Christopher Lemmon, MD, Cleveland Clinic, Cleveland, OH, discusses results from a study on the cost effectiveness of adjuvant osimertinib in resected EGFR mutant non-small cell lung cancer (NSCLC) patients, finding that while it is very expensive, with the right financial incentives in place, it may have the potential to be cost-effective.

This study was presented at the virtual 2021 ASCO Annual Meeting.

Transcript

My name is Chris Lemmon. I'm one of the hematology oncology fellows here at Cleveland Clinic, and I'm excited to share with you our abstract that was presented at ASCO 2021, modeling the cost-effectiveness of adjuvant osimertinib in resected EGFR-mutant non-small cell lung cancer patients.

The reason we did this at last year's ASCO annual meeting, we actually learned that, through the interim analysis of the EDORA Trial, that three years of adjuvant osimertinib provided a significant disease-free survival benefit over placebo in patients with stage Ib to IIIa EGFR-mutant non-small cell lung cancer that was resected.

This interim analysis actually led to FDA approval of osimertinib in the United States and was recently approved actually in Europe as well in this patient population, but this regimen did not come without controversy.

Over the last year or so, there's been a lot of debate about early clinical implementation of this regimen, given the fact that disease-free survival was used as a primary endpoint, the overall immaturity of overall survival data, and just the question of does this really have a significant survival benefit, or just delay recurrence?

Additional questions have come up related to the costs of this treatment as well, since we're exposing a larger population of patients, rather than just the metastatic setting patients to osimertinib, especially when we're not really sure what the magnitude of benefit will be in the final analysis.

However, our patients don't really have a lot of time to just sit around and wait for these data to mature. One of the reasons we wanted to do this study was to at least advance the conversation a little bit and provide at least some more evidence or data for clinicians to have a better discussion with their patient about whether this treatment was going to be beneficial to them.

The aim of our study was to model the EDORA Trial, basically. We modeled based on the interim analysis results of the EDORA Trial and studied the cost-effectiveness of 3 years of adjuvant osimertinib versus placebo in these early stage, resected, EGFR-mutant, non-small cell lung cancer patients.

We used digitized disease-free survival data, curves reproduced from the EDORA Trial, and modeled this and mapped the recurrences within the osimertinib and placebo arms, and divided them between CNS-positive and CNS-negative disease states, due to the recurrence patterns with osimertinib that were seen in EDORA.

Patients could either remain in the no-evidence of disease state after resection and while on osimertinib or placebo, or progress in the CNS, or progress distantly, without CNS disease. At which point, if they did progress to the metastatic state, they would be modeled based on the FLORA Trial of survival curves that use osimertinib in the metastatic setting.

For cost and utility inputs, we use cost inputs from Medicare reimbursement data as well as recent literature and adjusted these for inflation and US dollars. The utility data was derived from recent literature as well, as well as adverse reaction utility data as well.

Due to the overall immaturity of survival data from the EDORA Trial, we did need to make assumptions for overall survival, and made an assumption of an overall survival benefit of five percent for the base case modeling.

We analyzed this further, later in our trial, with sensitivity analyses. For our cost-effectiveness threshold, we set this at $195,000, based on three times the annual GDP per capita in the United States. Like I said, we conducted sensitivity analyses for overall survival, for drug discount costs, and then just to assess our model specifically.

What we found was that the base case incremental cost-effectiveness ratio for 3 years of osimertinib compared to placebo in these early stage, resected, EGFR-mutant, non-small cell lung cancer patients was $317,119.90, compared to placebo.

This did not meet our cost-effectiveness threshold. The costs in the osimertinib arm were significantly higher through the first 3 years of treatment, but then after year 3, costs due to progressive disease were higher in the placebo arm, and they maintained near-equal costs through year 7 into year 10.

However, although the base case did not reach our cost-effectiveness threshold, sensitivity analysis of the incremental benefit in overall survival demonstrated that, if osimertinib does provide an overall survival benefit approximately 25 to 30%, which would correspond to a hazard ratio of 0.75 to 0.7, then this treatment would reach our cost-effectiveness threshold of $195,000.

Additionally, we studied sensitivity analysis of certain increments of the drug discount costs and showed that these discounts can have a significant effect on cost-effectiveness of this regimen, with a 50% drug discount cost reaching cost-effectiveness without any overall survival benefit needed.

Ultimately, these data show that the costs of this treatment is very expensive, but has the potential to be cost-effective if the overall survival data produce a benefit, with a hazard ratio of approximately 0.75 to 0.7, or if there are financial incentives in place, like drug cost-sharing or discounts.

Our study is obviously limited, because we don't have overall survival data from the EDORA Trial that's mature, and we had to make assumptions, due to the modeling of our cost-effectiveness analysis. We're hopeful that these will further the conversation and give clinicians a little bit more information to have discussions with their patients. Thank you.