NEW YORK – The survival benefit from adjuvant treatment with AstraZeneca's PARP inhibitor Lynparza (olaparib) makes it a more cost-effective choice than not giving it at all to patients with early-stage breast cancer harboring germline BRCA1/2 mutations, a study published earlier this month found.
The cost-effectiveness study, published in JAMA Network Open, built on data from more than 1,800 patients enrolled in the Phase III OlympiA trial in which they were randomized to receive either adjuvant Lynparza or placebo for up to one year. Regardless of the arm they were randomized to, all patients underwent regular assessment for breast cancer recurrence based on their medical history, physical examinations, and mammograms or breast MRI.
In 2022, the US Food and Drug Administration approved Lynparza as an adjuvant treatment for early-stage high-risk HER2-negative breast cancer patients who harbored germline BRCA1/2 mutations, had their tumors surgically removed, and had already received chemotherapy. The agency approved the indication based on data from the OlympiA trial showing that Lynparza treatment reduced the risk of death by 32 percent compared to placebo.
The four-year survival rate reported in 2022 was 89.8 percent in the Lynparza arm versus 86.4 percent in the placebo arm. The invasive disease-free survival rate at four years was 82.7 percent for the PARP inhibitor and 75.4 percent for placebo, and distant disease-free survival at four years for Lynparza was 86.5 percent compared to 79.1 percent for placebo, demonstrating an improvement across all survival outcomes with adjuvant Lynparza.
For the cost-effectiveness analysis, researchers led by Elena Elkin, professor of health policy and management at Columbia University Mailman School of Public Health, created a model combining the OlympiA survival data, cost estimates, and estimates of metastatic recurrence from separate studies. They concluded that adjuvant Lynparza resulted in 17.94 life-years and 17.40 quality-adjusted life years (QALYs) at an average cost of $314,789. No adjuvant Lynparza yielded 16.69 life-years and 16.20 QALYs at a cost of $181,655 per year.
Based on this, "adjuvant olaparib was associated with a 1.25-year increase in life expectancy and a 1.20-QALY increase at an incremental cost of $133,133," Elkin and colleagues reported. The incremental cost-effectiveness ratio (ICER) was $106,506 per life-year and $110,962 per QALY gained. At a willingness-to-pay threshold of $150,000 per QALY, an accepted threshold for health gains in the US, adjuvant Lynparza is cost-effective from a healthcare system perspective, they concluded.
"The value of our study is to show that, yes, this drug is expensive, but it actually provides a very good value," said Elkin.
Although insurers are increasingly considering risk-sharing and evidence development contracts with drugmakers for particularly expensive precision medicines — like the new gene therapies for sickle cell disease — in the US, insurance coverage is not explicitly decided based on cost-effectiveness. As such, the findings of this cost-effectiveness study may not directly impact coverage of Lynparza in the adjuvant setting, Elkin said.
However, health authorities in Europe put a lot of stock in cost-effectiveness analyses. For example, the UK's National Institute for Health and Care Excellence initially declined to recommend adjuvant use of Lynparza for this subset of early-stage breast cancer patients but reversed course after it struck a confidential pricing agreement with AstraZeneca that made the treatment cost-effective for routine use for patients in England.
Elkin said her group's analysis was consistent with other cost-effectiveness studies in which the drug also imparted an overall survival benefit, as demonstrated in the OlympiA trial. "In the adjuvant setting, when we see that there is an improvement in overall survival, more often than not, it will also be cost effective," she explained. "The overall survival benefit is really meaningful in this case because the therapy is very well tolerated."
She pointed out that the subpopulation of patients with HER2-negative, germline BRCA1/2-mutant breast cancer also has high-risk disease characteristics. The OlympiA trial also had a large proportion of patients with triple-negative breast cancer, more than 80 percent, which has an especially poor prognosis.
The researchers estimated direct medical costs of Lynparza treatment, routine oncology visits, annual surveillance imaging, and care for metastatic recurrence. In the Lynparza arm, the researchers assumed patients would see their oncologist monthly during the year of treatment, then every six months for five years after completing systemic therapy, and annually after that. Patients not receiving Lynparza were assumed to have an oncologist visit every six months through year five, and annually thereafter. Patients in the study may also have received neoadjuvant or adjuvant chemotherapy.
Elkin and colleagues estimated the monthly cost of Lynparza in 2021, when the analysis was done, to be $14,523. The researchers also estimated the cost of an oncologist visit ($867), the cost of breast MRI and mammogram ($540), and the monthly cost of metastatic breast cancer recurrence ($23,599) using data from previous research and the 2021 Medicare Fee Schedule.
Elkin noted that the cost of testing for germline BRCA1/2 mutations was left out of the cost-effectiveness analysis because her team assumed patients would have known their mutation status by the time they were receiving care. She said her team hopes to explore the value of BRCA1/2 mutation testing and cascade testing for blood relatives in the future.
"There are many other implications of studying [BRCA1/2] testing, [such as] implications for family members and the cascade testing that results once a patient has a positive test or once a mutation is identified in a proband," she said. "Cascade testing and genetic testing has costs, but it also has benefits. In particular with BRCA1/2, we know that there are many risk-reducing actions we can take to prevent breast and ovarian cancer in people with the pathogenic variants."
Now that Lynparza is approved in the adjuvant setting, Elkin and her colleagues noted that real-world use and efficacy of the drug will need to be monitored. As clinical trials are tightly controlled, patients receiving treatment in real-world practice may have slightly different disease profiles than OlympiA participants, which in turn, may yield variable efficacy. Survival outcomes in trials of adjuvant treatments versus in the real world can also be affected by the choice of treatment in later lines, after metastatic disease recurrence. Elkin and her colleagues noted that their and others' cost-effectiveness estimates will need to be updated as more treatments become available for this subset of patients.