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

• Published in: Advances in therapy 2024-08, Vol.41 (8), p.3299-3315
• Main Authors: Patel, Jyoti, Meng, Jie, Le, Hoa, Tanaka, Yoko, Phani, Sudarshan, Salas, Maribel, Wu, Chuntao, Sternberg, David, Esker, Stephen, Anderson, Jeffrey P., Crowley, Aaron, Zhou, Summera Q., Lieb, Camryn, Sun, Haiyan, Doan, Quan V., Santhanagopal, Anu, Reckamp, Karen L.
• Format: Article
• Language: English
• Subjects: Acrylamides - therapeutic use; Adult; Aged; Aged, 80 and over; Aniline Compounds - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Cardiology; Endocrinology; ErbB Receptors - genetics; Female; Humans; Indoles; Internal Medicine; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Original Research; Pharmacology/Toxicology; Pyrimidines; Retrospective Studies; Rheumatology; Treatment Outcome
• ISSN: 0741-238X; 1865-8652; 1865-8652
• DOI: 10.1007/s12325-024-02936-4

Introduction For patients with epidermal growth factor receptor-mutated ( EGFR m) 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 EGFR m 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 EGFR m 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 EGFR m 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.