Chee Khoon Lee, Apriliana E. R. Kartikasari, Nirashaa Bound, Katherine E. Francis, Kristy Shield‐Artin, Justin Bedő, Ksenija Nesic, Katrina Diamante, Rachel O’Connell, Mutsa Madondo, Momodou Cox, Claire M. Davies, Cyril Deceneux, Georgia Goodchild, Andrew Jarratt, Emily Cassar, Hina Amer, U. G. I. U. Kariyawasam, Yeh Chen Lee, Janine Lombard, Sally Baron‐Hay, Yoland Antill, Catherine Shannon, Sudarshan Selva‐Nayagam, Philip Beale, Danka Sinikovic Zebic, Sandy Simon, Anneliese Linaker, Michael Quinn, Anthony T. Papenfuss, Matthew J. Wakefield, Cassandra J. Vandenberg, Michael Friedländer, Clare L. Scott, Magdalena Plebanski
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.