Real-world outcomes among patients with EGFR-mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors versus immunotherapy or chemotherapy in the first-line setting

Background: Despite national guideline recommendations, epidermal growth factor receptor mutated (EGFRm) metastatic non-small cell lung cancer (mNSCLC) patients may still receive suboptimal treatment in the first line (1L). This study evaluated 1L therapy initiation in relation to biomarker testing results and time to next-treatment or death (TTNTD) in patients receiving EGFR tyrosine kinase inhibitors (TKIs) versus immunotherapy (IO) or chemotherapy. Methods: Stage IV EGFRm mNSCLC adults that initiated 1L EGFR TKI (first, second, or third generation), IO +/- chemotherapy (IO users), or chemotherapy alone from 5/2017-12/2019 were identified from the Flatiron database. Logistic regression estimated the likelihood of initiating treatment before receiving testing results for each therapy. Median TTNTD was evaluated via Kaplan-Meier analysis. Adjusted hazards ratios (HRs) and 95% CI examining the association of 1L therapy with TTNTD were reported from multivariable Cox proportional-hazards models. Results: Among 758 EGFRm mNSCLC patients, EGFR TKI was used as 1L therapy for 87.3% of patients (n = 662), IO in 8.3% (n = 63), and chemotherapy only in 4.4% (n = 33). The majority of IO (61.9%) and chemotherapy only patients (60.6%) initiated therapy before test results were available, compared to 9.7% of EGFR TKIs. The odds of initiating therapy before receiving test results were higher for IO (OR: 19.6, p < 0.001) and chemotherapy alone (OR: 14.1, p < 0.001) in comparison to EGFR TKIs. Compared to IO and chemotherapy, EGFR TKIs had longer median TTNTD (EGFR TKI: 14.8 months, 95% CI: 13.5-16.3; IO: 3.7 months, 95% CI 2.8-6.2; chemotherapy: 4.4 months, 95% CI 3.1-6.8, p < 0.001). EGFR TKI patients had significantly lower risk of initiating second--line therapy or death compared to patients on 1L IO (HR: 0.33, p < 0.001) or 1L chemotherapy (HR: 0.34, p < 0.001). Conclusions: A portion of biomarker testing results were not used to guide 1L therapy. Patients initiating EGFR TKI as 1L therapy had longer TTNTD than IO or chemotherapy.