- Efficacy of niraparib in combination with an anti-PD-1 mAb surpasses historical efficacy benchmarks for PD-1 or PARP monotherapies in difficult-to-treat types of ovarian cancer, regardless of biomarker status
- Potential approach to reduce incidence of Grade 3 or 4 thrombocytopenia identified based on retrospective analysis of data from Phase 3 NOVA trial
“Patients with platinum-resistant or platinum-refractory ovarian cancer have limited treatment options available to them. Approximately 10,000 women in each of the US and EU begin treatment for platinum-resistant or refractory ovarian cancer each year,” said
“These data provide a compelling initial step in our ovarian cancer development strategy which is progressing from monotherapy ZEJULA utilized in PRIMA, NOVA and QUADRA to doublet and triplet combination approaches with anti-PD-1 antibodies and bevacizumab,” said
Phase 2 TOPACIO Data Demonstrate Activity in Platinum-Resistant and Platinum-Refractory Ovarian Cancer Patients, Regardless of Biomarker Status
TOPACIO is a Phase 1/2 clinical trial designed to evaluate the safety and efficacy of niraparib plus KEYTRUDA® (pembrolizumab) in patients with recurrent, platinum-resistant ovarian cancer or triple negative breast cancer. Niraparib administered orally, once-daily, at a dose of 200 milligrams is being evaluated in combination with 200 milligrams of pembrolizumab administered intravenously on day one of each 21-day treatment cycle in two patient cohorts; platinum-resistant/refractory ovarian cancer and triple-negative breast cancer. Endpoints include RECIST response rate, duration of response, disease control rate, progression-free survival and overall survival. Data presented at SGO were from the group of patients with ovarian cancer.
At the time of data cutoff, of the 62 patients enrolled, 60 were evaluable; 45% had been treated with 3 or more prior lines of chemotherapy, 97% with prior taxane, 63% received prior bevacizumab, and 29% were platinum refractory. The majority (73%) did not have a BRCA mutation. Data indicate an overall response rate (ORR; including CR and PR) of 25% and a disease control rate (DCR; CR+PR+SD) of 68%; ORR was 24% in the platinum refractory population. Response rates were not dependent on biomarker status; ORR was 26% (9/34) in patients without a tumor BRCA mutation (tBRCAwt), and 29% (7/24) in patients with HRD-negative tumors. Duration of response was immature, with 9 of 15 (60%) of responders remaining on treatment, and over one-half of patients with disease control continuing on treatment or having already received treatment for over 6 months.
For patients with platinum-resistant ovarian cancer, response to chemotherapy is 5-18%, including the most commonly prescribed regimen in the U.S., bevacizumab plus pegylated liposomal doxorubicin1. Platinum refractory patients typically have even lower response rates and NCCN treatment guidelines recommend clinical trials for these patients2. Historical response to PARP inhibitors is 5-10% in patients without BRCA mutations who have platinum resistant disease3 and 0-14% in those with BRCA mutations and platinum refractory disease4. Response rates of 10-15% have been reported with anti-PD-1 antibodies in this ovarian cancer population5.
The combination of niraparib with pembrolizumab was well tolerated with an incidence of Grade 3/4 thrombocytopenia of 9%. In addition to thrombocytopenia, the other most commonly observed Grade ≥3 adverse events included anemia (19%) and neutropenia (6%).
Abstracts containing additional data from the TOPACIO trial, including results from patients with platinum-resistant ovarian cancer and patients with triple-negative breast cancer, have been submitted to the
A Retrospective Analysis of Phase 3 ENGOT-OV16/NOVA Trial Identified Predictors of Early Dose Modification for Niraparib
A retrospective analysis of the Phase 3 NOVA trial identified two baseline characteristics, patient body weight less than 170 pounds (77 kilograms) or platelet count of <150,000/µL to be significant factors for Grade 3 or 4 thrombocytopenia. The incidence of thrombocytopenia in the first month in this population was 35% in the NOVA study vs 12% in those with higher weight and platelet counts. By month 4, of the patients who remained on treatment, 83% with body weight < 170lbs or platelet count of <150,000/µL at baseline were receiving a dose of niraparib <300 milligrams. With dose interruptions, this group’s average daily dose was 207 milligrams in the first two months of niraparib therapy in NOVA. Regardless, efficacy was uncompromised (HR: 1.01 (95%CI: 0.69, 1.48)) in patients receiving a 200 milligram versus 300 milligram dose of niraparib. Of note, in TOPACIO, where starting dose is 200 milligrams, a 9% incidence of Grade 3 or 4 thrombocytopenia was reported.
“This analysis provides physicians with new information to help quickly identify the most appropriate dose for each of their patients,” said Dr.
About ZEJULA® (Niraparib)
Niraparib is marketed in
ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in some clinical studies. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.
Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.
TSR-042 is a monoclonal antibody targeting PD-1 and was developed as part of the collaboration between
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1 Bevacizumab Prescribing Information
2 NCCN clinical practice guidelines in oncology. Ovarian cancer, including fallopian tube cancer and primary peritoneal cancer. Version 2. 2018. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf [accessed 03.25.18]
3 Gelmon, et al. Lancet Oncol 2011; Sandhu, et al. Lancet Oncol 2013
4 Fong J Clin Onocol 2010, Domchek, et al. Gyn Oncol 2016;
5 Hamanishi, et al.
Source: TESARO, Inc.