Totality outcome of afatinib sequential treatment in patients with EGFR mutation-positive non-small cell lung cancer in South Korea (TOAST): Korean Cancer Study Group (KCSG) LU-19-22

Abstract

Background Irrespective of the first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor chosen, acquired resistance to therapy is inevitable. Therefore, a key consideration when assessing therapeutic choices is the availability of subsequent treatment options following disease progression. We assessed clinical outcomes in patients who received first-line afatinib treatment with various second-line treatments including osimertinib for patients acquiring the T790M mutation. Methods A total of 737 EGFR mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) patients receiving first-line afatinib treatment were categorized by second-line treatment: T790M+ sequentially treated with osimertinib (cohort A, n=116); T790M− given chemotherapy or others (cohort B, n=143); patients with unknown T790M status (cohort C, n=111); and patients who were undergoing afatinib treatment at the time of data collection, were dead, had discontinued afatinib treatment due to serious adverse events or were lost to follow-up (cohort D, n=367). The primary outcomes were total time on treatment (TOT) and TOT for first-line (TOT-1) and second-line treatments (TOT-2). Secondary outcomes were objective response rates (ORR), overall survival (OS), and central nervous system (CNS) efficacy. Results Median total TOT in cohorts A, B, C, and D were 35.10 months [95% confidence interval (CI): 30.09–43.53 months], 18.80 months (95% CI: 16.92–20.20 months), 12.00 months (95% CI: 10.22–14.98 months), and 42.60 months (95% CI: 30.95–59.23 months), respectively. The ORR of patients given afatinib was 75.7%. In patients with initial brain metastasis without local treatment, the CNS response rate was 67.0% and CNS progression-free survival was 24.70 months (95% CI: 19.84–33.15 months). Conclusions This study showed that sequential approach of afatinib followed by second line treatment is an effective therapeutic strategy for EGFR M+ NSCLC patients.

A Real-World Cohort Study of First-Line Afatinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer in Vietnam

“…1c). However, the mTTF in patients with brain metastases at baseline is consistent with those in studies from Korea (14.8 months) [10] and China (15.6 months) [16]. These ndings support the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases.…”

“…1a). Compared to real-world data worldwide of mTTF ranging from 13.1-18.7 months [10][11][12][13][14][15], the Vietnamese population showed similar effectiveness of rst-line afatinib. In the common mutation group, the mTTF extended to 17.5 months, while in the uncommon mutation group, it was notably shorter at 13.8 months (p = 0.045).…”

Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non–Small-Cell Lung Cancer: Results From LASER301

“…Efficient penetration of the blood-brain barrier (BBB) is critical, as approximately 39% of patients with newly diagnosed advanced EGFR m NSCLC have brain metastases at diagnosis, and nearly 50% of patients develop brain metastases within 5 years of diagnosis despite treatment with early-generation EGFR TKIs. 11,12 Osimertinib has shown improved efficacy in treating brain metastases compared with first/second-generation TKIs (mPFS not reached v 13.9 months, respectively). 13 Osimertinib is the preferred first-line therapy and the only globally approved third-generation TKI for EGFR m locally advanced or metastatic NSCLC; thus, additional treatment options with differentiated properties are needed.…”

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion

“…Selecting an appropriate anticancer drug for patients with NSCLC with frequent EGFR mutations targeted by second- and third-generation agents presents considerable challenges. Although third-generation agents have been reported to exhibit higher or comparable treatment response rates compared to first- and second-generation agents, second-generation agents have also shown substantial efficacy 12 , 13 . In this study, we aimed to identify patients who are sensitive to EGFR anticancer agents using LCOs.…”