Impact of PARP inhibitor maintenance therapy after initial treatment on the efficacy of subsequent therapy in ovarian cancer: a propensity score matching analysis

Introduction: progression of advanced epithelial ovarian cancer (EOC) on olaparib may diminish the efficacy of subsequent chemotherapy in recurrent disease setting. However, the impact of progression of EOC during maintenance therapy with olaparib after frontline therapy has not been well studied.

Materials and methods: this retrospective study enrolled patients of BRCA / HRD + FIGO stage III–IV EOC with confirmed progressive disease after frontline treatment treated since 2014 until 2022 who either received (arm A) or not (arm B) olaparib as maintenance therapy. To ensure the balance of the compared groups during the study propensity score matching analysis was conducted (cardinality method using MatchIT package in R) with 1:1 ratio of patients in trial arms. The groups were balanced according to the presence of residual tumor after initial treatment, the duration of platinum-free interval after the frontline therapy, secondary local therapy for recurrent disease, treatment with platinum drugs for relapse and subsequent bevacizumab. The primary endpoint of the study was progression-free survival (PFS).

Results: the initial population consisted of 259 patients, after the matching procedure 76 patients were enrolled in the study. The median age of patients was 48 years in the arm A and 50 years in the arm B (p = 0.989), 12 (32 %) had FIGO stage IV in both arms (p = 1.000), 25 (66 %) patients in both arms had platinum-free interval ≥ 12 months. With a median follow-up of 42.8 mo. (0.6–70.1 months) median PFS was 6.9 (95 % CI 6.2–10.6 months) and 12.2 (95 % CI 9. 6–21.3 months) in arm A and B, respectively (hazard ratio [HR] 2.89; 95 % CI 1.63–5.12; p < 0.001). Median overall survival was 23.2 months. and 68.2 mo., respectively (HR 4.15; 95 % CI 1.62–10.6).

Conclusion: efficacy of subsequent chemotherapy is apparently reduced following progression of BRCA / HRD + EOC on maintenance olaparib therapy in frontline setting. Further trials should assess optimal approaches for these patients.

1. Banerjee S., Moore K.N., Colombo N., et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2021;22(12):1721–1731. https://doi.org/10.1016/S1470-2045(21)00531-3

2. DiSilvestro P., Banerjee S., Colombo N., et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: The SOLO1/GOG 3004 trial. J Clin Oncol Off J Am Soc Clin Oncol 2023;41(3):609–617. https://doi.org/10.1200/JCO.22.01549

3. Wu X., Liu J., Wang J., et al. Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial. Nat Med 2024;30(6):1612–1621. https://doi.org/10.1038/s41591-024-03003-9

4. González-Martín A., Pothuri B., Vergote I., et al. Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer 2023;189:112908. https://doi.org/10.1016/j.ejca.2023.04.024

5. Monk B.J., Parkinson C., Lim M.C., et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45). J Clin Oncol 2022;40(34):3952–3964. https://doi.org/10.1200/JCO.22.01003

6. Dias M.P., Moser S.C., Ganesan S., Jonkers J. Understanding and overcoming resistance to PARP inhibitors in cancer therapy. Nat Rev Clin Oncol 2021;18(12):773–791. https://doi.org/10.1038/s41571-021-00532-x

7. Frenel J.S., Kim J.W., Aryal N., et al. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ ENGOT Ov-21 trial. Ann Oncol 2022;33(10):1021–1028. https://doi.org/10.1016/j.annonc.2022.06.011

8. Ho D.E., Imai K., King G., Stuart E.A. MatchIt: Nonparametric Preprocessing for Parametric Causal Inference. J Stat Softw 2011;42(8). https://doi.org/10.18637/jss.v042.i08

9. Fortin S.P., Johnston S.S., Schuemie M.J. Applied comparison of large-scale propensity score matching and cardinality matching for causal inference in observational research. BMC Med Res Methodol 2021;21(1):109. https://doi.org/10.1186/s12874-021-01282-1

10. Harter P., Mouret-Reynier M.A., Lorusso D., et al. Efficacy of subsequent therapies in patients (pts) with advanced ovarian cancer (AOC) in the phase III PAOLA-1/ENGOT-ov25 trial according to whether disease progression occurred during or after the end of olaparib (ola) maintenance. J Clin Oncol 2023;41(16_suppl):5550–5550. https://doi.org/10.1200/JCO.2023.41.16_suppl.5550.