Out-of-Pocket Costs for Tyrosine Kinase Inhibitors and Patient Outcomes in EGFR - and ALK -Positive Advanced Non–Small-Cell Lung Cancer

Abstract

QUESTIONS ASKED: What is the impact of higher patient out-of-pocket (OOP) costs for oral tyrosine kinase inhibitors (TKIs) on the survival and TKI adherence in advanced epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC)? SUMMARY ANSWER: The highest quartile of patient TKI OOP costs was associated with a relative increase of 85% in the risk of death, with an absolute decrease of 32.1% in TKI adherence, and with an absolute increase of 37.9% in the risk of discontinuation of TKIs in the first 3 months of TKI therapy. WHAT WE DID: We identified patients diagnosed with EGFR-and ALK-positive stage IV NSCLC between Jan-uary 1, 2010, and December 31, 2015, in the Cancer Surveillance System tumor registry and linked their records to medical and pharmacy claims from Medicare and two commercial insurance plans (Premera Blue Cross and Regence Blue Shield). From pharmacy claims, we estimated patients' average monthly OOP costs for EGFR and ALK TKIs over the first 3 months of TKI therapy. We categorized patients into quartiles of average monthly TKI OOP costs (Q1 , Q2 , Q3 , Q4). Since we were interested in the effects of higher TKI OOP costs on patient outcomes, we defined Q1-3 quartiles as controls and Q4 as the exposed group. The primary outcome measure was overall survival (OS). Secondary outcomes included TKI adherence, TKI duration of therapy (DOT), and TKI early discontinuation within 3 months. We used landmark analysis starting at 3 months from TKI initiation and employed Cox and logistic multivariate regression models to test associations while accounting for confounding patient characteristics. WHAT WE FOUND: A total of 105 patients were eligible. The median average monthly TKI OOP costs were $1,431 and $2,888 for the Q1-3 (n 5 78) versus Q4 (n 5 27) groups, respectively. Compared with Q1-3, Q4 patients had an increased risk of death (median OS 22.4 v 9.1 months; adjusted hazard ratio [HR], 1.85; 95% CI, 1.11 to 3.10; P 5 .019), decreased TKI adherence (65.4% v 33.3%; adjusted odds ratio [OR], 0.28; 95% CI, 0.10 to 0.76; P 5 .012), and higher risk of discontinuing TKIs within 3 months (10.3% v 48.2%; adjusted OR, 8.75; 95% CI, 2.59 to 29.52; P , .001). These associations remained statistically significant after accounting for multiple patient confounding characteristics. TKI DOT did not statistically differ between Q1-3 and Q4 groups (adjusted HR, 1.06; 95% CI, 0.53 to 2.15; P 5 .862). BIAS, CONFOUNDING FACTORS, AND DRAWBACKS: Despite the use of multivariate regression analyses, our results are still subject to selection bias given the observational study design. The use of pharmacy claims serves only as an approximation of TKI OOP costs and TKI adherence because claims do not account for access to drug financial assistance programs and do not provide the actual reasons for TKI discontinuation (eg, tumor progression v drug intolerance v financial burden). Our sample size was small and restricted to the Wash-ington State, limiting the generalizability of our findings. REAL-LIFE IMPLICATIONS: Higher out-of-pocket costs for TKIs are associated with decreased TKI adherence, increased risk of early TKI discontinuation, and inferior OS in patients with EGFR-and ALK-positive advanced NSCLC. Our findings suggest that patients with NSCLC who are eligible for targeted therapies are at risk of substantial financial toxicity when faced with higher TKI OOP costs. If confirmed in nationally representative studies, our results should support changes to coverage policies for TKIs. abstract PURPOSE We investigated the association of out-of-pocket (OOP) costs for tyrosine kinase inhibitors (TKIs) with overall survival (OS) in epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We secondarily investigated associations of TKI OOP costs with TKI adherence, duration of therapy (DOT), and TKI discontinuation. METHODS We used the Hutchinson Institute for Cancer Outcomes Research registry-claims database to identify patients with stage IV EGFR-or ALK-positive NSCLC; $ 1 claims for EGFR or ALK TKIs; and $ 3-month survival from TKI initiation. We estimated the average monthly TKI OOP costs per patient up to 3 months from TKI initiation, categorizing patients into quartiles of TKI OOP costs (Q1 , Q2 , Q3 , Q4). We conducted landmark analysis at 3 months from TKI initiation to compare Q1-3 v Q4 TKI OOP costs with respect to OS, TKI DOT, TKI adherence, and TKI discontinuation. RESULTS Seventy-eight and twenty-seven patients comprised the Q1-3 and Q4 groups, respectively. Median monthly TKI OOP costs were $1,431 (Q1-3) v $2,888 (Q4). Compared with Q1-3, Q4 patients had inferior OS (adjusted hazard ratio [HR], 1.85; [95% CI, 1.11 to 3.10], similar TKI DOT (adjusted HR, 1.06; 95% CI, 0.53 to 2.15), decreased TKI adherence (adjusted odds ratio [OR], 0.28; 95% CI, 0.10 to 0.76), and higher TKI discontinuation rate (adjusted OR, 8.75; 95% CI, 2.59 to 29.52). CONCLUSION Among patients with advanced EGFR-and ALK-positive NSCLC, higher TKI OOP costs are associated with decreased TKI adherence, a higher likelihood of TKI discontinuation, and inferior survival.