FDA approvals

FDA approves Zejula for maintenance treatment of gynecologic cancers

The FDA today approved niraparib for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers who achieved complete or partial response to platinum-based chemotherapy.

“Despite high response rates to platinum-based treatment in recurrent ovarian cancer patients, the effectiveness of such chemotherapy diminishes over time,” Ursula Matulonis, MD, director of gynecologic oncology at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, said in a company-issued press release. “Unfortunately, PFS generally gets shorter after each subsequent treatment with a platinum-based chemotherapy regimen. Therefore, a treatment like Zejula that can increase PFS after platinum therapy is very meaningful to patients and their families.”

Ursula Matulonis
Ursula Matulonis

The approval of niraparib (Zejula, Tesaro) — a PARP inhibitor — was based on results of the randomized ENGOT-OV16/NOVA trial, which included 553 patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers who had received at least two prior treatments with platinum-based chemotherapy. All patents were in complete or partial response to their last chemotherapy treatment. Based on results from the BRACAnalysis CDx (Myriad Genetics) test, patients were categorized as having germline BRCA mutations (n = 203) or no germline BRCA mutations (n = 350).

Researchers randomly assigned patients 2:1 to receive 300 mg daily oral niraparib or placebo within 8 weeks of their last therapy.

Patients assigned niraparib achieved significantly longer PFS in patients with germline BRCA mutations (21 months vs. 5.5 months; HR = 0.26; 95% CI, 0.17-0.41) and without BRCA mutations (9.3 months vs. 3.9 months; HR = 0.45; 95% CI, 0.34-0.61).

“Until recently, there have been few treatment advances for women with recurrent ovarian cancer and even fewer options available for women who do not harbor BRCA mutations,” Matulonis said in the release. “We are excited to have the opportunity to offer appropriate patients an oral, once-daily maintenance treatment that reduces the risk for cancer progression and extends the time between courses of chemotherapy for patients who have few treatment options.”

Safety data were available from 367 patients. The most common adverse events included thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, alanine transaminase and aspartate transaminase elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash and hypertension.

A greater proportion of patients assigned niraparib experienced grade 3 to grade 4 hypertension (9% vs. 2%).

Further, five patients (1.4%) assigned niraparib and two patients (1.1%) assigned placebo developed myelodysplastic syndrome or acute myeloid leukemia.

FDA recommends 300 mg niraparib once daily with or without food.

“The approval of Zejula, the first maintenance therapy approved in the U.S. for recurrent ovarian cancer, is extremely encouraging for the ovarian cancer community,” Mansoor Raza Mirza, MD, ENGOT-OV16/NOVA study chair and medical director of the Nordic Society of Gynaecological Oncology, said in the press release. “The unique design of the NOVA study … allowed us to determine that Zejula provides significant PFS improvement in a very broad patient population. Having the option of prescribing Zejula without the need for a diagnostic test could fundamentally change the way we treat this disease from ‘watch and wait’ after a response to chemotherapy, to active treatment.

“With the significant increase in PFS observed in NOVA, I believe that we are changing the course of disease for patients with ovarian cancer, regardless of platinum sensitivity and independent of BRCA mutation or biomarker status,” Mirza added.

The FDA today approved niraparib for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers who achieved complete or partial response to platinum-based chemotherapy.

“Despite high response rates to platinum-based treatment in recurrent ovarian cancer patients, the effectiveness of such chemotherapy diminishes over time,” Ursula Matulonis, MD, director of gynecologic oncology at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, said in a company-issued press release. “Unfortunately, PFS generally gets shorter after each subsequent treatment with a platinum-based chemotherapy regimen. Therefore, a treatment like Zejula that can increase PFS after platinum therapy is very meaningful to patients and their families.”

Ursula Matulonis
Ursula Matulonis

The approval of niraparib (Zejula, Tesaro) — a PARP inhibitor — was based on results of the randomized ENGOT-OV16/NOVA trial, which included 553 patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers who had received at least two prior treatments with platinum-based chemotherapy. All patents were in complete or partial response to their last chemotherapy treatment. Based on results from the BRACAnalysis CDx (Myriad Genetics) test, patients were categorized as having germline BRCA mutations (n = 203) or no germline BRCA mutations (n = 350).

Researchers randomly assigned patients 2:1 to receive 300 mg daily oral niraparib or placebo within 8 weeks of their last therapy.

Patients assigned niraparib achieved significantly longer PFS in patients with germline BRCA mutations (21 months vs. 5.5 months; HR = 0.26; 95% CI, 0.17-0.41) and without BRCA mutations (9.3 months vs. 3.9 months; HR = 0.45; 95% CI, 0.34-0.61).

“Until recently, there have been few treatment advances for women with recurrent ovarian cancer and even fewer options available for women who do not harbor BRCA mutations,” Matulonis said in the release. “We are excited to have the opportunity to offer appropriate patients an oral, once-daily maintenance treatment that reduces the risk for cancer progression and extends the time between courses of chemotherapy for patients who have few treatment options.”

Safety data were available from 367 patients. The most common adverse events included thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, alanine transaminase and aspartate transaminase elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash and hypertension.

A greater proportion of patients assigned niraparib experienced grade 3 to grade 4 hypertension (9% vs. 2%).

Further, five patients (1.4%) assigned niraparib and two patients (1.1%) assigned placebo developed myelodysplastic syndrome or acute myeloid leukemia.

FDA recommends 300 mg niraparib once daily with or without food.

“The approval of Zejula, the first maintenance therapy approved in the U.S. for recurrent ovarian cancer, is extremely encouraging for the ovarian cancer community,” Mansoor Raza Mirza, MD, ENGOT-OV16/NOVA study chair and medical director of the Nordic Society of Gynaecological Oncology, said in the press release. “The unique design of the NOVA study … allowed us to determine that Zejula provides significant PFS improvement in a very broad patient population. Having the option of prescribing Zejula without the need for a diagnostic test could fundamentally change the way we treat this disease from ‘watch and wait’ after a response to chemotherapy, to active treatment.

“With the significant increase in PFS observed in NOVA, I believe that we are changing the course of disease for patients with ovarian cancer, regardless of platinum sensitivity and independent of BRCA mutation or biomarker status,” Mirza added.