AstraZeneca’s and Merck’s Olaparib, Lynparza has been approved in US as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer, the companies said Monday in a press release.
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US (Merck: known as MSD outside the US and Canada) today announced LYNPARZA® (olaparib) in combination with bevacizumab has been approved in the US for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. Patients will be selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
The approval by the US Food and Drug Administration (FDA) was based on a biomarker subgroup analysis from the Phase III PAOLA-1 trial which showed LYNPARZA in combination with bevacizumab reduced the risk of disease progression or death by 67% (equal to a hazard ratio of 0.33). The addition of LYNPARZA also improved progression-free survival (PFS) to a median of 37.2 months versus 17.7 months with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.
Approximately one in two women with advanced ovarian cancer has an HRD-positive tumor. For patients with advanced ovarian cancer, the primary aim of 1st-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission.
Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial and medical oncologist, Centre Léon Bérard and President of the GINECO group, said: “Ovarian cancer is a devastating disease. The magnitude of benefit in HRD-positive patients in the PAOLA-1 trial is impactful. The combination of LYNPARZA and bevacizumab now provides women with HRD-positive advanced ovarian cancer with a new standard of care and I look forward to seeing this translate into clinical practice.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “This approval represents another milestone for LYNPARZA in patients with ovarian cancer. The median progression-free survival of more than three years offers new hope for more women to delay relapse in this difficult-to-treat disease. These results further establish that HRD-positive is a distinct subset of ovarian cancer, and HRD testing is now a critical component for the diagnosis and tailoring of treatment for women with advanced ovarian cancer.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, said: “Advances in understanding the role of biomarkers and PARP inhibition have fundamentally changed how physicians treat this aggressive type of cancer. Today’s approval based on the PAOLA-1 trial highlights the importance of HRD testing at diagnosis to identify those who may benefit from LYNPARZA in combination with bevacizumab as a 1st-line maintenance treatment.”
Fatal adverse reactions occurred in 1 patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received LYNPARZA/bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).
The most common adverse reactions (Grades 1-4) occurring in ≥10% of patients treated with LYNPARZA/bevacizumab and at ≥5% frequency compared to placebo/bevacizumab were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).
In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).