Out of pocket costs and patient outcomes in EGFR and ALK positive NSCLC

From the Goulart and Ramsey Group

Patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) derive superior clinical outcomes from oral tyrosine kinase inhibitors (TKIs) compared with other systemic therapies. If patients have insurance plans with high cost-sharing policies for oral drugs, there could be extremely high out of pocket (OOP) TKI prices. In 2011, commercially insured cancer patients paid $198 per month OOP for oral treatments. In 2019, those with Medicare part D paid $7,800 in OOP costs for a 12-month period for TKIs.

The Goulart and Ramsey Groups, from the Hutchinson Institute for Cancer Outcomes Research (HICOR) at the Division of Public Health Sciences, investigated the association of OOP costs for TKIs with overall survival in EGFR and ALK positive advanced NSCLC. Dr. Bernardo Goulart elaborated on the rationale for this study, “Multiple previous studies have shown that patients who incur higher out-of-pocket (OOP) costs for oral cancer medications are at risk of missing doses of medications, or having low adherence to treatment.” They evaluated associations of TKI OOP costs with TKI adherence, duration of therapy (DOT), TKI discontinuation, and overall survival. The Goulart and Ramsey Groups hypothesized that higher OOP costs for TKIs were associated with lower TKI adherence, an increased likelihood of TKI discontinuation and reduced overall survival. This is the first documentation linking higher TKI OOP costs with lower drug adherence and inferior survival outcomes. This study was published in Journal of Clinical Oncology, Oncology Practice.

Patient-level data from the Cancer Surveillance System (CSS) registry that linked insurance claims from Medicare and commercial plans, and pharmacy claims were obtained for patients diagnosed with NSCLC between January 1, 2010 and December 31, 2015. The last follow-up date was on December 31, 2017. Dr. Goulart added, “Our study builds on our in-house developed and validated natural language processing algorithms for identifying patients with EGFR and ALK positive advanced NSCLC. By running the algorithms in the HICOR database, we were able to construe a retrospective cohort of patients with advanced EGFR and ALK positive NSCLC, who are ideal candidates for TKI therapy.” The researchers calculated the patient’s TKI OOP costs by determining the patient’s cost for the prescribed TKI, including the drug deductibles, co-payments, and co-sharing costs. Patients were categorized into monthly TKI OOP cost quartiles. The exposed group was Q4, or the 25% of patients with the highest OOP costs, while the control group consisted of the remaining quartiles, Q1-Q3. Outcomes, including overall survival, TKI adherence, TKI DOT, and TKI discontinuation, were measured from 3 months after TKI initiation to death or censoring.

Graphical Representation of Landmark OS analysis starting at 3 months from TKI initiation, by quartiles of TKI OOP costs.
Landmark OS analysis starting at 3 months from TKI initiation, by quartiles of TKI OOP costs. Image from Dr. Bernardo Goulart

Multivariable cox proportional hazards models were utilized for the association of monthly TKI OOP costs with overall survival and TKI DOT. Multivariable logistic regression models analyzed the associations of TKI OOP costs with TKI adherence and TKI discontinuation. Median monthly TKI OOP costs were $1,431 and $2,888 for Q1-Q3 and Q4, respectively. Patients with the highest TKI OOP costs (Q4) had a higher risk of death than patients in Q1-Q3 (HR=1.85, 95% CI: 1.11-3.10; p=.019). Patients in Q4 had similar TKI DOT than those in Q1-Q3 (HR=1.06, 95% CI:0.53-2.15; p=0.862). Medicare Q4 patients were less likely to be adherent to TKI than Q1-Q3 patients (OR=0.28,95% CI: 0.08-0.91). Q4 and Q1-Q3 patients with commercial insurance had similar TKI adherence (OR=1.30, 95% CI: 0.27-6.16). Q4 Medicare beneficiaries (OR=4.67; 95% CI: 1.38-15.74) and commercially insured patients (OR=2.08; 95% CI: 0.29-14.77) were more likely to discontinue using TKI than Q1-Q3.

Dr. Goulart discussed the study’s finding, “Although our sample sizes were small, our study suggests that patients on Medicare part D are particularly exposed to higher OOP costs for TKIs and [indicates] the financial impact of TKI therapy on drug adherence and survival. The ideal next study should leverage a larger and nationally representative sample of EGFR and ALK positive NSCLC patients enrolled in Medicare part D to verify if our findings are generalizable.” Dr. Goulart added, “In addition, we have engaged in discussions with the GO2 Foundation, a foundation that advocates on behalf of patients with lung cancer, to bring our study findings to the attention of federal policy makers. The goal is to use our scientific evidence as one of the bases for reform of Medicare part D coverage policies for expensive oral oncolytics.”

Dr. Goulart declares, “The study puts in evidence the 2 Elephants in the Room of Financing Cancer Drugs: the flawed insurance policies for oral oncolytics and the exorbitant, unregulated drug prices charged by pharmaceutical companies. Both ultimately result in financial toxicity to our patients, and the latter strains our economy. We hope that federal and state governments will take actions.”

This research was supported by the National Cancer Institute.

Fred Hutch/UW Cancer Consortium members Joseph Unger and Scott Ramsey contributed to this work.

Goulart BH, Unger JM, Chennupati S, Fedorenko CR, Ramsey SD. Out-of-Pocket Costs for Tyrosine Kinase Inhibitors and Patient Outcomes in EGFR-and ALK-Positive Advanced Non–Small-Cell Lung Cancer. JCO Oncology Practice. 2020 Dec:OP-20. DOI: 10.1200/OP.20.00692