Adverse Event Management in Patients with Platinum-Resistant Ovarian Cancer Treated with Niraparib and Anlotinib: Updates from the Phase II, Multi-Center ANNIE Study

Abstract Background: The primary analysis of the ANNIE study demonstrated promising anti-tumor activity of the niraparib-anlotinib combination in platinum-resistant recurrent ovarian cancer (PROC). We report updated overall survival (OS) and safety data and the management of key treatment-emergent adverse event (TEAE) from the ANNIE study. Methods: In the multi-center, single-arm, phase 2 ANNIE study, enrolled patients received oral niraparib 200 mg or 300 mg (baseline bodyweight-directed) once daily and anlotinib 10 mg (12 mg before protocol amendment) once daily on days 1–14 of each 21-day cycle. Safety management involved a multidisciplinary team comprising specialist physicians, who performed monitoring and intervention for key comorbidities and TEAEs. Results: Forty patients were enrolled. After a median follow-up of 19.0 months, the updated median OS was 18.2 months (95% confidence interval: 12.1–not evaluable). The most common TEAEs were hypertension (n=22, 55%), leukopenia (n=18, 45%), hand-foot syndrome (n=17, 43%), thrombocytopenia (n=15, 38%), neutropenia (n=14, 35%), and hypertriglyceridemia (n=12, 30%). Hypertension and cardiovascular events were mostly managed by early interventions using beta-blockers. Hypertriglyceridemia was mostly managed using atorvastatin and simvastatin. Hematological toxicities were consistent with prior studies and no severe hematologic events occurred. Protocol amendment was implemented to reduce the incidence of hand-foot syndrome, while topical glucocorticoids and non-steroidal anti-inflammatory drugs were used in patients with apparent symptoms. Conclusions: The updated OS analysis showed sustained long-term efficacy of niraparib-anlotinib in PROC patients. The safety data reflected satisfactory tolerability and adverse event management, supporting the involvement of a multidisciplinary disease management team in ovarian cancer care. Clinical trial registration: NCT04376073