EP12.01-64 Metastatic Non-Small Cell Lung Cancer With EGFR Mutations: Treatment Pattern and Outcomes From a Systematic Literature Review

Document Type

Conference Proceeding

Publication Date


Publication Title

J Thorac Oncol


Introduction: The development of targeted therapies for advanced or metastatic NSCLC (mNSCLC) harboring EGFR-activating mutations has benefited patients. However, disease progression is inevitable and subsequent treatment options offer limited clinical benefit. The objective of this systematic literature review was to identify current treatment patterns and outcomes in EGFR-mutated (EGFRm) NSCLC to inform opportunities for future therapeutic development. Methods: This review searched Embase and MEDLINE for publications from 2017-2022 that included adult patients with mNSCLC treated with pharmacotherapy. Supplemental searches included congress abstracts, clinical trial registries, and bibliographies of reviews published between 2020 and 2022. Phase 3 or 4 clinical trials with ≥50 participants and observational studies with ≥200 participants were included without geographic restriction. Evaluation focused on treatment pathways, clinical management, and outcomes. Results: 13,312 records were identified; 130 included data on patients with EGFRm NSCLC. Third-generation (3G) EGFR tyrosine kinase inhibitors (TKIs) demonstrated median progression-free survival (mPFS) of 18.9-20.8 months in randomized controlled trials (RCTs) and 16.8 months in an observational study of osimertinib, both in the 1L setting. Overall survival (OS) was reported at 38.6 months for trials that had mature data. In the post-EGFR TKI setting, platinum-based chemotherapy (PBC) regimens demonstrated mPFS of 4.3-5.4 months in RCTs, with an OS benefit of 15.6 months when adjusted for crossover. Recent studies of immune checkpoint inhibitors (ICIs) in combination with PBC did not demonstrate an improvement over PBC alone (mPFS, 5.6-6.9 months). In later-line studies in the post-EGFR TKI, post-PBC setting, mPFS ranged from 2.7-2.95 months with salvage regimens including pemetrexed, gemcitabine, docetaxel (monotherapy or in combination with bevacizumab), and paclitaxel. The most commonly reported any-grade AEs with 3G EGFR TKIs in the were diarrhea, rash, and paronychia. Commonly reported AEs included nausea, decreased appetite, and anemia with PBC regimens and nausea, fatigue, and peripheral neuropathy with ICI regimens. Conclusions: Treatment options after a 3G EGFR TKI remain limited, with minimal PFS and OS benefits. PBC- and ICI-based regimens have only demonstrated a PFS benefit of ≈5 months. The benefit of salvage regimens is even less, with PFS below 3 months. The poor outcomes seen in published trials and the paucity of current trials in this setting highlight an unmet need for new therapeutic options. [Formula presented] Keywords: Treatment Patterns, Epidermal Growth Factor Receptor Mutations, Metastatic Non-Small Cell Lung Cancer

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Not assigned.





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