A new treatment option is now available for some patients with pancreatic cancer ― those who carry germline BRCA mutations can now be treated with the PARP inhibitor drug olaparib (Lynparza, AstraZeneca and Merck Sharp & Dohme).
The drug has been approved by the US Food and Drug Administration (FDA) for use as a first-line maintenance treatment of germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer.
This is in line with the recommendation for approval made by the FDA's Oncologic Drugs Advisory Committee at its 17 December meeting.
Olaparib is already approved for use in BRCA-mutated ovarian and breast cancers.
However, several other treatment options are already available for these two cancer types, whereas there are few options for pancreatic cancer. It also remains one of the most devastating of cancers ― survival rates are the lowest of the most common cancer types (the 5-year survival rate is only 2% to 9%).
"Metastatic pancreatic cancer patients have been waiting a long time for new therapy options for their devastating disease," commented Julie Fleshman, president and CEO of the patient advocacy group, Pancreatic Cancer Action Network.
"Today's approval of olaparib provides an exciting new treatment option for patients with germline BRCA-mutated metastatic pancreatic cancer," she said in a statement.
About 4% to 9% of patients with metastatic pancreatic cancer are thought to carry gBRCAms.
To find patients for the pivotal POLO trial, on which the new approval is based, researchers screened 3315 patients with metastatic pancreatic cancer; 247 (7.5%) were found to have BRCAms. Of those, 93 experienced disease progression, were ineligible, or declined randomization.
Near Doubling of PFS
The POLO trial was conducted in 154 patients with metastatic pancreatic cancer and germline BRCA mutations whose disease was stable after the patients underwent first-line platinum chemotherapy. They were randomly assigned in a 2:1 ratio to receive either olaparib or placebo as maintenance therapy.
The results showed that median progression-free survival was nearly doubled with olaparib compared with placebo (7.4 months vs 3.8 months; hazard ratio, 0.53; P = .004).
This study was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in 2019 and was simultaneously published in the New England Journal of Medicine, as reported by Medscape Medical News at the time.
Principal investigator Hedy L. Kindler, MD, medical director, gastrointestinal oncology, University of Chicago, concluded that olaparib "should become a new standard of care in patients with metastatic pancreatic cancer who have a germline BRCA mutation."
Approached for comment, Suzanne Cole, MD, a medical oncologist at UT Southwestern Medical Center, Dallas, said this study represents a "huge step forward.
"This is the first time that a targeted medication has been successful in stopping the growth of metastatic pancreatic cancer in people who carry the BRCA mutation," with many patients having "dormant" disease, she said.
"Now that we have a targeted medication that can benefit patients who have the BRCA mutation when they present with metastatic pancreatic cancer, it is our duty to search for this genetic mutation in all patients with metastatic pancreatic cancer so that we can identify those people who can benefit," she told Medscape Medical News at ASCO's annual meeting.
Cole added that it is "good medical practice to pay attention to what is going on in the family and whether there are cancers that we know are related to BRCA mutations...to tip you off that [you] may need to be searching for the BRCA mutation in your own patient."
More Details From Clinical Trial
In a press release about the new approval, the manufacturer gives a few more details regarding the results from the POLO trial, which the company funded.
It notes that for patients who had measurable disease at baseline, 23% responded to olaparib, vs 12% with placebo. The median duration of treatment was more than 2 years (24.9 months vs 3.7 months with placebo).
However, overall survival (a secondary endpoint) did not differ at the interim analysis (18.9 months for olaparib vs 18.1 months for placebo).
The safety and tolerability profile of olaparib in the POLO trial was in line with that observed in prior clinical trials, the company said. The most common adverse events (AEs) that occurred in more than 20% of patients were fatigue/asthenia (60%), nausea (45%), abdominal pain (29%), diarrhea (29%), anemia (28%), decreased appetite (25%), and constipation (23%). The most common AEs of grade ≥3 were anemia (11%), fatigue/asthenia (5%), decreased appetite (3%), abdominal pain (2%), vomiting (1%), and arthralgia (1%). AEs led to dose reduction in 16% of patients who received olaparib; 5% of patients discontinued treatment.
The POLO received funding from AstraZeneca, Myriad Genetic Laboratories, and Merck Sharp & Dohme Corp. Many of the authors have relationships with pharmaceutical companies, as detailed in the original article.
N Eng J Med. Published June 2, 2019. Abstract
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Cite this: New Option in Pancreatic Cancer: Olaparib for BRCA Mutations - Medscape - Dec 30, 2019.