At an 18-month study of the OVARIO phase 2 trial (NCT03326193), progressive survival benefit (PFS) continued in the majority of patients with advanced ovarian cancer previously treated with facial platinum-based chemotherapy and bevacizumab (Avastin) and went on to receive a therapeutic combination of niraparib (Zejula) and bevacizumab. These findings were presented at the 2021 Society for Gynecological Oncology Virtual Annual Meeting on Female Cancer.1
Results from the one-arm, open-label study showed that 62% (40 events; 95% CI, 52% -71%) of patients in the total treatment population (n = 105) were still free of progression at 18 months later. This was followed by a 6-month follow-up which showed that 90% (95% CI, 82% -95%) of patients were still progressive and a 12-month follow-up where 75% (95% CI, 66 % -83%) all patients were still free of progress.
The study evaluated newly diagnosed patients with high serous or endometrioid stage IIIB to epithelial ovarian IV, fallopian tube, or primary peritoneal cancer who had a previous complete response (CR), partial response (PR), or any evidence of disease outcome of facial platinum-based chemotherapy in addition to bevacizumab. Patients were treated with niraparib and bevacizumab to develop PFS.
Previous data had shown the benefit of niraparib as a monotherapy to improve PFS, but the AVANOVA study (NCT02336193) showed a significant improvement in PFS (HR, 0.35; 95% CI, 0.21–0.57, P. <.0001) for combination-treated patients compared with monotherapy,2 lead researchers to take a closer look at the combination with OVARIO. The primary endpoint was SDP level at 18 months with secondary endpoints including total survival (OS) and safety.
Researchers also divided the patients into 3 other sub-peers based on the biomarker status of the patients, with 47% (n = 49) of patients having a homologous reflex deficiency (HRd) with 28 % (n = 29) of these patients HRd BRCA mutated and 15% (n = 16) with HRd BRCA wild type mutation in their cancer. Thirty-six percent of patients (n = 38) showed HR ability (HRp) and 17% (n = 18) had an inclusion test, failed a test, or had no print to enough to test their HR status (HRnd).
“Inhibition of vascular endothelial growth factor can lead to acute hypoxia that may lead to genomic instability by altering DNA damage repair pathways, including homologous replication,” the investigators, led by Melissa M. Hardesty, MD, MPH, of the Alaska Women ‘s Cancer Center, said they wrote in their poster presentation of the data. “Therefore, it is assumed that the bevacizumab can sensitize tumors to polymerase (ADP-ribose) (PARPi) inhibitors. ”
These HRd, HRp, and HRnd groups also exhibited enhanced PFS levels with the combination of niraparib and bevacizumab at the 18-month follow-up, with SDP levels of 76% (95% CI, 61% –87% ), 47% (95% CI, 31% –64%), and 56% (95% CI, 31% –78%), respectively. The overall HRd group showed the highest SDP levels of the biomarker-matched subgroups through the follow-up with 98% at the 6-month follow-up and 88% at 12 months.
Patients on trial were 60-years-old with 66 patients with an ECOG performance score of 0, and the most common diagnosis rate was stage IIIC cancer in 71 patients. One hundred patients had serous disease at the time of diagnosis, 4 had endometroid, and 1 patient had unknown histology. Seventy-four patients had a primary tumor site, 19 patients had cancer in the fallopian tube, and 12 had primary peritoneal cancer. All patients were given either 200 mg ( 78%) or 300 mg (22%) of niraparib daily based on baseline body weight and platelet count and was initiated within 12 weeks of completion of face treatment. This was given in addition to bevacizumab at 15 mg / kg every 3 weeks.
Safety was the high point of completion of the study, which researchers found that the combination of niraparib and bevacizumab showed consistent adverse effects with those previously seen with all drugs as monotherapy; no new safety marks were seen. However, 99% of patients reported a treatment-related adverse event (TEAE) of any degree with 27% of patients discontinuing due to treatment-related TEAE. According to the researchers, this rate of treatment discontinuation was consistent with other PARPi plus bevacizumab studies because the rate is higher among combination therapies compared to monotherapy.
Seventy-seven percent of patients experienced level 3 or higher treatment-related TEAE, which included thrombocytopenia (39%), muscle weakness (10%), anemia (34%). ), nausea (1%), hip tension (27%), proteinuria (5%), headache (6%), and neutropenia (12%). The most common TEAE associated with treatment of any degree was thrombocytopenia in 70% of patients, followed by obesity (57%), anemia (52%), and nausea (52%).
References
1. Hardesty M. Phase 2 OVARIO Study of Niraparib + Bevacizumab Therapy in Advanced Ovarian Cancer After Platinum-Based Chemacizumab Chemotherapy. Poster on display at: Society of Gynecological Oncology 2021 Significant Annual Meeting on Women’s Cancer; March 19-21, 2021; Virtually. Poster 22.
2. Mirza MR, Lundqvist EÅ, Birrer MJ, et al; AVANOVA Detectors. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2 / ENGOT-ov24): randomized trial, stage 2, dominance. Lancet Oncol. 2019; 20 (10): 1409-1419. doi: 10.1016 / S1470-2045 (19) 30515-7