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Showed that the second-generation EGFR pill afatinib beats chemotherapy for lung cancers driven by an EGFR mutation, and that the benefit is largest for the two common mutations.
LUX-Lung 3 screened 1,269 patients and randomised 345 with EGFR-mutant stage IIIB or IV lung adenocarcinoma 2:1 to afatinib 40 mg daily or to cisplatin with pemetrexed for up to six cycles, stratified by mutation type (exon 19 deletion, L858R, or other) and race.
Median progression-free survival by independent review was 11.1 months with afatinib against 6.9 months with chemotherapy (hazard ratio 0.58, 95 percent confidence interval 0.43 to 0.78, p=0.001). Among the 308 patients with an exon 19 deletion or L858R, it was 13.6 against 6.9 months (hazard ratio 0.47, 0.34 to 0.65, p=0.001). Diarrhoea, rash or acne and stomatitis were the characteristic afatinib toxicities; patient-reported cough, breathlessness and pain were better controlled with afatinib.
Afatinib is a covalent pan-ErbB inhibitor, and the later pooled analysis of LUX-Lung 2, 3 and 6 is the main evidence for treating the uncommon EGFR mutations G719X, L861Q and S768I, for which it holds a distinct FDA indication, granted in 2018, that osimertinib does not.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
345 randomised.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (independent review)primary | Afatinib | - | 11.1 months | 0.58 (0.43 to 0.78) | 0.001 | link |
| Cisplatin and pemetrexed | - | 6.9 months | ||||
| Progression-free survival, exon 19 deletion or L858R | Afatinib | - | 13.6 months | 0.47 (0.34 to 0.65) | 0.001 | link |
| Cisplatin and pemetrexed | - | 6.9 months |
Shares FLAURA, Tyrosine kinase inhibitor (TKI), Pemetrexed, EGFR-mutated non-small-cell lung cancer.
Shares Pemetrexed, EGFR-mutated non-small-cell lung cancer, Cisplatin, Platinum agents.
Shares Pemetrexed, EGFR-mutated non-small-cell lung cancer, Cisplatin, Platinum agents.
Shares Pemetrexed, EGFR-mutated non-small-cell lung cancer, Cisplatin, Platinum agents.
Shares Pemetrexed, EGFR-mutated non-small-cell lung cancer, Cisplatin, Platinum agents.
Shares Pemetrexed, EGFR-mutated non-small-cell lung cancer, Cisplatin, Platinum agents.
Shares Pemetrexed, EGFR-mutated non-small-cell lung cancer, Platinum agents, Small-molecule kinase inhibitors.
Shares Pemetrexed, EGFR-mutated non-small-cell lung cancer, Cisplatin, Platinum agents.