ANNIE Data Support Anlotinib/Niraparib Combo as Late-line Option in Platinum-resistant Ovarian Cancer

The TKI anlotinib plus the PARP inhibitor niraparib continued to provide overall survival benefit with an acceptable safety profile when given to patients with platinum-resistant recurrent ovarian cancer.

Anlotinib/Niraparib Combo in Platinum-resistant 

Ovarian Cancer | Image Credit: © Lars Neumann -

Anlotinib/Niraparib Combo in Platinum-resistant

Ovarian Cancer | Image Credit: © Lars Neumann -

The TKI anlotinib (AL3818) plus the PARP inhibitor niraparib (Zejula) continued to provide overall survival (OS) benefit with an acceptable safety profile when given to patients with platinum-resistant recurrent ovarian cancer, according to data from a sensitivity analysis of the phase 2 ANNIE trial (NCT0437607) presented at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

Patients treated with the combination (n = 40) experienced a median OS of 18.2 months (95% CI, 12.1-not reached) in the final survival analysis. Notably, 18 deaths had occurred by the time of data cutoff, which was July 7, 2022.1

“The combination of niraparib and anlotinib show promising safety and efficacy in subsequent long-term follow-up and should be an option for [patients with] platinum-resistant ovarian cancer in late-line treatment,” lead study author Guochen Liu, MD, of Sun Yat-Sen University Cancer Center in Guangzhou, China, and colleagues, wrote in a poster on the data.

There is a lack of effective, viable treatment options for patients with platinum-resistant ovarian cancer, who have a historically poor prognosis. However, prior research has shown that the addition of a PARP inhibitor to antiangiogenic agents can produce antitumor activity in this disease setting.

Data from the ANNIE trial were previously published in eClinicalMedicine, and showed that at a median follow-up of 15.4 months (95% CI, 12.6-17.7) and a data cutoff date of January 31, 2022, the overall response rate (ORR) with the combination in the intention-to-treat population was 50% (95% CI, 33.8%-66.2%). Among those who responded, 19 had partial responses and 1 achieved a complete response. The median progression-free survival was 9.2 months (95% CI, 7.4-11.9) with the doublet, and the median OS was 15.3 months (95% CI, 13.9-not evaluable).2

At the 2023 SGO Annual Meeting, investigators shared updated survival and safety results, which had a median follow-up of 19.0 months and a data cutoff date of July 7, 2022.1

The multicenter, single-arm study included patients between the ages of 18 and 70 years with histologically confirmed recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer.1,2 To be eligible for enrollment, patients must have experienced disease recurrence less than 6 months after the cessation of their last platinum-based therapy. Patients were also required to have measurable disease by RECIST v1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of longer than 16 weeks, and acceptable organ function. Patients with prior PARP inhibitor exposure were excluded.

Of the 40 patients enrolled, 34 exhibited high-grade serous carcinoma and 6 had other histopathology.1 At the time of diagnosis, patients predominantly had FIGO stage III (n = 31) or stage IV (n = 6) disease, and the majority received prior antiangiogenic treatment (n = 27). Regarding ECOG performance status, 25 patients had a status of 0, and 15 had a status of 1. Germline BRCA mutations were identified in 5 patients, and 35 had BRCA wild-type disease.

All patients were administered oral niraparib according to baseline body weight. Those who weighed less than 77 kg were administered 200 mg of niraparib; the remaining patients received the agent at 300 mg. Patients also received a once-daily, 10-mg dose of anlotinib administered for days 1 to 14 of each 21-day cycle. Treatment continued until disease progression or treatment intolerance.

The study’s primary end point was ORR, and key secondary end points included PFS, OS, disease control rate, and safety.Safety was measured by the incidence, severity, and drug-relatedness of adverse effects (AEs).

At the time of data cutoff, 1 patient remained on treatment. The remaining 39 patients discontinued treatment due to disease progression (n = 27), AEs (n = 5), patient request (n = 6) or a protocol violation (n = 1; received chemotherapy).

Forty-eight percent of patients required a dose reduction of niraparib, and 53% required a dose reduction of anlotinib; 28% of patients needed dose reductions for both agents. AEs led to dose reduction of anlotinib included hand-foot syndrome, rash, anorexia, and hypertriglyceridemia. Dose reduction of niraparib was primarily attributed to hematological AEs. Dose reductions primarily occurred during the first month of treatment.

Ten percent of patients discontinued both agents due to toxicity. Investigators did not report any treatment-related deaths or incidence of myelodysplastic syndrome.

The safety profile of the regimen in the long-term analysis was consistent with previously reported data. Common any-grade AEs consisted of leukopenia (45%), hand-foot syndrome (43%), thrombocytopenia (38%), and neutropenia (35%). Additionally, the most prevalent treatment-related AEs that were grade 3 or greater were neutropenia (18%), hand-foot syndrome (15%), anemia (13%), thrombocytopenia (10%), and leukopenia (10%).


  1. Liu G, Xian B, Li J, et al. Updated survival and safety results from the phase 2 study (ANNIE) of anlotinib and niraparib dual therapy evaluation in platinum-resistant recurrent ovarian cancer. Presented at: 2023 Annual Meeting on Women’s Cancer; March 25-28; Tampa, Florida. Poster 314.
  2. Liu G, Feng Y, Li J, et al. A novel combination of niraparib and anlotinib in platinum-resistant ovarian cancer: Efficacy and safety results from the phase II, multi-center ANNIE study. EClinicalMedicine. Published November 30, 2022. doi:10.1016/j.eclinm.2022.101767
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