Afatinib versus gemcitabine/cisplatin for first-line treatment of Chinese patients with advanced non-small-cell lung cancer harboring <em>EGFR </em>mutations: subgroup analysis of the LUX-Lung 6 trial
Abstract:IntroductionNon-small-cell lung cancer (NSCLC) is the leading cause of cancer death in China. Four epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors – afatinib, erlotinib, icotinib, and gefitinib – are available for first-line treatment of NSCLC in China; however, there are few data to guide treatment choice. The Phase III LUX-Lung 6 trial compared afatinib with platinum-based chemotherapy for first-line treatment of patients from Southeast Asia with EGFR mutation-positive advanced NS… Show more
“…50 Similar findings were reported in a sub-analysis of 83 Japanese patients from LUX-Lung 353 and in a sub-analysis of 327 patients from mainland China enrolled in the LUX-Lung 6 study (Table 1). 54 In LUX-Lung 7, there was no significant difference in OS between afatinib and gefitinib in patients with del19 mutations (Table 1; Figure 3C). Figure 3Subgroup analyses of overall survival in ( A ) in LUX-Lung 3 (del19 and L858R mutations only).…”
Section: Clinical Efficacy In Egfr Mutation-positive Advanced Nsclc Pmentioning
confidence: 92%
“…In 24 patients with G719X, S768I, or L861Q mutations, median PFS was 18.3 months with afatinib and 2.6 months for both erlotinib and gefitinib. Subsequent to these reports, and on the basis of the results from the LUX-Lung 2, 3, and 6 trials, the United States FDA approval for afatinib was extended to include patients with these mutations 54…”
Section: First-line Clinical Efficacy In Patient Subgroupsmentioning
The discovery that mutations in the
EGFR
gene are present in up to 50% of patients with lung adenocarcinoma, and the development of highly efficacious EGFR tyrosine kinase inhibitors (TKIs), has revolutionized the way this common malignancy is treated. Three generations of EGFR TKIs are now approved for use in
EGFR
mutation-positive non-small cell lung cancer (NSCLC); the first-generation agents erlotinib, gefitinib, and icotinib; the second-generation ErbB family blockers afatinib and dacomitinib; and most recently, osimertinib, a third-generation EGFR TKI. The second-generation agents have demonstrated impressive efficacy relative to both standard platinum-based chemotherapy and first-generation EGFR TKIs, significantly improving response and progression-free and overall survival. Data from real-world studies suggest that afatinib is as effective and well tolerated in routine clinical practice as it is in clinical studies and is effective in patients with certain uncommon
EGFR
mutations, patients with brain metastases, and older patients. Few real-world data are available for dacomitinib in the first-line setting. Afatinib and dacomitinib have similar safety profiles, with acne/skin dryzness, diarrhea, stomatitis, and paronychia the most common adverse events (AEs) reported in clinical and real-world studies. Numerous studies have shown that tolerability-guided dose reductions can help manage afatinib-related AEs without reducing efficacy. As the number of therapeutic options for advanced NSCLC increases, the optimal choice for first-line treatment will be determined by considering patient factors such as the presence of brain metastases, the type of
EGFR
mutation, tolerability, and subsequent therapy options for long-term treatment.
“…50 Similar findings were reported in a sub-analysis of 83 Japanese patients from LUX-Lung 353 and in a sub-analysis of 327 patients from mainland China enrolled in the LUX-Lung 6 study (Table 1). 54 In LUX-Lung 7, there was no significant difference in OS between afatinib and gefitinib in patients with del19 mutations (Table 1; Figure 3C). Figure 3Subgroup analyses of overall survival in ( A ) in LUX-Lung 3 (del19 and L858R mutations only).…”
Section: Clinical Efficacy In Egfr Mutation-positive Advanced Nsclc Pmentioning
confidence: 92%
“…In 24 patients with G719X, S768I, or L861Q mutations, median PFS was 18.3 months with afatinib and 2.6 months for both erlotinib and gefitinib. Subsequent to these reports, and on the basis of the results from the LUX-Lung 2, 3, and 6 trials, the United States FDA approval for afatinib was extended to include patients with these mutations 54…”
Section: First-line Clinical Efficacy In Patient Subgroupsmentioning
The discovery that mutations in the
EGFR
gene are present in up to 50% of patients with lung adenocarcinoma, and the development of highly efficacious EGFR tyrosine kinase inhibitors (TKIs), has revolutionized the way this common malignancy is treated. Three generations of EGFR TKIs are now approved for use in
EGFR
mutation-positive non-small cell lung cancer (NSCLC); the first-generation agents erlotinib, gefitinib, and icotinib; the second-generation ErbB family blockers afatinib and dacomitinib; and most recently, osimertinib, a third-generation EGFR TKI. The second-generation agents have demonstrated impressive efficacy relative to both standard platinum-based chemotherapy and first-generation EGFR TKIs, significantly improving response and progression-free and overall survival. Data from real-world studies suggest that afatinib is as effective and well tolerated in routine clinical practice as it is in clinical studies and is effective in patients with certain uncommon
EGFR
mutations, patients with brain metastases, and older patients. Few real-world data are available for dacomitinib in the first-line setting. Afatinib and dacomitinib have similar safety profiles, with acne/skin dryzness, diarrhea, stomatitis, and paronychia the most common adverse events (AEs) reported in clinical and real-world studies. Numerous studies have shown that tolerability-guided dose reductions can help manage afatinib-related AEs without reducing efficacy. As the number of therapeutic options for advanced NSCLC increases, the optimal choice for first-line treatment will be determined by considering patient factors such as the presence of brain metastases, the type of
EGFR
mutation, tolerability, and subsequent therapy options for long-term treatment.
“…Other studies indicate that afatinib is effective in specific Asian populations. In a Chinese subanalysis of LUX-Lung 6, median PFS with afatinib was 11.0 months and median OS was 23.6 months (Table 1) [45]. PFS benefit over chemo was significant both in patients with Del19 (HR: 0.21) and L858R mutations (HR: 0.33).…”
Section: Second-generation Egfr Tkis (Erbb Family Blockers) In Asian and Non-asian Populationsmentioning
Few data are available that have compared outcomes with different EGFR tyrosine kinase inhibitors (TKIs) specifically in Asian patients with EGFR mutation-positive non-small-cell lung cancer. In this narrative review, we have collated available data from prospective studies that have assessed first-, second- and third-generation EGFR TKIs in Asian populations, including subanalyses in individual countries (China and Japan). These data indicate that outcomes with first- and second-generation TKIs are broadly similar in Asian and non-Asian populations. However, while the third-generation EGFR TKI, osimertinib, confers significant overall survival benefit over erlotinib/gefitinib in non-Asians, this is not apparent in Asians, particularly in countries like Japan with well-resourced healthcare. Head-to-head comparisons of second- and third-generation EGFR TKIs, with OS as a primary end point, should be considered in Asia.
“…Although no LUX-Lung 3 trial sites were located in mainland China, 72% of patients were East Asian, drawn from sites in Taiwan, Hong Kong, Thailand, South Korea and Japan [22]. LUX-Lung 6 was conducted in China, Thailand and South Korea, with almost 90% of afatinib-treated patients from China [23,31].…”
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.
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