Adherence and Persistence To Oral Targeted Therapies for Non-Small-Cell Lung Cancer and Association With Survival Outcomes

OBJECTIVES: Since the early 2000s, several oral targeted therapies (OTTs) have been approved by the FDA for the treatment of non-small-cell lung cancer (NSCLC). OTTs have the advantage of avoiding injection site adverse effects but require more frequent dosing, making adherence a potential issue. The study aimed to compare adherence to and persistence for OTTs that target ALK and EGFR as well as their association with survival outcomes.

METHODS: This was a retrospective cohort study utilizing 2006-2019 SEER-Medicare data of patients with NSCLC aged ≥66 years receiving ALK inhibitor (ALKi: Alectinib, Brigatinib, or Crizotinib) or EGFR inhibitor (EGFRi: Afatinib, Erlotinib, or Gefitinib). Patients were followed from treatment commencement until death, loss to follow-up, or end of study. Descriptive statistics were used to summarize data. Cox regression were used to determine the association of OTT class, adherence, and persistence with progression-free survival (PFS) and overall survival (OS). Covariates included age, gender, race/ethnicity, comorbidity score, time to treatment, and year of diagnosis.

RESULTS: Compared to EGFR group, the ALK group were younger and more likely to be White (76.4% vs 69.3%, p<0.001). Adherence (59.2%±34.2% vs 51.3%±34.8%, p<0.0001) and persistence (302 days (IQR=95-365 days) vs 182 days (IQR=65-365 days, p<0.0001) was higher in the ALK group.

The ALK group had better overall survival (AHR=0.67, 95% CI=0.58-0.76, p<0.0001). Higher adherence was associated with better PFS (AHR=0.99, 95% CI=0.99-0.99, p<0.0001) and OS (AHR=0.99, 95% CI=0.98-0.99, p<0.0001). Better PFS (0.997, 95% CI=0.997-0.998, p<0.0001) and OS (AHR=0.996, 95% CI=0.996-0.996, p<0.0001) were also observed with higher persistence. Sensitivity analyses with follow-up starting one year after treatment commencement showed similar findings.

CONCLUSIONS: Adherence was higher for patients receiving ALKi vs EGFRi, which was associated with better OS. Prioritizing the prescription of this newer class of OTTs might improve cancer outcomes for patients with lung cancer.