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Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment ≥10 months before data entry. Primary outcome was time on treatment; OS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov).

Mutations in the EGFR  gene are particularly prevalent among Chinese patients with non-small-cell lung carcinoma. Six EGFR tyrosine kinase inhibitors are approved for the first-line treatment of EGFR mutation-positive non-small-cell lung carcinoma in China, which poses questions about which agent is most suitable for a particular patient. In this article, we review available clinical trial and real-world data with afatinib in Chinese patients. We assess its efficacy and safety in key patient subgroups such as those with uncommon mutations or brain metastases. We also consider possible subsequent therapies following afatinib. Encouragingly, available data suggest that sequential afatinib and osimertinib confer prolonged overall time to failure of almost 4 years in Asian patients, and represents a viable option in this setting.

Background: We aimed to assess the effectiveness and cost of patients with first line tyrosine kinase inhibitors (TKIs) sequence of first (1G) and second generation (2G) followed by osimertinib. Materials & methods: Using the French nationwide claims and hospitalization database, we analyzed non-small-cell lung cancer patients who had been treated with osimertinib between April 2015 and December 2017, after a first line treatment with a TKI-1G/2G. Results: The median time on treatment for sequential TKI-1G/2G followed by osimertinib was 34 months (95% CI: 31-46); 13 and 12months, respectively for TKI 1G or 2G and TKI 3G, respectively. The median overall survival for sequential TKI 1G or 2G followed by osimertinib was 37 months (95% CI: 34-42). The mean monthly costs per patient was €5162. Conclusion: These results, in line with those observed during clinical trials, confirm the effectiveness of the sequence TKI-1G/2G followed by osimertinib in EGFR -mutated non-small-cell lung cancer.

Aim: Acquired resistance to EGFR tyrosine kinase inhibitors is inevitable in non-small-cell lung cancer. To inform subsequent treatment decisions, we retrospectively assessed therapies following afatinib in Japanese patients from LUX-Lung 3. Patients & methods: LUX-Lung 3 was a randomized, open-label, Phase III study of afatinib versus cisplatin/pemetrexed in treatment-naive patients with EGFR mutation-positive ( EGFR m + ) advanced lung adenocarcinoma. Results: Among 47 Japanese patients who discontinued first-line afatinib, 91/81/62% received ≥one/two/three subsequent therapies. The most common second-line therapies were platinum-based chemotherapy (38%) and a first-generation EGFR tyrosine kinase inhibitor (17%). Median overall survival (afatinib vs cisplatin/pemetrexed) was 47.8 versus 35.0 months (not significant). Conclusion: First-line afatinib does not appear to diminish suitability for subsequent therapies in EGFR m + non-small-cell lung cancer.