Assessing Second-Line Treatment Strategies and Outcomes in Epidermal Growth Factor Receptor (EGFR) Oncogene-Driven Stage IV Non-Small Cell Lung Cancer, Following a First-Line EGFR-TKI Therapy.

backgroundOncogene-driven metastatic non-small cell lung cancer (mNSCLC) is associated with poor survival outcomes, despite advancements in first-line tyrosine kinase inhibitor (TKI) therapies.

aimsThis study aimed to characterise second-line treatment strategies for epidermal growth factor receptor (EGFR)-driven mNSCLC, and to evaluate associated clinical outcomes using real-world data. MATERIALS: The EnRICH study prospectively collected clinical data on patients diagnosed with lung cancer from NSW, Australia. Patients with EGFR-driven mNSCLC who received second-line therapy following progression on first-line EGFR-TKI were included in this analysis. Outcomes assessed included progression-free survival (PFS2) and overall survival (OS), measured from second-line treatment.

resultsOf 2000 patients with newly diagnosed lung cancer, between 2016 and 2021, 1720 had NSCLC and 679 had metastatic disease. Among these, 647 underwent molecular testing, with 133 harboring an EGFR mutation. Of these 133, 80 patients received first-line TKI therapy. From this group, 68 who subsequently received second-line treatment following disease progression on first-line TKI were included in this analysis. Of these 68 patients, 77% (n = 52/68) were treated with a first- or second-generation TKI (Erlotinib: n = 39, Gefitinib: n = 7, Afatinib: n = 6) in the first-line setting. The remaining 16 patients received the third-generation TKI Osimertinib. Of the total 68 patients in this cohort, in the second-line setting, 45 patients underwent a change in their systemic therapy, and the remaining 23 patients received radiotherapy either with cessation of first-line TKI (n = 11) or in addition to continuation of first-line TKI (n = 12). Of the 45 patients who underwent a change in their systemic therapy, 32 received systemic therapy alone in the second-line setting and 13 received radiotherapy in addition to a change in systemic therapy. Of these 45 patients, 33 received a TKI, with the majority receiving Osimertinib (n = 28). Median PFS2 was 3.0 months (95% CI: 1.32-5.49), with no significant difference between patients treated with second-line TKI and those receiving other therapies (p = 0.24). Median OS was 15.0 months (95% CI: 13.24-23.66) and similarly did not differ significantly between second-line TKI and alternative treatment strategies (p = 0.17).

conclusionsUsing real-world data from EnRICH, this represents the largest retrospective analysis of this cohort in Australia and largely predates first-line Osimertinib use. Findings reveal a trend toward second-line Osimertinib use, even after first-line TKI, without significant differences in survival. There, however, remains significant heterogeneity in approaches. The lack of robust second-line data, however, highlights the need for investigating novel therapeutic approaches.