Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial
Abstract
Abstract SOLACE2 (ACTRN12618000686202) investigates whether 12-weeks of olaparib, or cyclophosphamide-olaparib priming, improves subsequent durvalumab-olaparib progression-free survival (PFS), and is superior to olaparib monotherapy without any priming, in platinum-sensitive recurrent ovarian cancer (n = 114). We also evaluate the utility of CUP-CC assay, an immune signature of C-C chemokine receptor type 4 up-regulation, chemokines, and cytokines. Priming with olaparib, or cyclophosphamide-olaparib, followed by durvalumab-olaparib, are both associated with longer PFS compared to olaparib monotherapy, but do not reach the pre-specified primary endpoint of 36-week trial threshold (PFS36). PFS36 rates are 47.4% (95% CI, 31.0-62.1; olaparib priming then olaparib-durvalumab), 48.7% (32.5-63.2; olaparib-cyclophosphamide then olaparib-durvalumab) and 35.1% (20.4-50.3; olaparib monotherapy). PFS is significantly longer for the homologous recombination deficient (N = 71) as compared to the proficient (HRP) (N = 29) subgroups (Hazard Ratio (HR) 0.55, 0.35-0.87). CUP-CC+ subgroup (N = 58) has a significantly longer PFS (HR 0.31, 0.19-0.49) than CUP-CC- (N = 46). Future studies should investigate whether CUP-CC has the potential to personalize poly (ADP-ribose) polymerase inhibitor therapies for patients who are BRCA wild-type, including HRP patients.
Article Details
Authors (35)
Chee Khoon Lee
Department of Medical Oncology, Cancer Care Centre, St. George Hospital, Kogarah, NSW, Australia
Apriliana E. R. Kartikasari
Nirashaa T. Bound
Katherine E. Francis
Kristy Shield-Artin
Justin Bedo
Ksenija Nesic
Katrina Diamante
Rachel L. O’Connell
Mutsa Madondo
Momodou Cox
Claire Davies
Cyril Deceneux
Georgia Goodchild
Andrew Jarratt
Emily Cassar
Hina Amer
U. G. Imalki U. Kariyawasam
Yeh Chen Lee
Janine Lombard
Sally Baron-Hay
Yoland Antill
Catherine Shannon
Sudarshan Selva-Nayagam
Philip Beale
Danka Zebic
Sandy Simon
Anneliese Linaker
Michael A. Quinn
Anthony T. Papenfuss
Matthew J. Wakefield
Cassandra J. Vandenberg
Michael Friedlander
Clare L. Scott
Magdalena Plebanski