Gefitinib vs Afatinib
Overview
Gefitinib (1st-gen) and afatinib (2nd-gen) are both options for EGFR-mutated NSCLC when osimertinib is unavailable. LUX-Lung 7 showed afatinib superior PFS vs. gefitinib, though OS was similar due to post-progression crossover.
Mechanism of Action
Gefitinib: reversible ATP-competitive EGFR inhibitor. Afatinib: irreversible pan-ErbB inhibitor.
Clinical Evidence
LUX-Lung 7 (head-to-head): afatinib 40 mg vs gefitinib 250 mg in EGFR-mutated NSCLC. Afatinib demonstrated superior PFS (11.0 vs 10.9 months, HR 0.73), time-to-treatment failure, and objective response rate. OS was not significantly different, likely due to post-progression treatment.
Tolerability
Afatinib more toxic (diarrhea, rash, mucositis) but dose reductions to 30 mg improve tolerability without significant loss of efficacy (Post-hoc analysis). Gefitinib better tolerated with fewer Grade 3 adverse events.
Key Takeaways
- Afatinib: superior PFS in LUX-Lung 7; more toxic
- Gefitinib: better tolerated; equivalent OS in LUX-Lung 7
- Both 2nd-choice behind osimertinib for EGFR-mutated NSCLC
Verdict
Afatinib is preferred over gefitinib when PFS improvement and maximum efficacy are prioritized (LUX-Lung 7 data). Gefitinib may be preferred in elderly patients or those with poor performance status where tolerability is paramount. Both are second-line options behind osimertinib.