Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib

For patients with advanced epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) who progress on first-line osimertinib, the optimal second-line treatment regimen after progression is not known. We sought to assess practice patterns and evaluate the association between different therapies and survival in patients with EGFR-mutated NSCLC following progression on first-line osimertinib. Retrospective cohort study of patients who received first-line treatment with osimertinib using a population-based, multicenter nationwide electronic health record-derived deidentified database. We identified 2373 patients who received first-line osimertinib. The majority (n = 2279) received osimertinib monotherapy. A total of 538 patients received first-line osimertinib and had second-line treatment data available. Second-line treatment regimens were varied: 65% (n = 348) included chemotherapy, 37% (n = 197) included an immune checkpoint inhibitor (ICI), and 44% (n = 234) included an EGFR tyrosine kinase inhibitor (TKI). We then analyzed the 333 patients with performance status 0-2 who received chemotherapy with osimertinib (n = 107, 32%) versus chemotherapy without osimertinib (n = 226, 68%). The continuation of osimertinib with chemotherapy was associated with superior progression-free survival (PFS; median: 10.1 versus 5.9 months, Hazard Ratio [HR]: 0.48, 95% Confidence Interval [CI]: [0.34, 0.68], P < .001) and overall survival (OS; median: 17.0 versus 12.8 months, HR: 0.64, 95% CI: [0.44, 0.93], P = .018) compared to other chemotherapy approaches without osimertinib. This effect was most pronounced in patients with an EGFR exon 19 deletion. Following progression on osimertinib, a wide variety of treatment regimens were used. The continuation of osimertinib with chemotherapy in the second line was associated with increased PFS and OS. Following progression on osimertinib, patients with EGFR-mutated NSCLC have many treatment options available. In a retrospective cohort study, we found that continuing osimertinib with chemotherapy was associated with prolonged survival versus patients who did not continue targeted therapy. This has important treatment implications for the many patients with metastatic EGFR-driven NSCLC who will inevitably progress on first-line therapy.