Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

DREAM - A phase 2 trial of DuRvalumab with first line chEmotherApy in Mesothelioma: Final result (#102)

Peey-Sei Kok 1 , Martin Stockler 1 , Willem Lesterhuis 2 , Brett Hughes 3 , Chris Brown 1 , Steven Chuan-Hao Kao 4 , Deme Karikios 5 , Thomas John 6 , Nick Pavlakis 7 , Ken O'Byrne 8 , Sonia Yip 1 , Wei-Sen Lam 9 , Karen Briscoe 10 , Chris Karapetis 11 , Anna Nowak 12
  1. NHMRC Clinical Trials Centre, Camperdown, NSW, Australia
  2. National Centre for Asbestos Related Diseases, University of Western Australia, Nedlands, WA, Australia
  3. The Prince Charles Hospital, Cancer Care Services, Brisbane, Qld, Australia
  4. Chris O'Brien Lifehouse, Sydney, Australia
  5. Nepean Hospital, Kingswood, NSW, Australia
  6. Olivia Newtown-John Cancer Research Institute, Heidelberg, VIC, Australia
  7. Northern Cancer Institute, University of Sydney , Sydney, NSW, Australia
  8. Princess Alexandra Hospital and Queensland University of Technology, Brisbane, Qld, Australia
  9. Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  10. Mid North Coast Cancer Institute, Coffs Harbour Health Campus, Coffs Harbour, NSW, Australia
  11. Flinders Medical Centre and Flinders University, Bedford Park, South Australia, Australia
  12. School of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Crawley, WA, Australia

Australia has the second highest incidence and death rate from malignant pleural mesothelioma (MPM) worldwide, after the United Kingdom. DREAM is an open-label, single arm, multi-centre, phase II trial designed to determine the activity, safety and tolerability of durvalumab combined with first-line chemotherapy in MPM. ACTRN12616001170415. Key eligibility criteria included all histological subtypes of MPM planned for first-line cisplatin and pemetrexed, unsuitability for radical surgery, no prior radiotherapy to measurement sites, and ECOG performance status of 0-1. Response was assessed using the mRECIST (modified Response Evaluation Criteria in Solid Tumors for MPM). Patients received durvalumab (1125mg), cisplatin (75mg/m2) and pemetrexed (500mg/m2) 3-weekly for a maximum of 6 cycles, followed by durvalumab alone (1125 mg 3-weekly) up to 12 months or until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 6 months (PFS6). Between Dec 2016 and Sep 2017, 54 patients were recruited. The median age was 68 (42-82) with 82% male and 60% ECOG 0. Forty-five patients (82%) had epithelioid subtype MPM. 31/54 (57%) of patients met primary endpoint of PFS6 with a median PFS of 6.8 months (95% CI: 5.4-9.0), at a median follow up time of 12 months, successfully rejecting the null hypothesis. The objective response rate (ORR) was 48% using mRECIST and 50% using iRECIST. The median duration of response was 6.5 months. 36 patients experienced grade 3-5 adverse events. Of four deaths on study, none were considered related to durvalumab treatment. Seventeen patients had irAEs of any grade, including 8 with G3-5 irAEs. Overall survival is maturing and will be presented at the meeting. Combination durvalumab with first-line chemotherapy for unresectable MPM showed promising activity and acceptable tolerability, with expected immune toxicities. Further evaluation to compare with chemotherapy alone will be generated through a phase 3 randomised controlled trial.