In a 7-to-5 vote, the FDA’s Oncologic Drugs Advisory Committee recommended the PARP inhibitor olaparib as first-line maintenance therapy for patients with germline BRCA-mutated metastatic pancreatic cancer whose disease did not progress after first-line treatment with platinum-based chemotherapy, AstraZeneca and MSD, Inc. reported in a press release.<br />
In a 7-to-5 vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended the PARP inhibitor olaparib (Lynparza) as first-line maintenance therapy for patients with germlineBRCA-mutated metastatic pancreatic cancer whose disease did not progress after first-line treatment with platinum-based chemotherapy, AstraZeneca and MSD, Inc. reported in a press release.1
“We are pleased with the ODAC’s recommendation for [olaparib] and the potential to bring a personalized, biomarker-targeted medicine to patients with germlineBRCA-mutated metastatic pancreatic cancer. Patients with advanced pancreatic cancer historically have faced poor outcomes due to the aggressive nature of the disease and limited treatment advances over the last few decades. We look forward to working with the FDA as it completes the review of our application,” José Baselga, executive director and vice president, Oncology Research and Development, AstraZeneca, said in a statement.
The ODAC hearing was called to discuss the supplemental new drug application (sNDA) for olaparib, which was submitted in October 2018 andgranted priority review by the FDA. The sNDA was submitted based on positive results from the phase III POLO trial.2,3
The POLO trial, which was previously reported byTargeted Oncology,showed a significant progression-free survival (PFS) benefit with olaparib maintenance compared with placebo in patients with germlineBRCA-mutated metastatic pancreatic cancer. The median PFS observed was 7.4 months versus 3.8 months with placebo (HR, 0.53; 95% CI, 0.35-0.82;P= .004). After 2 years of treatment, 22.1% of the patients treated with olaparib maintenance had not experienced progression of disease (PD). The rate of PFS at 2 years for patients in the placebo group was 9.6%.
The randomized, double-blind, placebo-controlled POLO trial divided patients into 2 arms following a 3:2 ratio. Patients were randomized within 6 weeks after their last dose of platinum-based chemotherapy. Subjects in the experimental arm received olaparib 300 mg twice daily and those in the comparator arm were given matched placebo twice daily doses. While enrolled in the study, patients were required to visit their treatment clinic weekly for a total of 4 weeks. These check-ins occurred on days 8, 15, 22, and 29. These patients received treatment continually until objective radiological disease progression as assessed by investigators per RECIST 1.1. Patients who progressed during the study were followed for a second progression, every 8 weeks until the time of the final study analysis.
The primary end point of the study was PFS. The study also measured overall survival, objective response rate, disease control rate, safety, and tolerability, as well as several other efficacy-related outcomes.
Candidates were eligible to enroll in the POLO trial if they had a histologically or cytologically confirmed pancreatic cancer for which they received initial chemotherapy for metastatic disease and had no evidence of PD on treatment. Patients also had to have measurable disease, documentedgBRCA1orgBRCA2mutations, and have received first-line platinum-based chemotherapy. Those who previously received a platinum as a curative treatment for a prior malignancy were also included.
Individuals were excluded from the trial if they hadgBRCA1orgBRCA2mutations that were deemed nondetrimental, experienced PD between the time of treatment on platinum-based chemotherapy and randomization in the study, had cytotoxic chemotherapy or nonhormonal targeted therapy within 28 days of the first cycle of study treatment, were exposed to an investigational drug within 30 days of starting the study, or had any previous treatment with olaparib or other PARP inhibitors.
“We are encouraged by the ODAC’s favorable vote for [olaparib] as a first-line maintenance therapy in germlineBRCA-mutated metastatic pancreatic cancer. This recommendation is a significant step towards reaching our goal to help patients with this deadly disease,” Roy Baynes, senior vice president and head of Global Clinical Development, chief medical officer, MSD Research Laboratories, stated to the press.
The FDA is not required to adhere to the recommendations of ODAC, however, following the hearing, the FDA will take the vote into consideration as it decides on the approval of olaparib as first-line maintenance for patients with germlineBRCA-mutated pancreatic cancer.