Maintenance Therapy in Advanced Ovarian Cancer: A Benefit of Continued PARP Inhibitor Treatment

Dr Premal Thaker, from Washington University School of Medicine, reports from the ASCO Direct Series, St. Louis 2022.


The ATHENA trial was a clinical trial that investigated, in part, the use of a class of drugs called a PARP inhibitor, specifically, rucaparib, as a maintenance therapy for patients with ovarian cancer, which has one of the poorest prognoses of all gynecologic malignancies. There is evidence that patients with ovarian cancer having a mutation in the BRCA gene are candidates for maintenance therapy with a PARP inhibitor, although the relative benefit of continued, or so-called maintenance therapy, for these patients is not fully resolved. Recently reported at the ASCO 2022 meeting was the monotherapy arm of the ATHENA trial (ATHENA-MONO), which enrolled newly diagnosed patients with advanced (Stage III or IV) ovarian, fallopian tube, or primary peritoneal cancer who had completed their initial chemotherapy and surgery and had a complete or partial response, and who had not received a prior maintenance therapy. Notably, as compared to other trials in this area, about one fifth of patients in the trial were of Asian ethnicity, and about one quarter had more advanced (Stage IV) disease. About one quarter of patients in the trial also had some residual disease following chemotherapy for their cancer. Overall, at the present time, about one quarter of the patients in this trial have been able to tolerate the therapy and complete their treatment over a two-year trial period. Results of this trial showed, for patients in the HRD, or homologous recombination deficient population, about a 17-month increase in survival free of cancer progression for patients on rucaparib, relative to those taking the placebo. This was also true, to a lesser extent, for all the patients enrolled in the trial, or the ITT population, who had about an 11-month benefit on rucaparib relative to placebo. A higher number of patients on rucaparib compared to placebo also had a measurable reduction in their tumors relative to when they started treatment, and this was true in both the HRD and the ITT populations. The overall results indicate that patients on this therapy benefitted from the PARP maintenance therapy with rucaparib, as compared to those who received none. In terms of adverse events, in addition to the expected reduction in blood cell counts that are known to be associated with this type of drug, there was also some increase in liver function test abnormalities, or LFT elevations, with rucaparib, although these types of adverse events usually resolve within the first 3 months of treatment. Importantly, there was no adverse impact on measures of patients’ quality of life with maintenance rucaparib treatment, suggesting that the treatment caused no greater harm to the patients than placebo. Taken together, the results from ATHENA-MONO, in agreement with earlier results, indicated that patients with ovarian cancer did benefit from continued, or maintenance treatment with a PARP inhibitor, in this case, rucaparib, and this benefit was seen regardless of their HRD status. It is not yet known whether these patients will survive longer on rucaparib versus no treatment, and further follow up from the trial will be required to determine this.



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