A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with many oncogenic driver mutations, including de novo mutations in the Mesenchymal Epithelial Transition (MET) gene (specifically in Exon 14 [ex14]), that lead to tumourigenesis. Acquired alterations in the MET gene, specifically MET amplification is also associated with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutant NSCLC. Although MET has become an actionable biomarker with the availability of MET-specific inhibitors in selected countries, there is differential accessibility to diagnostic platforms and targeted therapies across countries in Asia-Pacific (APAC). The Asian Thoracic Oncology Research Group (ATORG), an interdisciplinary group of experts from Australia, Hong Kong, Japan, Korea, Mainland China, Malaysia, the Philippines, Singapore, Taiwan, Thailand and Vietnam, discussed testing for MET alterations and considerations for using MET-specific inhibitors at a consensus meeting in January 2022, and in subsequent offline consultation. Consensus recommendations are provided by the ATORG group to address the unmet need for standardised approaches to diagnosing MET alterations in NSCLC and for using these therapies. MET inhibitors may be considered for first-line or second or subsequent lines of treatment for patients with advanced and metastatic NSCLC harbouring MET ex14 skipping mutations; MET ex14 testing is preferred within multi-gene panels for detecting targetable driver mutations in NSCLC. For patients with EGFR-mutant NSCLC and MET amplification leading to EGFR TKI resistance, enrolment in combination trials of EGFR TKIs and MET inhibitors is encouraged.