NEW YORK – The National Institute for Health and Care Excellence in the UK has recommended AstraZeneca's PARP inhibitor Lynparza (olaparib) with the antiangiogenic drug bevacizumab as a maintenance treatment for certain previously treated patients with homologous recombination repair deficient ovarian cancers.
On Friday, NICE issued a final draft guidance recommending that the National Health Service provide Lynparza and bevacizumab as a maintenance treatment to patients with stage 3 or 4 high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients must have completely or partially responded to first-line platinum-based chemotherapy with bevacizumab, which is sold by Genentech under the brand name Avastin and is available as a biosimilar. Patients' cancers must have homologous recombination deficiency, defined as harboring a BRCA1/2 mutation or genomic instability.
In 2021, NICE agreed to make the regimen available to patients in England through a managed access agreement under the Cancer Drugs Fund, which allowed the sponsor to collect further real-world evidence from the population, and within the PAOLA-1 study comparing Lynparza-bevacizumab against bevacizumab.
The US Food and Drug Administration approved this same ovarian cancer indication of Lynparza-bevacizumab in 2020 based on progression-free survival data from PAOLA-1. At the time, the agency also approved Myriad's myChoice CDx to identify patients with homologous recombination repair deficiency who are eligible for treatment.
Later, that trial also showed an overall survival advantage with Lynparza-bevacizumab compared to just bevacizumab in all ovarian cancer patients in the trial. However, the survival benefit was more pronounced among those with homologous recombination repair deficiency, and there no overall survival advantage seen with the addition of Lynparza in those without this biomarker.
Despite this data, NICE issued a draft decision in July declining to recommend the regimen for routine use within the NHS. At the time, NICE said that while new clinical trial data show that people taking Lynparza-bevacizumab have longer progression-free and overall survival compared to those on just bevacizumab, "the economic evidence is very uncertain."
In the latest final draft guidance, though, NICE appears to be swayed on the regimen's efficacy and cost-effectiveness after having reviewed the totality of evidence, including data collected within the managed access program. "The most likely cost-effectiveness estimates for olaparib with bevacizumab are within what NICE considers an acceptable use of NHS resources," the organization said. "So, it is recommended for routine use in the NHS."
The list price for Lynparza is £2,317.50 ($2,902.32) for each 14-day pack or £4,635.00 for a 28-day cycle, but AstraZeneca has a commercial arrangement that makes Lynparza and bevacizumab available to the NHS at an undisclosed discount.
David Brocklehurst, head of oncology at AstraZeneca UK, estimated that around 50 percent of women in the UK with advanced ovarian cancer have tumors that are homologous recombinant repair deficient, and said in a statement that "it is critical" for NHS to provide routine testing to increase patients' chances of getting this treatment.
While Myriad's myChoice CDx was used to determine ovarian cancer patients' homologous recombination repair deficiency status in PAOLA-1, NHS England's Genomic Laboratory Hubs will likely be conducting HRD testing for patients in this setting "within the next few months," according to information in NICE's final draft guidance.