Anna Nowak, MD, PhD, University of Western Australia, Perth, Australia, discusses results from the DREAMER trial which evaluated durvalumab plus chemotherapy versus chemotherapy alone in patients with advanced pleural mesothelioma. 

Results demonstrate that adding durvalumab to chemotherapy improves survival and response, reinforcing prior phase 2 findings and highlighting the ongoing potential of immunotherapy–chemotherapy combinations to improve treatment for patients with mesothelioma.

These results were presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.

Transcript: 

My name is Professor Anna Nowak, and I'm the principal investigator of the DREAMER clinical trial which is being presented today at ESMO. The DREAMER clinical trial was a collaboration between the Thoracic Oncology Group of Australia and PrECOG in the USA. 

DREAMER was initiated following the positive results of the DREAM and PrE0505 trials, both testing durvalumab plus chemotherapy versus chemotherapy alone. After the DREAMER trial was planned and just before initiation, CheckMate743 read out demonstrating improved survival for nivolumab plus ipilimumab versus chemotherapy in advanced pleural mesothelioma. The aim of the DREAMER clinical trial was to compare the overall survival of participants with advanced pleural mesothelioma treated with durvalumab plus chemotherapy versus chemotherapy alone, chemotherapy being cisplatin or carboplatin plus pemetrexed. The study was originally planned to recruit 480 participants; however, it was stopped early due to slow accrual because of the impact of treatment with ipilimumab and nivolumab becoming available in both Australia and the USA. The study recruited 214 patients, and I'm presenting results from 174 randomized to chemotherapy plus durvalumab versus chemotherapy alone. 

Because nivolumab plus ipilimumab came into standard care during the trial, protocol modifications were done due to slow recruitment and subsequent versions of the protocol incorporated physician’s choice between chemotherapy or ipilimumab plus nivolumab as the control arm. In results for the chemotherapy control arm versus durvalumab plus chemotherapy I'm talking about overall survival, progression-free survival, overall response rate, and toxicities. 

Of 174 participants, 114 were randomized to durvalumab plus chemotherapy and 62 to chemotherapy alone in a 2:1 randomization. Patient baseline characteristics were as expected for this population, with no specific imbalances between the arms. The median overall survival of chemotherapy plus durvalumab was 21 months and the median overall survival of chemotherapy alone was 18 months with an adjusted hazard ratio of 0.92 and a p-value of 0.9. Progression-free survival was 8 months for the intervention arm and 7 months for the control arm with an adjusted hazard ratio of 0.7 and a p-value of 0.2. Objective tumor response rate, as measured by the modified RECIST criteria, was 58% in the chemotherapy plus durvalumab arm versus 35% in the chemotherapy-alone arm. Toxicity was as expected for these combinations, although there were more grade 1 and 2 nausea and fatigue toxicities in the chemotherapy plus durvalumab arm and more hematological toxicities—anemia, neutropenia, and thrombocytopenia, grade 3 and 4—in the chemotherapy plus durvalumab arm. 

In conclusion, the DREAMER study confirmed the results of the DREAM and PrE0505 clinical trials. However, unfortunately, accrual was stopped early due to change in clinical practice. This means that the study question may never be fully answered, although the interesting overall tumor response rate suggests that examination of this combination in the neoadjuvant setting may be interesting. Other ongoing clinical trials may be able to answer the question of whether immunotherapy plus chemotherapy is superior to chemotherapy alone, particularly those using bispecific monoclonal antibodies against both PD-L1 and anti–CTLA-4. The slow accrual of the DREAMER trial also underscores the importance of timely activation of randomized phase 3 trials, which may be following on from successful phase 2 clinical trials.

Source: 

Nowak A, Forde PM, Brown C, et al. Primary results of DREAM3R: DuRvalumab (MEDI4736) with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma: A phase III randomised trial. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA104