http://www.curetoday.com/articles/lynparza-data-published-as-fda-weighs-approval
Lynparza Data Published as FDA Weighs Approval

Jason Harris

New data shows that Lynparza (maintenance olaparib) reduced the risk of disease progression or death from platinum-sensitive, relapsed, BRCA-mutant ovarian cancer by 70 percent compared with placebo. Results from the phase 3 trial were published in The Lancet Oncology.

Based on new data from the trial, the Food and Drug Administration (FDA) had granted a priority review in March to a new drug application for Lynparza. The agency is scheduled to make its final decision on the poly (ADP-ribose) polymerase (PARP) inhibitor before the end of the year.

“Our results confirm that olaparib can achieve a significant prolongation of progression-free survival in this patient population with no appreciable detrimental effect observed for patients’ quality of life,” lead author Eric Pujade-Lauraine, M.D., Ph.D., University of Paris Descartes, and co-investigators wrote.

Between September 2013 and November 2014, investigators recruited 295 women for the trial. Eligible patients had a performance status of zero or one, and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer.

Patients were required to have a predicted deleterious, or suspected deleterious BRCA1/2 mutation based on either blood or tumor testing, and all patients had to consent to provide 2 blood samples for confirmatory germline BRCA1/2 mutation testing. Overall, 78 percent of patients assigned to Lynparza and 84 percent of those assigned to placebo had a BRCA1/2 mutation previously determined by local testing.

Patients were randomly assigned in a 2:1 ratio to 300 mg of Lynparza twice daily. Treatment continued until disease progression or until the investigator deemed that a patient was no longer benefiting from treatment.
Overall, 86 patients assigned to placebo discontinued the study, including 76 due to progression and 2 due to toxicity. A total of 112 patients in the experimental arm discontinued, including 75 due to progression and 22 due to toxicity. Eighty-three patients in the experimental group and 13 in the control group remained on-study at the September 19, 2016, data cutoff.

The investigators reported that the incidence of grade ≥3 adverse events (AEs) was low in both groups. Thirty-five patients (18 percent) in the Lynparza group experienced serious AEs compared with eight (8 percent) patients in the placebo group. The most common serious AEs in the Lynparza group were anemia (4 percent), abdominal pain (2 percent), and intestinal obstruction (2 percent). The most common serious AEs in the placebo group were constipation (2 percent) and intestinal obstruction (2 percent).

A total of 45 patients (23 percent) in the Lynparza group died during the study, including one patient who died of grade 5 acute myeloid leukemia. Twenty-seven (27 percent) of patients died in the placebo arm.

Four patients in the both groups experienced acute myeloid leukemia, myelodysplastic syndrome, and/or chronic myelomonocytic leukemia during the study and long-term follow-up. Overall, the incidence of all secondary malignancies during the study and long-term follow-up was six patients (3 percent) in the Lynparza group and five patients (5 percent) in the placebo group.
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