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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Afatinib: A Review in Advanced Non-Small Cell Lung Cancer
1Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand. demail@springer.com.
Abstract:
Afatinib (Giotrif®, Gilotrif®) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. In the first-line treatment of patients with advanced lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations, afatinib significantly prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS), compared with gefitinib (LUX-Lung 7 trial). In the overall population of patients receiving first-line treatment for advanced lung adenocarcinoma with activating EGFR mutations, afatinib significantly prolonged PFS, but not OS, compared with pemetrexed plus cisplatin (LUX-Lung 3 trial) or gemcitabine plus cisplatin (LUX-Lung 6 trial). However, in both LUX-Lung 3 and LUX-Lung 6, OS was significantly prolonged in the subgroup of patients with deletions in exon 19 receiving afatinib versus chemotherapy. In the second-line treatment of advanced squamous non-small cell lung cancer (NSCLC), afatinib significantly prolonged PFS and OS, compared with erlotinib, regardless of EGFR mutation status (LUX-Lung 8 trial). Afatinib had a predictable and manageable tolerability profile in patients with advanced NSCLC. In conclusion, afatinib is an important option for the first-line treatment of patients with advanced NSCLC and activating EGFR mutations, and provides an additional option for the treatment of patients with squamous NSCLC that has progressed following first-line platinum-based chemotherapy.
Insights
Afatinib improves progression-free survival in advanced lung cancer patients with EGFR mutations. It also shows benefits in second-line squamous non-small cell lung cancer, offering a valuable treatment option.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Afatinib is an irreversible ErbB family tyrosine kinase inhibitor.
- Epidermal growth factor receptor (EGFR) mutations are key drivers in lung adenocarcinoma.
- Non-small cell lung cancer (NSCLC) remains a significant global health challenge.
Purpose of the Study:
- To evaluate afatinib's efficacy and safety in advanced NSCLC.
- To compare afatinib with gefitinib, chemotherapy, and erlotinib in different NSCLC settings.
- To assess afatinib's impact on progression-free survival (PFS), overall survival (OS), and time to treatment failure (TTF).
Main Methods:
- Analysis of data from LUX-Lung 3, 6, 7, and 8 clinical trials.
- Comparison of afatinib versus gefitinib in first-line advanced EGFR-mutated lung adenocarcinoma.
- Evaluation of afatinib versus chemotherapy (pemetrexed/cisplatin or gemcitabine/cisplatin) in first-line advanced EGFR-mutated lung adenocarcinoma.
- Assessment of afatinib versus erlotinib in second-line advanced squamous NSCLC.
Main Results:
- Afatinib significantly prolonged PFS and TTF versus gefitinib in first-line EGFR-mutated lung adenocarcinoma (LUX-Lung 7).
- Afatinib significantly prolonged PFS versus chemotherapy in first-line EGFR-mutated lung adenocarcinoma (LUX-Lung 3 & 6), with improved OS in exon 19 deletion subgroup.
- Afatinib significantly prolonged PFS and OS versus erlotinib in second-line squamous NSCLC (LUX-Lung 8).
Conclusions:
- Afatinib is a crucial option for first-line treatment of advanced NSCLC with activating EGFR mutations.
- Afatinib offers an additional treatment choice for advanced squamous NSCLC progressing after chemotherapy.
- Afatinib demonstrates a manageable tolerability profile in advanced NSCLC patients.
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