Olaparib Approved in the US as a First-Line Maintenance Treatment of Germline BRCA-mutated Metastatic Pancreatic Cancer

The country was saddened to learn over the weekend that Rep. John Lewis (D-Ga.), the legendary Civil Rights activist, was being treated for stage four pancreatic cancer.

“While I am clear-eyed about the prognosis, doctors have told me that recent medical advances have made this type of cancer treatable in many cases, that treatment options are no longer as debilitating as they once were, and that I have a fighting chance,” Lewis says in a statement.

One of those medical advances was announced today, as the FDA approved olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. AstraZeneca and Merck are marketing this new drug as LYNPARZA. Patients will be selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

The approval follows the recommendation by the U.S. FDA Oncologic Drugs Advisory Committee on Dec. 17 for LYNPARZA in this indication and was based on results from the pivotal Phase 3 POLO trial published in the New England Journal of Medicine and presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) where LYNPARZA nearly doubled the time patients with gBRCAm metastatic pancreatic cancer lived without disease progression or death to a median of 7.4 months vs. 3.8 months on placebo (HR 0.53 [95% CI 0.35-0.81] p=0.0035).

The most common adverse reactions (ARs) ≥10% were fatigue/asthenia (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%). The most common ≥ grade 3 ARs were anemia (11%), fatigue/asthenia (5%), decreased appetite (3%), abdominal pain (2%), vomiting (1%) and arthralgia (1%). Among patients taking LYNPARZA, dose interruptions due to an adverse reaction of any grade occurred in 35% and dose reductions due to an adverse reaction occurred in 17%. Discontinuation due to adverse reactions occurred in 6% of patients receiving LYNPARZA.

Dave Fredrickson, executive vice president, head of the oncology business unit, AstraZeneca, says, “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. LYNPARZA is now the only approved targeted medicine in biomarker-selected patients with advanced pancreatic cancer.”

Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, says, “LYNPARZA embodies Merck’s and AstraZeneca’s commitment to advance the treatment of challenging types of cancer, including metastatic pancreatic cancer. The expanded approval of LYNPARZA represents a significant milestone for patients and supports the value of germline BRCA testing in patients with this disease.”

Hedy L. Kindler, MD, co-principal investigator of the POLO trial and professor of medicine, University of Chicago Medicine, says, “Today’s approval of olaparib based on the POLO results gives clinicians an important first-line maintenance treatment option which nearly doubled the progression-free survival benefit in patients with germline BRCA-mutated metastatic pancreatic cancer.”

Julie Fleshman, president and CEO, Pancreatic Cancer Action Network, says, “Metastatic pancreatic cancer patients have been waiting a long time for new therapy options for their devastating disease. Today’s approval of LYNPARZA provides an exciting new treatment option for patients with germline BRCA-mutated metastatic pancreatic cancer.”

The Pancreatic Cancer Action Network (PanCAN) is a U.S.-based organization that supports and advocates on behalf of the patients, caregivers and communities affected by pancreatic cancer.

LYNPARZA is currently approved in 65 countries for the maintenance treatment of platinum-sensitive relapsed ovarian cancer, regardless of BRCA status. It is approved in the U.S., the EU, Japan and several other countries as first-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 44 countries, including the U.S. and Japan, for gBRCAm, HER2-negative metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer.