Drug updated on 4/24/2024
| Dosage Form | Tablet (oral; 20 mg, 30 mg, 40 mg) |
| Drug Class | Kinase inhibitors |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test.
- Indicated for the treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy.
Summary
- Afatinib demonstrated superior response rates in patients with specific uncommon EGFR mutations such as G719X, S768I, E709X, and L747X compared to first or third-generation TKIs. It was particularly effective in compound mutations involving G719X, E709X, or S768I.
- Fourteen systematic reviews/meta-analyses provided information on the effectiveness and safety of Afatinib in treating various forms of non-small cell lung cancer (NSCLC), including those with different EGFR mutations.
- Compared to osimertinib, afatinib showed a superior progression-free survival benefit despite a slightly lower objective response rate in patients with NSCLC harboring uncommon EGFR mutations. The safety and efficacy were comparable between both drugs for patients with or without brain metastases.
- No significant overall survival benefit was observed from using afatinib over conventional chemotherapies among Asian populations who have an L858R mutation or exon 19 deletion.
- In terms of toxicity profile and dosing strategies, afatinib, along with dacomitinib, had greater toxicity compared to other EGFR-TKIs such as osimertinib, which has a more favorable safety profile. High-dose intermittent strategies reported manageable toxicity levels while increasing maximum plasma concentrations.
- There is no significant difference between the effectiveness of a 30 mg dose versus a 40 mg dose in treating NSCLC patients using afatinib, but the former dosage level is associated with significantly less severe adverse events like diarrhea and rash.
- Afatinib monotherapy improved survival rates among NSCLC patient groups, especially if administered as a first-line treatment option, whereas second-line monotherapy showed promise in squamous NSCLC progressing after platinum-based chemotherapy.
- Afatinib had a significantly lower T790M mutation acquisition rate compared to first-generation TKIs (gefitinib, erlotinib), suggesting a potential advantage in delaying resistance mechanisms.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Gilotrif (afatinib) Prescribing Information. | 2022 | Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Non-small cell lung cancer treatment (PDQ®)–Health professional version. | 2024 | National Cancer Institute |
| Oncogene-addicted metastatic non-small-cell lung cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. | 2023 | Annals of Oncology |
| Non–small cell lung cancer, version 3.2022. | 2022 | Journal of National Comprehensive Cancer Network |
| Japanese lung cancer society guidelines for stage IV NSCLC with EGFR mutations. | 2021 | JTO Clinical and Research Reports |
| Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. | 2020 | European Society for Medical Oncology |