A combination of Keytruda (pembrolizumab) and Zejula (niraparib) has shown promising and durable response rates in triple-negative breast cancer patients, regardless of their BRCA mutational status, Phase 1/2 trial data show.
The trial, called TOPACIO (NCT02657889), is assessing the combination in triple-negative breast cancer patients with advanced or metastatic disease and in women with ovarian cancer.
Results from the breast cancer group were recently presented at the 2018 American Society of Clinical Oncology Annual Meeting, in an oral presentation, titled “TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial.”
PARP enzymes act as DNA damage sensors, binding to the sites of DNA damage and contributing to their repair. Cancer cells that have defects in other DNA repair mechanisms — such as those with mutated BRCA tumor suppressor genes — rely on PARP to survive and proliferate.
Zejula, developed by TESARO, is a PARP inhibitor that leads to the accumulation of DNA damage and ultimately to the death of these cancer cells.
The medicine is already approved as a maintenance therapy for ovarian cancer patients, and has shown promise in breast cancer patients with mutations in the BRCA genes.
TOPACIO is a Phase 1/2 trial assessing if Keytruda and Zejula together can increase response rates in patients with advanced or metastatic triple-negative breast cancer (TNBC) and recurrent ovarian cancer.
As of April 2018, 46 of the TNBC patients were able to be assessed for an initial response. Among them, 15 had BRCA mutations, and five had genetic alterations in other DNA repair genes.
To date, three patients had complete responses, 10 had partial tumor reductions, and 10 had their disease stabilized with the treatment. This represents an overall response rate of 28% and a disease control rate of 50%.
As expected, patients with BRCA mutations had the best response rates, at 60%, followed by those with mutations in other DNA repair genes, at 55%, and those who were positive for the PD-L1 protein — a biomarker that predicts response to Keytruda — at 36%.
Overall, the 15 patients with BRCA mutations lived for a median of 8.3 months without their disease progressing, which is better than the three to five months seen with standard chemotherapy, or the rates seen with either agent alone.
The study is ongoing, with eight of the responders still receiving the combination, including five patients who experienced a beneficial clinical effect for approximately one year.
In general the treatment has been well-tolerated, with the most common serious events being anemia and reduced blood platelet levels.
“The TOPACIO results support the advancement of combination studies in ovarian cancer and breast cancers and we have initiated preparations for registrational trials of niraparib in combination with TSR-042 [a company’s proprietary anti-PD1 therapy] in these settings,” Mary Lynne Hedley, PhD, president and chief operating officer of TESARO, said in a press release.