Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy

Abstract

Introduction: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3‑DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population.

Methods: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart).

Results: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%.

Conclusion: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

Keywords: Epidermal growth factor receptor mutation; Metastatic non-small cell lung cancer; Osimertinib; Platinum-based chemotherapy; Real-world evidence; Salvage therapies.

Fig. 1

Patient selection diagram and analytic cohorts. AIDS acquired immunodeficiency syndrome, ECOG Eastern Cooperative Oncology Group, EGFR epidermal growth factor receptor, EHR electronic health record, HER3 human epidermal growth factor receptor 3, HIV human immunodeficiency virus, ILD interstitial lung disease, mNSCLC metastatic non-small cell lung cancer, PBC platinum-based chemotherapy, PS propensity score. ^aIndex date was defined as the date of initiation of a new line of therapy after prior treatment with osimertinib and platinum-based chemotherapy. ^bDocumented evidence of an activating EGFR mutation (exon 19 deletion, L858R mutation) or no evidence of other mutations (e.g., BRAF, KRAS, MET, RET, NTRK, ROS1 rearrangement, ALK rearrangement, or EGFR exon 20 mutation). ^cThe exclusion criteria for the matched cohort were based on the entry criteria for the HERTHENA-Lung01 study

Fig. 2

Kaplan–Meier plots of rwPFS (a, c) and rwOS (b, d) in the reference cohort (N = 273; a, b) and the PS-weighted matched subset (ESS = 78; c, d). ESS effective sample size, PS propensity score, rwOS real-world overall survival, rwPFS real-world progression-free survival