Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial

Lee, CK; Kartikasari, AER; Bound, NT; Francis, KE; Shield-Artin, K; Bedo, J; Nesic, K; Diamante, K; O&#39;Connell, RL; Madondo, M; Cox, M; Davies, C; Deceneux, C; Goodchild, G; Jarratt, A; Cassar, E; Amer, H; Kariyawasam, Ugiu; Lee, YC; Lombard, J; Baron-Hay, S; Antill, Y; Shannon, C; Selva-Nayagam, S; Beale, P; Zebic, D; Simon, S; Linaker, A; Quinn, MA; Papenfuss, AT; Wakefield, MJ; Vandenberg, CJ; Friedlander, M; Scott, CL; Plebanski, M

Author(s): Lee, CK; Kartikasari, AER; Bound, NT; Francis, KE; Shield-Artin, K; Bedo, J; Nesic, K; Diamante, K; O'Connell, RL; Madondo, M; Cox, M; Davies, C; Deceneux, C; Goodchild, G; Jarratt, A; Cassar, E; Amer, H; Kariyawasam, Ugiu; Lee, YC; Lombard, J; Baron-Hay, S; Antill, Y; Shannon, C; Selva-Nayagam, S; Beale, P; Zebic, D; Simon, S; Linaker, A; Quinn, MA; Papenfuss, AT; Wakefield, MJ; Vandenberg, CJ; Friedlander, M; Scott, CL; Plebanski, M;
Details: Publication Year 2025-11-05,Volume 16,Issue #1,Page 9756
Journal Title: Nature Communications
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.
Publisher: Springer Nature
Keywords: Humans; Female; *Phthalazines/administration & dosage/therapeutic use; *Ovarian Neoplasms/drug therapy/blood/genetics/mortality; *Piperazines/administration & dosage/therapeutic use; *Cyclophosphamide/administration & dosage/therapeutic use; Middle Aged; *Antibodies, Monoclonal/administration & dosage/therapeutic use; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Aged; Progression-Free Survival; Prognosis; Adult
Research Division(s): Cancer Biology and Stem Cells; Bioinformatics and Computational Biology
PubMed ID: 41193417
Publisher's Version: https://doi.org/10.1038/s41467-025-64130-6
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-025-64130-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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