Ting Deng,1,* Lei Yan,2,* Jing Li,1 Guochen Liu,1 Aijun Yin,3 Yanling Feng,1 Min Zheng,1 Chuyao Zhang,1 He Huang,1 Qidan Huang,1 An Lin,4 Jie Jiang,3 Beihua Kong,3 Jihong Liu1,* 

1Department of Gynecological Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China; 2Department of Health Management Center, The First Affiliated Hospital of Jinan University, The First Clinical Medical College of Jinan University, Guangzhou, People’s Republic of China; 3Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 4Department of Gynecology, Fujian Provincial Cancer Hospital, Fuzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jihong Liu, Department of Gynecological Oncology, Sun Yat-Sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, People’s Republic of China, Tel +86-020-87341615, Email liujh@sysucc.org.cn

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.
Conclusion: 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.
Plain Language Summary: Platinum-resistant recurrent ovarian cancer patients face limited treatment options. This study evaluated the efficacy and safety of combining niraparib (a PARP inhibitor) and anlotinib (an anti-angiogenic drug). Results showed the combination significantly prolonged overall survival, offering new hope to patients. A multidisciplinary approach controlled key side effects: beta-blockers stabilized blood pressure/heart rate, while lipid-lowering therapy-maintained cholesterol/triglyceride levels. Hematological adverse events matched those from prior single-drug studies, with no new safety concerns. This therapy is effective and safely manageable via multidisciplinary collaboration, providing clinicians a model to improve patient outcomes and quality of life.

Keywords: ovarian cancer, niraparib, anlotinib, long-term safety, multidisciplinary management