Saitoh Aoki E, et al. J Gynecol Oncol. 2019 Jun;31:e55. https://doi.org/10.3802/jgo.2020.31.e55

PURPOSE: This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS: Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS: Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION: Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

Advancements in diagnostic and therapeutic standards have substantially enhanced the survival of patients with malignant tumors. Nevertheless, the quest for effective strategies to address resistant or recurrent advanced tumors remains a critical and unwavering objective. Bispecific antibodies (BsAbs) unleashed a new era of anti-tumor treatment by simultaneously binding to two distinct targets, thereby enhancing specificity, minimizing off-target toxicities, and synergistically modulating anti-tumor immunity and the tumor microenvironment. Compared with the combination of two monoclonal antibodies, BsAbs represent the physical integration of dual specificities, demonstrating superior binding efficacy, reducing the risk of drug resistance, and enabling unique biological functions such as bridging tumor cells and T cells to achieve precise cytotoxicity. However, limitations such as off-target toxicities, drug resistance and immune-related adverse effects require carefully evaluation and further optimization. Further studies are necessary to explore the potential of combining BsAbs with other anti-tumor strategies, balancing the efficacy and safety, optimizing the outpatient-based administration workflow. By tracking the research advancements of recently approved BsAbs and BsAb candidates in clinical trials, it is evident that BsAbs holds significant promise as a novel and transformative option for improving survival outcomes for patients.

Purpose: Fluzoparib (PARP inhibitor) showed promising anti-tumor activity for advanced ovarian cancer in a phase 1 study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer. Methods: This open-label, multi-center, single-arm, phase 2 study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received 2−4 lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1. Results: 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (IQR 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% (95% CI 60.6-78.2) and 70.8% (95% CI 61.5-79.0), respectively. The objective response rates were similar across all pre-specified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI 9.3-13.9) and 10.3 months (95% CI 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI 87.2-96.9). Grade {greater than or equal to}3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anaemia/decreased haemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred. Conclusions: Fluzoparib demonstrated promising anti-tumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population. Clinical Trial number: NCT03509636