A recent systematic review and meta-analysis published in the Taiwanese Journal of Obstetrics & Gynecology on May 6, 2024 examined the efficacy and safety of rucaparib in patients with recurrent high-grade ovarian carcinoma. The study, conducted by researchers from the Atma Jaya Catholic University of Indonesia and Padjadjaran University, aimed to provide a comprehensive overview of rucaparib's therapeutic potential in this challenging clinical context.
This meta-analysis included seven studies, comprising six randomized controlled trials and one retrospective study, with a total of 1,038 patients from various countries and medical centers. The researchers conducted a systematic search of studies reporting on rucaparib's efficacy and safety up to September 2023, utilizing reputable databases such as PubMed, ScienceDirect, Cochrane Library, EBSCOHost, ProQuest, and gray literature sources.
The study population consisted of patients aged 18 years or older with histologically confirmed diagnoses of high-grade ovarian, fallopian tube, or primary peritoneal cancer. Eligible participants had radiologically confirmed relapsed or recurrent disease prior to enrollment. The intervention group received rucaparib, while the control group received other treatments or placebo. Essential data extracted from the studies included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) based on RECIST v1.1 criteria, and adverse events (AEs).
The demographic data revealed that participants ranged in age from 35 to 91 years. A significant subset of the study population (n=574) carried BRCA mutations. The typical treatment regimen consisted of 600 mg of rucaparib administered orally twice daily over 21 or 28-day cycles.
The meta-analysis yielded several key findings regarding rucaparib's efficacy. The pooled objective response rate (ORR) was 0.331 (95% CI, 0.221-0.449), with significant heterogeneity observed among the studies (I2=92.4%). Subgroup analysis revealed that patients with BRCA mutations demonstrated superior outcomes. The complete response rate was 62.4% (95% CI, 0.361-0.951), while the partial response rate was 30.7% (95% CI, 0.161-0.475).
Progression-free survival (PFS) data from six studies (n=1,166) showed a range of 1.8 to 22.9 months. Notably, two studies reported that the intention-to-treat population receiving rucaparib treatment had higher PFS compared to the control group. For instance, one study recorded a PFS of 10.8 months for rucaparib versus 5.4 months for the control group (HR 0.36, 95% CI 0.30-0.45).
Overall survival (OS) data, available from two studies with 276 participants, ranged from 5.5 to 28.6 months. Subgroup analysis based on BRCA status demonstrated that patients with BRCA mutations had a superior OS of 22.7 months compared to 14.7 months for BRCA wild-type/LOH-high patients and 13.3 months for BRCA wild-type/LOH-low patients.
Regarding safety, the analysis revealed that 98.7% (95% CI, 96.2%-99.9%) of patients experienced treatment-emergent adverse events (TEAEs). Of these, 61% (95% CI, 55.0%-68.8%) were grade 3 or higher. The most common TEAEs included nausea (69.1%), fatigue (67.0%), vomiting (37.4%), and constipation (32.3%). Hematological adverse events were also notable, with anemia occurring in 48.2% of patients, thrombocytopenia in 25.5%, and neutropenia in 17.8%. Hepatotoxicity, characterized by elevated AST/ALT levels, was observed in 37.5% of patients, while nephrotoxicity, indicated by increased serum creatinine levels, occurred in 19.9% of patients.
The study had several limitations. The level of evidence was suboptimal due to the inclusion of only two phase III clinical trials, which were the only studies offering a comparator to rucaparib. Additionally, only one-third of the incorporated studies presented data on overall survival. There was also variation in therapy duration across the studies, and significant heterogeneity was observed in both efficacy and safety outcomes.
Despite these limitations, the authors concluded that rucaparib represents a prominent therapeutic choice for patients with relapsed high-grade ovarian carcinoma, demonstrating a commendable safety record. The consolidated objective response rate and marked complete response rate, especially in the BRCA-mutated cohort, support its therapeutic value. However, the researchers emphasized the need for meticulous surveillance, judicious clinical measures, and dose modulations to amplify therapeutic gains and attenuate potential risks.
The potential clinical impact of this study is significant. It provides comprehensive evidence supporting the use of rucaparib in recurrent ovarian cancer, particularly for patients with BRCA mutations. The findings underscore the importance of genetic testing to identify patients who may benefit most from this targeted therapy. Furthermore, the detailed safety profile presented in this meta-analysis can guide clinicians in managing and mitigating adverse events, potentially improving patient outcomes and quality of life.
Moving forward, the authors suggest that future research should focus on conducting expansive, multi-center randomized studies to further validate these conclusions. Additionally, determining the optimal duration and commencement of treatment, as well as exploring potential synergies with other therapeutic modalities, could enhance the clinical utility of rucaparib in the management of recurrent ovarian cancer.
In conclusion, this meta-analysis provides valuable insights into the efficacy and safety of rucaparib in recurrent high-grade ovarian carcinoma. While the results are promising, particularly for patients with BRCA mutations, the study also highlights the need for careful patient monitoring and management of adverse events. As the landscape of ovarian cancer treatment continues to evolve, this research contributes to the growing body of evidence supporting the use of PARP inhibitors in targeted therapy approaches.
References
Adrianto N, Mangkuliguna G, Tandiono EJ, Sibarani CNR. Efficacy and safety of rucaparib in patients with recurrent high-grade ovarian carcinoma: A systematic review and meta-analysis. Taiwan J Obstet Gynecol. 2024;63(5):601-609. doi:10.1016/j.tjog.2024.05.020
