EGFR tyrosine kinase inhibitor combined with concurrent or sequential chemotherapy for patients with advanced lung cancer and gradual progression after first-line EGFR-TKI therapy: A randomized controlled study

Abstract Introduction According to previous reports, continuing TKI therapy may be beneficial when patients with non-small cell lung cancer (NSCLC) and EGFR mutations gradually progress after initial EGFR tyrosine-kinase inhibitor (TKI) treatment. We aimed to compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential treatment after patients gradually progressed from first-line EGFR-TKI treatment. Methods Patients who had gradual progression and were EGFR-T790M mutation–negative were randomly divided into two groups. In the concurrent group, patients were treated with pemetrexed plus cisplatin along with the same EGFR-TKI. In the sequential group, patients continued with EGFR-TKI until the disease progressed again, according to the RECIST criteria, and then switched to chemotherapy. We evaluated the patients’ progression-free survival (PFS) and overall survival (OS) time. Results Ninety-nine patients were enrolled: 49 in concurrent group and 50 in sequential group. The median PFS was 7.7 months (95% CI, 3.6–11.7) in concurrent group and 5.7 months (95% CI, 3.5–7.9) in sequential group (HR = 0.66; 95% CI, 0.44–1.00; p = 0.026), respectively. For sequential group, the mPFS1 and mPFS2 were 1.8 months (95% CI, 1.4–2.3) and 3.8 months (95% CI, 3.1–4.5), respectively. The median OS of concurrent group was longer than that of sequential group (20.0 vs. 14.7 months; HR = 0.52, 95% CI: 0.32–0.85; p = 0.038). Conclusions This study suggests that for patients with advanced NSCLC and gradual progression who are EGFR-T790M mutation–negative after initial EGFR-TKI therapy, EGFR-TKI combined with chemotherapy confers longer PFS and OS than sequential EGFR-TKI and chemotherapy does.