Lynparza approved in China as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer
AstraZeneca and MSD’s Lynparza (olaparib) has been approved in China 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 1st-line platinum-based chemotherapy in combination with bevacizumab, and whose cancer is associated with homologous recombination deficiency (HRD)-positive status
In China, ovarian cancer is the third most common gynaecologic cancer, with a five-year survival rate of approximately 39%, largely because more than 70% of women are diagnosed with advanced disease (Stage III or IV). In 2020, there were over 55,000 new cases of ovarian cancer in China.
The approval by China's National Medical Products Administration was based on an HRD-positive subgroup exploratory analysis of the PAOLA-1 Phase III trial which showed Lynparza plus bevacizumab demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone for patients with HRD-positive advanced ovarian cancer. During European Society for Medical Oncology Congress (ESMO) 2022, the final overall survival (OS) results were presented from the PAOLA-1 Phase III trial demonstrating that Lynparza plus bevacizumab provided a clinically meaningful improvement in overall survival in HRD-positive advanced ovarian cancer.
Professor Ding Ma, Member of the Chinese Academy of Engineering, said: “Ovarian cancer has the highest fatality rate among gynaecologic cancers in China. The emergence of PARP inhibitors and their application in the 1st-line treatment of ovarian cancer could help patients delay disease progression and achieve long-term remission. In the PAOLA-1 trial, the combination of olaparib and bevacizumab demonstrated clinically meaningful improvements in overall survival. This approval provides HRD-positive patients with a new option for 1st-line maintenance therapy.”
The initial results from the PAOLA-1 Phase III trial showed that Lynparza plus bevacizumab reduced the risk of disease progression or death by 67% in the subgroup of patients with HRD-positive advanced ovarian cancer (based on a hazard ratio [HR] of 0.33; 95% confidence interval [CI] 0.25-0.45 from the pre-specified exploratory analysis). The primary endpoint in the intent-to-treat population was a statistically significant and clinically meaningful improvement in PFS. The data from the PAOLA-1 trial was published in The New England Journal of Medicine in 2019.
Further results from the five-year analysis of the PAOLA-1 trial recently presented at the ESMO 2022 showed Lynparza plus bevacizumab increased median overall survival to 56.5 months versus 51.6 months with bevacizumab alone, in patients with newly diagnosed advanced ovarian cancer irrespective of HRD status. This increase was not statistically significant. In HRD-positive patients, Lynparza plus bevacizumab provided a clinically meaningful improvement in overall survival, reducing the risk of death by 38% versus bevacizumab (based on a HR of 0.62; 95% CI 0.45-0.85 from the pre-specified exploratory sub-group analysis) despite PAOLA-1 having 30% Stage IV patients. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials, with no new safety signals.
Related news and insights
In a 14 to 2 vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted that the benefit-risk profile of melphalan flufenamide (Pepaxto) is not favorable for the approved indicated population of patients with relapsed/refractory multiple myeloma
In an 8 to 4 vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted that the final overall survival (OS) data submitted did not demonstrate a strong enough benefit-risk ratio to support the continued approval of duvelisib (Copiktra) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least 2 prior therapies