by Dr. C.H. Weaver M.D. updated 12/2018
Data from the TOPACIO trial of Zejula (niraparib) in combination with an anti-PD-1 monoclonal antibody, Keytruda® (pembrolizumab) were featured at the 2018 Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in New Orleans, Louisiana. Preliminary results from the study suggest that the combination of Zejula and Keytruda could provide meaningful clinical benefit to patients with platinum resistant ovarian cancer, regardless of biomarker status.1
About Platinum Resistant Ovarian Cancer
Each year in the United States, roughly 22,000 women are diagnosed with ovarian cancer and more than 15,000 die of the disease. Treatment for ovarian cancer commonly involves surgery and/or chemotherapy. Women who experience cancer progression during or within six months of treatment with a platinum-based chemotherapy regimen are considered to have platinum-resistant cancer. Patients with platinum-resistant or platinum-refractory ovarian cancer have limited treatment options available to them. Approximately 10,000 women in the US begin treatment for platinum-resistant or refractory ovarian cancer each year.2
About Zejula® (Niraparib)
Zejula is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
About Keytruda (pembrolizumab)
The cancer immunotherapy strategy known as programmed cell death 1 (PD-1) has generated great excitement for its ability to help the immune system recognize, and attack cancer. Keytruda is a fully humanized monoclonal antibody that binds with high-affinity to the PD-1 receptor that helps to restore the body’s immune system in fighting cancer. It creates its anti-cancer effects by blocking a specific protein used by cancer cells called PD-L1, to escape an attack by the immune system. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 are called checkpoint inhibitors and enhance the ability of the immune system to fight cancer. Once PD-L1 is blocked, cells of the immune system are able to identify cancer cells as a threat, and initiate an attack to destroy the cancer.
TOPACIO is an early stage clinical trial designed to evaluate the safety and potential effectiveness of Zejula combined with the checkpoint inhibitor Keytruda in patients with recurrent, platinum-resistant ovarian cancer. Initial results for 62 patients were presented at the SGO meeting. Patients were heavily pretreated; 45% had been treated with 3 or more prior lines of chemotherapy, 97% with a prior taxane, 63% received prior Avastin (bevacizumab), and 29% were platinum refractory.
The combination of Zejula with Keytruda was well tolerated. Overall 25% of patients experienced a response to treatment and a disease control rate of 68% was reported. Response rates were not dependent on BRCA or HRD biomarker status. 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.
The response rate of 25% compares favorably with other developed treatment options. Patients with platinum-resistant or refractory ovarian cancer have response rate of less than 15% to currently available therapies.1,2 Historical response to Zejula and other 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.
Currently a registration study is being planned to confirm these early results of Zejula and a PD-1 inhibitor. The trial will use TSR-042, another anti-PD-1 antibody instead of keytruda.
- NCCN clinical practice guidelines in oncology. Ovarian cancer, including fallopian tube cancer and primary peritoneal cancer. Version 2. 2018. [accessed 03.25.18]
- Gelmon, et al. Lancet Oncol 2011; Sandhu, et al. Lancet Oncol
- Fong J Clin Onocol2010, Domchek, et al. Gyn Oncol
- Hamanishi, et al. ASCO2015 (some patients had clear cell cancer); Varga, et al. ASCO
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