Abstract 541P
Background
maintenance therapy with PARP-inhibitors (PARPi) may alter efficacy of further chemotherapy in advanced epithelial ovarian cancer (aEOC). We conducted a retrospective study to evaluate efficacy of various therapeutic agents in aEOC patients who progressed after maintenance olaparib therapy.
Methods
we extracted data for patients with BRCA-positive aEOC who progressed after maintenance olaparib therapy from a prospectively maintained institutional database for 2014-2022 years. Using Cox proportional hazards regression model we analyzed the impact of various platinum, non-platinum and antiangiogenic agents on progression-free survival (PFS) and overall survival (OS) of patients after subsequent anticancer therapy. Statistical analysis was done with R and RStudio software.
Results
we identified 146 patients who received maintenance olaparib in the specified timeline, of them 61 (41.7%) patients were treated with subsequent chemotherapy and had available outcomes data. Median duration of previous olaparib therapy was 11.5 mo., the drug was administered as maintenance therapy after median of 2 (1-7) lines of anticancer treatment. Median follow-up time post olaparib progression was 13.0 months. Median post progression PFS and OS were 7.2 mo. and 20.0 mo. Results of Cox-regression analysis of PFS and OS are summarized in Table below. Taxanes- and/or bevacizumab-containing therapy was associated with better outcomes compared to other therapeutic options. Administration of anthracyclines (PLD or doxorubicin) had a detrimental impact on PFS and OS. Table: 541P
| PFS | OS | |||
| Factor | HR (95% CI) | p | HR (95% CI) | p |
| >2 prior lines | .97 (.54-1.76) | .345 | .48 (.19-1.21) | .124 |
| Taxanes | 0.47 (.25-.86) | .014 | 0.26 (.07-.89) | .032 |
| Anthracyclines | 5.7 (2.48-13.12) | <.001* | 2.57 (1.02-6.51) | .045 |
| Gemcitabine | 1.28 (.64-2.56) | .469 | 1.15 (.37-3.53) | .797 |
| Pt-agents | 1.28 (.56-2.91) | .546 | .75 (.24-2.31) | .627 |
| Bevacizumab | .54 (0.29-0.98) | .043 | .46 (.17-1.20) | .114 |
*remained significant in multifactor analysis.
Conclusions
taxanes and bevacizumab are valuable therapeutic options for post-olaparib treatment. Anthracyclines may be associated with inferior outcomes in this setting. While optimal treatment for patients progressing after PARPi is unknown, our study provides some insights and hypothesis-generating data for further trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Rumyantsev: Financial Interests, Personal, Speaker’s Bureau: Biocad, AstraZeneca, Pfizer, MSD, Merck. A. Tyulyandina: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BIOCAD, Merck, Pfizer, Takeda, MSD. E. Glazkova: Financial Interests, Personal, Speaker’s Bureau: Biocad, AstraZeneca, R-Pharm, MSD, Pfizer. I. Pokataev: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Johnson & Johnson, MSD, Biocad, Sanofi, Roche, Eli Lilly. S. Tjulandin: Financial Interests, Personal, Ownership Interest: RosPharmTech; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Biocad, Eli Lilly, MSD.