Olaparib in BRCA+ Pancreatic Cancer:
Cost-effectiveness Analyzed 

Roxanne Nelson, RN, BSN

November 19, 2020

The PARP inhibitor olaparib (Lynparza) has been shown to delay progression  in patients with metastatic pancreatic cancer who harbor BRCA 1/2 mutations, and is now approved for this indication.

A new study suggests that this approach can be cost-effective in certain cases, but an expert not involved in the research was not convinced.

The study was published this month in JNCCN: Journal of the National Comprehensive Cancer Network.

The researchers calculated the incremental cost-utility ratios (ICUR) for patients who were receiving maintenance olaparib as compared with placebo. The medical costs in their analysis included drug acquisition and costs attributed to health states, for managing adverse effects, and for end-of-life care. The modeling suggested that maintenance olaparib would be cost-effective for certain patient subgroups and settings, when using a threshold of $200,000 per quality-adjusted life-year (QALY).

The "cost-effectiveness of olaparib as measured by cost-per-QALY is reasonably close to the commonly used willingness-to-pay thresholds," coauthor Bin Wu, PhD, of Shanghai Jiaotong University, Shanghai, China, commented in a statement.

"The value of olaparib maintenance would be even more attractive if the price were lower," he added.   

Small Proportion of Patients

About 6%–8% of patients with pancreatic cancer harbor pathogenic BRCA or PALB2 mutations.

Olarparib was approved last year for use as a first-line maintenance treatment of germline BRCA-mutated metastatic pancreatic cancer, based on findings from the pivotal POLO trial. The results showed that median progression-free survival was nearly doubled with olaparib compared with placebo (7.4 months vs 3.8 months; hazard ratio, 0.53; P = .004), but there was no overall survival benefit.

Olaparib effect of delaying disease progression was a major driver of economic outcomes, but there was no overall survival benefit with maintenance treatment. "The benefit of overall survival is not conclusive as a major driver of economic evaluation," said study coauthor Lizheng Shi, PhD, MsPharm, director of the Health Systems Analytics Research Center at Tulane University in New Orleans, Louisiana.

Improved patient selection for maintenance olaparib or reduced drug costs may both be necessary to establish olaparib as a cost-effective therapy in metastatic pancreatic cancer, he told Medscape Medical News. "However, improving patient selection may be more practical."

An expert not involved in the study echoed these comments, and was not convinced by the new analysis. "While there is emerging evidence that precision medicine is relevant to subsets of patients with advanced pancreatic cancer, definitive results to support the cost-effectiveness of maintenance olaparib is lacking," commented Robert A. Wolff, MD, University of Texas MD Anderson Cancer Center, Houston, in a statement.

He also noted that "cost-effectiveness analyses of PARP inhibitors used in similar patient populations with recurrent ovarian cancer have been negative."  

Study Details

For their study, the researchers created a hypothetical target population comprised of patients with metastatic pancreatic cancer with a germline BRCA1 or BRCA2 mutation, who had not progressed during first-line platinum-based chemotherapy, according to the patient characteristics of the POLO trial.

Efficacy and toxicity data were also obtained from the POLO trial, whereas cost and health preference data were drawn from the literature.

The team then analyzed the incremental cost-utility ratio, incremental net-health benefit, and incremental monetary benefit.

The results of their modeling showed that maintenance olaparib had an incremental cost-utility ratio of $191,596 per additional progression-free survival QALY gained, with a high cost of $132,287 and 0.691 QALY gained, vs results for a placebo.

Subgroup analysis showed that maintenance olaparib had at least a 16.8% probability of cost-effectiveness at the threshold of $200,000/QALY, but these results were sensitive to both the hazard ratio of progression free survival and the cost of olaparib.

When they took overall survival into account, maintenance olaparib had an incremental cost-utility ratio of $265,290 per additional QALY gained, with a high cost of $128,266 and 0.483 QALY gained, vs placebo.

The study had no specific funding. Wu and Shi have disclosed no relevant financial relationships.

J Natl Compr Canc Netw. Published online November 2, 2020. Full text

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