Tyrosine kinase inhibitors have changed the paradigm of care for advanced EGFR- and ALK-positive non–small cell lung cancer (NSCLC), but not all patients taking these drugs may receive the same benefit. The results of a recent retrospective analysis suggest that higher out-of-pocket costs for tyrosine kinase inhibitors may be associated with significantly shorter overall survival.

According to data presented at the 2019 ASCO Quality Care Symposium,¹ in patients with advanced EGFR- or ALK-positive NSCLC, the highest quartile of tyrosine kinase inhibitor out-of-pocket costs was associated with an increased risk of death, shorter duration of tyrosine kinase inhibitor therapy, and a lower number of prescriptions.

Bernardo H.L. Goulart, MD

“There are several possible explanations for the associations of cost on survival, including decreased access to tyrosine kinase inhibitors and a higher likelihood of discontinuance, decreased ability to afford other elements of health care, or decreased ability to afford nonmedical needs such as food and clothing,” said lead author of the study, Bernardo H.L. Goulart, MD, Associate Professor of Medicine and Oncology at the University of Washington School of Medicine and Assistant Member of Public Health Sciences Research at Fred Hutchinson Cancer Research Center, Seattle. “We need a confirmatory study using a larger and nationally representative sample. However, if confirmed, our results may support changes in coverage policies for oral tyrosine kinase inhibitors, at least for patients with mutation-positive NSCLC.”

As Dr. Goulart explained, although tyrosine kinase inhibitors have become standard first-line therapy for patients with advanced NSCLC harboring EGFR mutations or ALK-gene rearrangements, they are expensive medications, costing thousands of dollars per month. What’s more, he added, both commercially and Medicare-insured patients are bearing higher proportions of these costs.

“We are all too aware of the detrimental impacts of financial toxicity on patient outcomes,” observed Dr. Goulart. “Many patients with cancer are forced to file for bankruptcy and/or discontinue therapy, and we know that financial distress is correlated with negative quality-of-life scores.”

Retrospective Study Design

For this retrospective cohort study, Dr. Goulart and colleagues sought to test the association of high out-of-pocket tyrosine kinase inhibitor costs on overall survival, medication-possession ratio, and duration of therapy in patients with EGFR- and ALK-positive stage IV NSCLC. The researchers identified patients with EGFR-positive and ALK-positive advanced NSCLC, diagnosed between 2010 and 2015, in the Hutchinson Institute for Cancer Outcomes Research (HICOR) registry-claims database. All patients had at least one pharmacy claim for EGFR or ALK tyrosine kinase inhibitors, continuous insurance enrollments, and a minimal survival of 90 days from the start of oral tyrosine kinase inhibitor therapy.

If confirmed, our results may support changes in coverage policies for oral tyrosine kinase inhibitors, at least for patients with mutation-positive NSCLC.

— Bernardo H.L. Goulart, MD

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Researchers calculated the average monthly patient out-of-pocket costs for the first 3 months of tyrosine kinase inhibitor therapy by subtracting the amount reimbursed from the maximum amount allowed by insurance for a 30-day tyrosine kinase inhibitor supply. Patients were then categorized into quartiles based on the average monthly medication costs, which were adjusted for 2017 dollars. The study’s primary outcome was overall survival, with researchers using a landmark survival analysis with multivariate Cox regression to test its association with monthly out-of-pocket costs in the first 3 months of tyrosine kinase inhibitor therapy.

Out-of-Pocket Costs and Survival

After applying the multiple inclusion and exclusion criteria, researchers identified 105 patients who constituted the final eligible cohort. As Dr. Goulart reported, patients with the highest monthly medication costs (n = 27) were older on average and resided in areas of lower household income and higher material deprivation. They were also more likely to have Medicare insurance and low-income–subsidy eligibility. In addition, he noted, patients in the highest quartile of cost were less likely to receive chemotherapy or immunotherapy, and the time it took from diagnosis to the start of tyrosine kinase inhibitor therapy was slightly longer in this group of patients than in their peers.

The median monthly tyrosine kinase inhibitor cost was approximately $1,400 for the first three quartiles but doubled to more than $2,800 per month for the last quartile of patients, reported Dr. Goulart. However, these increased costs affected more than patients’ bank accounts. The median overall survival was 22.3 months for the patients in the first three quartiles, compared with 9.1 months in the highest quartile of cost (unadjusted hazard ratio [HR] = 1.66).

“A multivariate Cox proportional hazard model shows that the patients in the highest quartile of cost were 2.31 times as likely to die at any point in time compared with their peers, a result that was statistically significant,” announced Dr. Goulart.

When stratified by insurance type at initiation of therapy, the difference was even more pronounced for patients with Medicare. For the 70 Medicare beneficiaries, the median overall survival was 24 months in the first three quartiles, vs 6.2 months in the highest quartile of tyrosine kinase inhibitor out-of-pocket costs (unadjusted HR = 1.98). Of note, said Dr. Goulart, the association between cost and survival did not hold for the 35 commercially insured patients.

High out-of-pocket costs were also associated with a decreased probability of remaining on tyrosine kinase inhibitor therapy. In the first three quartiles, the median duration of first tyrosine kinase inhibitor therapy lasted 8 months compared with 4 months for patients in the highest quartile. A multivariate Cox model found that patients in the highest quartile were 2.25 times as likely to discontinue tyrosine kinase inhibitor therapy at any point in time compared with their peers, Dr. Goulart said.

Finally, the medication-possession ratio characterizing prescriptions of tyrosine kinase inhibitors, was higher in the first three quartiles of patients at 1.21 compared with 1.06 for patients in the highest quartile, a result that was statistically significant after adjustment for multiple patient characteristics.

Dr. Goulart acknowledged several limitations to the study, including its small sample size and selection bias inherent in the retrospective design. In addition, he noted, because out-of-pocket costs were estimated from pharmacy claims, researchers could not account for financial assistance programs, although eligibility for low-income subsidy was included in the analysis. Researchers were also unable to distinguish between the effects of the tyrosine kinase inhibitor–specific costs from other high health-care costs for patients in the highest quartile, Dr. Goulart concluded. ■

DISCLOSURE: This research was sponsored by the National Institutes of Health. Dr. Goulart has received travel funding from Flatiron Health.

REFERENCE

1. Goulart BHL, et al: Effect of high patient out-of-pocket cost for oral tyrosine kinase inhibitors on survival in EGFR and ALK positive stage IV non-small cell lung cancer. 2019 ASCO Quality Care Symposium. Abstract 3. Presented September 7, 2019.