Zejula Shows Potential as More Than Just Maintenance Therapy

In the QUADRA study, treatment with Zejula (niraparib) demonstrated durable responses among women with relapsed or refractory ovarian cancer, regardless of BRCA mutation.
BY Kristie L. Kahl
PUBLISHED June 23, 2018
Treatment with Zejula (niraparib) led to durable responses beyond those seen in patients with BRCA-positive late-line ovarian cancer, according to results from the QUADRA study presented at the 2018 American Society of Clinical Oncology Annual Meeting.

Currently, PARP inhibitors are approved for the treatment of women with ovarian cancer, but only for those with BRCA mutations. In addition, ovarian cancer is a disease that oftentimes recurs – leading to an unmet medical need in this treatment landscape.

“The main problem in ovarian cancer is women present with advanced disease. Chemotherapy and surgery work pretty well in the first-line setting, but the problem is that 85 percent of women will have their cancer recur. And once it has recurred once, it is going to keep recurring,” Martin Huber, M.D., senior vice president and chief medical officer at TESARO, said in an interview with CURE.

“The real unmet medical need is that each time you treat them, the interval that the chemotherapy works for gets shorter and shorter,” he added. “What ends up happening, women use three or four lines of chemotherapy treatment, and they are basically running out of options.”

In the maintenance setting of women with platinum-responsive relapsed ovarian cancer, Zejula demonstrated improved progression-free survival (PFS) rates compared with placebo. In particular, the agent was effective regardless of BRCA mutation homologous recombination deficiency (HRD) status.

In the open-label, single arm, phase 2 QUADRA trial, researchers evaluated the safety and efficacy of Zejula – 300 mg once daily – as a fourth-line or greater treatment in 463 patients with ovarian cancer, regardless of platinum or biomarker status.

Objective response rate (ORR) served as the primary endpoint of the study, while secondary endpoints included durability of response, disease control rate, PFS, overall survival (OS), safety and tolerability. The primary efficacy population included fourth or fifth line patients who were previous PARP inhibitor naïve, platinum sensitive, and HRD positive (45 patients).

Of note, less than 20 percent of patients had a BRCA mutation, 27 percent received Zejula as a sixth or later line therapy, two-thirds were platinum resistant or refractory (33 percent and 35 percent, respectively), and 48 percent were HRD positive. In addition, the majority of platinum sensitive patients were considered platinum ineligible and 62 percent had received prior Avastin (bevacizumab).

Of the 45 patients in the primary efficacy population, ORR was 29 percent.

Those who were fourth or later line, HRD-positive and platinum sensitive (51 patients) experienced an ORR of 27 percent, which included a disease control rate (complete response, partial response and stable disease) of 69 percent, and a duration of response of 9.2 months.

In patients treated with Zejula as a fourth-line therapy or later, patients with a BRCA mutation and those who were HRD-positive and platinum sensitive had clinical benefit rates of 53 percent and 49 percent, respectively, for at least 16 weeks.

Across the entire patient population, median duration of response was 9.4 months, with an estimated 44 percent of all responses lasting 12 months or more.

Median OS in all patients treated with Zejula as a fourth line therapy or later was 17.2 months; 16.6 months in HRD-negative or unknown patients, 19 months in HRD-positive patients; and 26 months in patients with BRCA mutations.

The most common grade 3/4 side effects included anemia (26.3 percent) and thrombocytopenia (20.5 percent), which were generally managed with dose modifications.

Huber noted TESARO plans to use these results to submit a supplemental new drug application to the Food and Drug Administration (FDA) by the end of this year.

“What is important is that response rate is similar to what we have seen in the BRCA population. So, what we were very excited by is that we saw efficacy beyond the BRCA population,” said Huber. “That is leading us to now look at our opportunities for doing a regulatory file and making this available to not only treatment for women with a BRCA mutation, but women who have ovarian cancer beyond the BRCA mutation.”
 
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