (57%) of 54 patients. Median progression-free survival was 6.9 months on mRECIST and 7.0 months on modified RECIST for immunotherapy (iRECIST). Median overall survival was 18.4 months, with 1- and 2-year rates of 65% and 37%.

Among 51 patients with available tumor tissue, 27 had PD-L1–positive tumors (tumor proportion score ≥ 1%) and 24 had PD-L1–negative tumors. No apparent association was observed between PD-L1 status and progression-free survival, with median progression-free survival of 6.3 months in patients with PD-L1–negative tumors and 6.6 months in individuals with PD-L1–positive tumors.

Objective response was observed in 26 patients (48%) according to mRECIST and in 26 patients (48%) according to iRECIST. All responses were partial responses. Responses were observed in all histologic subtypes, including biphasic and desmoplastic.

Adverse Events

The most common grade 3 or 4 adverse events were neutropenia (13%), nausea (11%), and anemia (7%). Serious adverse events occurred in 54% of patients; five patients (9%) had serious adverse events considered possibly related to durvalumab, consisting of renal impairment in two, adrenal insufficiency in one, infusion reaction in one, and visual blurring in one. Immune-related adverse events occurred in 12 patients (22%), including hypothyroidism in 5 (9%), increased amylase or lipase in 2 (4%), and pneumonitis in 2 (4%).

Treatment-related adverse events led to discontinuation of treatment in two patients, one due to increased creatinine (attributed to durvalumab) and one due to cardiac chest pain. Death occurred in five patients during study treatment, with none of the deaths considered related to treatment.

The investigators concluded, “The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomized phase III trial.”

Anna K. Nowak, PhD, of the Medical School, University of Western Australia, Perth, is the corresponding author for The Lancet Oncology article.  

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.