FDA News

FDA expands Lynparza approval for gynecologic cancer

The FDA expanded the approval of olaparib to include its use in combination with bevacizumab for first-line maintenance treatment of certain women with advanced epithelial ovarian, fallopian tube or primary peritoneal cancers.

The approval applies to use of olaparib (Lynparza; AstraZeneca, Merck) and bevacizumab (Avastin, Genentech) by women who achieved complete or partial response to first-line platinum-based chemotherapy, and whose cancer is associated with homologous recombination deficiency-positive status defined either by a deleterious or suspected deleterious BRCA mutation and/or genomic instability.

The FDA also approved the Myriad myChoice CDx (Myriad Genetics) test as a companion diagnostic for olaparib.

Olaparib (Lynparza; AstraZeneca, Merck) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment of BRCA-mutated advanced ovarian cancer, maintenance treatment of women with recurrent ovarian cancer and treatment of women with germline BRCA-mutated advanced ovarian cancer. It also is indicated for treatment of germline BRCA-mutated, HER2-negative metastatic breast cancer, as well as first-line maintenance for germline BRCA-mutated metastatic pancreatic cancer.

The agency based the approvals on results of the randomized, placebo-controlled PAOLA-1 trial, which included 806 women with advanced high-grade epithelial ovarian cancer, fallopian tube or primary peritoneal cancers who received first-line platinum-based chemotherapy and bevacizumab.

In the double-blind, multicenter trial, researchers randomly assigned 537 women to maintenance therapy with olaparib dosed at 300 mg twice daily plus bevacizumab dosed at 15 mg/kg every 3 weeks. Olaparib treatment began a minimum of 3 weeks and maximum of 9 weeks after final chemotherapy dose, and treatment continued for up to 2 years or until disease progression or unacceptable toxicity.

The other 269 women received maintenance therapy with placebo plus bevacizumab.

Researchers stratified women by first-line treatment outcome and BRCA mutation status.

Investigator-assessed PFS served as the major efficacy outcome measure. OS served as an additional efficacy endpoint.

As Healio previously reported, results showed significantly longer median PFS in the olaparib group compared with the placebo group (22.1 months vs. 16.6 months; HR = 0.59; 95% CI, 0.49-0.72).

Among patients with BRCA-mutated tumors, median PFS was 37.2 months in the olaparib group vs. 21.7 months in the placebo group (HR = 0.31; 95% CI, 0.2-0.47). Among women without BRCA mutations, median PFS was 18.9 months in the olaparib group vs. 16 months in the placebo group (HR = 0.71; 95% CI, 0.58-0.88).

Women with homologous recombination deficiency (HRD)-positive disease had median PFS of 37.2 months with olaparib vs. 17.7 months with placebo (HR = 0.33; 95% CI, 0.25-0.45). Women with HRD-positive status without BRCA mutations had median PFS of 28.1 months with olaparib and 16.6 months with placebo. Women with HRD-negative or unknown status had median PFS of 16.9 months with olaparib and 16 months with placebo.

OS data were not mature.

The most common adverse events reported with the olaparib-bevacizumab combination included nausea, fatigue, anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection and headache.

The FDA previously granted priority review to olaparib in combination with bevacizumab for this indication.

The FDA expanded the approval of olaparib to include its use in combination with bevacizumab for first-line maintenance treatment of certain women with advanced epithelial ovarian, fallopian tube or primary peritoneal cancers.

The approval applies to use of olaparib (Lynparza; AstraZeneca, Merck) and bevacizumab (Avastin, Genentech) by women who achieved complete or partial response to first-line platinum-based chemotherapy, and whose cancer is associated with homologous recombination deficiency-positive status defined either by a deleterious or suspected deleterious BRCA mutation and/or genomic instability.

The FDA also approved the Myriad myChoice CDx (Myriad Genetics) test as a companion diagnostic for olaparib.

Olaparib (Lynparza; AstraZeneca, Merck) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment of BRCA-mutated advanced ovarian cancer, maintenance treatment of women with recurrent ovarian cancer and treatment of women with germline BRCA-mutated advanced ovarian cancer. It also is indicated for treatment of germline BRCA-mutated, HER2-negative metastatic breast cancer, as well as first-line maintenance for germline BRCA-mutated metastatic pancreatic cancer.

The agency based the approvals on results of the randomized, placebo-controlled PAOLA-1 trial, which included 806 women with advanced high-grade epithelial ovarian cancer, fallopian tube or primary peritoneal cancers who received first-line platinum-based chemotherapy and bevacizumab.

In the double-blind, multicenter trial, researchers randomly assigned 537 women to maintenance therapy with olaparib dosed at 300 mg twice daily plus bevacizumab dosed at 15 mg/kg every 3 weeks. Olaparib treatment began a minimum of 3 weeks and maximum of 9 weeks after final chemotherapy dose, and treatment continued for up to 2 years or until disease progression or unacceptable toxicity.

The other 269 women received maintenance therapy with placebo plus bevacizumab.

Researchers stratified women by first-line treatment outcome and BRCA mutation status.

Investigator-assessed PFS served as the major efficacy outcome measure. OS served as an additional efficacy endpoint.

As Healio previously reported, results showed significantly longer median PFS in the olaparib group compared with the placebo group (22.1 months vs. 16.6 months; HR = 0.59; 95% CI, 0.49-0.72).

Among patients with BRCA-mutated tumors, median PFS was 37.2 months in the olaparib group vs. 21.7 months in the placebo group (HR = 0.31; 95% CI, 0.2-0.47). Among women without BRCA mutations, median PFS was 18.9 months in the olaparib group vs. 16 months in the placebo group (HR = 0.71; 95% CI, 0.58-0.88).

Women with homologous recombination deficiency (HRD)-positive disease had median PFS of 37.2 months with olaparib vs. 17.7 months with placebo (HR = 0.33; 95% CI, 0.25-0.45). Women with HRD-positive status without BRCA mutations had median PFS of 28.1 months with olaparib and 16.6 months with placebo. Women with HRD-negative or unknown status had median PFS of 16.9 months with olaparib and 16 months with placebo.

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OS data were not mature.

The most common adverse events reported with the olaparib-bevacizumab combination included nausea, fatigue, anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection and headache.

The FDA previously granted priority review to olaparib in combination with bevacizumab for this indication.