First results of DREAM trial of frontline durvalumab for mesothelioma

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Published: 5 Jun 2018
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Prof Anna Nowak - The University of Western Australia, Perth, Australia

Dr Nowak speaks with ecancer at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting about the results from the DREAM trial comparing durvalumab as a first line treatment for mesothelioma patients compared to platinum-based chemotherapy.

She outlines the current patient cohort and treatment schedules for the study arms, and notes the impact of durvalumab on patients progression free survival at 6 months.

Dr Nowak also discusses the toxicity profile of frontline durvalumab, with 3 grade 3 events and 4 non-trial related deaths.


DREAM was a phase II trial of durvalumab and chemotherapy in malignant pleural mesothelioma. These were untreated patients, so first line, and the study was a phase II multi-centre study in Australia. We had ten sites open and we recruited 54 patients in 10 months, which was 8 months ahead of schedule.

This was a phase II clinical trial with a six patient safety lead-in. The patients received a combination of cisplatin and pemetrexed with durvalumab. All patients received cisplatin and pemetrexed for up to six cycles, as per standard therapy. This was given concurrently with durvalumab 1125mg flat dose given every three weeks also and that was to a maximum of twelve months of treatment. Patients who were intolerant to cisplatin or had cisplatin-related toxicities were allowed to cross over to carboplatin but that was a small number of patients.

The results that I’m presenting here at ASCO are from the first 31 patients. We just reached six months PFS just before the ASCO abstracts were due in December. The 54 patients have just reached their six months PFS about a month ago but I’m not presenting them at this meeting.

The patient population was as you would expect for patients with advanced malignant mesothelioma – they were a population who were not considered operable or for whom an operation was not considered appropriate. They were mostly older patients, male, and in the first 31 patients it was a predominantly epithelioid subtype, all but one patient and that one patient had biphasic disease.

In terms of results our progression free survival was 7.3 months with a six month PFS of 65% which met the criteria to move on to the second part of the study. The overall response rate was 58% and that was according to immune related RECIST with appropriate modifications for mesothelioma in terms of how the tumour was measured.

Looking at adverse events the adverse events appeared to be similar to chemotherapy or immunotherapy if they had been given separately, there was no indication in the safety run-in of six patients of any excessive toxicities. In terms of immune related toxicities there were three grade 3 immune related AEs and an additional two that required high dose corticosteroids. There were four deaths on study, none of these were related to study treatment as deemed by the investigator or the central review. One was a death from mesothelioma, one pulmonary embolism, one pneumonia and one cardiac arrest so these were considered in keeping with either disease progression or unfortunately the expected adverse events that can occur with mesothelioma. It is a small number on the study, admittedly.

And in terms of the future prospects for this information going forwards? Are we looking forward to a future evaluation or incorporating this into future trial design?

We are excited by these results, they’re really very promising for mesothelioma. Assuming that the full 54 patients carry through with very similar results we’re very keen to take this through to a randomised phase III trial and to include patient reported outcome measures and more biomarker studies in that. We do have biomarker studies – tissue and peripheral blood, PPMC – collected for the DREAM trial but as yet these haven’t been analysed.  We’ll be looking for a signal as to what we’d best take forward into a phase III.