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ARCHER 1050 showed that dacomitinib, a second-generation EGFR pill, kept untreated EGFR-mutant lung cancer under control longer than gefitinib, and a later analysis reported longer survival, though rash and diarrhoea were harsher and patients with brain metastases were excluded.
ARCHER 1050 was an open-label, randomised phase 3 trial at 71 centres in seven countries or regions that compared dacomitinib with gefitinib in 452 patients with newly diagnosed advanced non-small-cell lung cancer carrying an EGFR exon 19 deletion or L858R mutation. Patients received dacomitinib 45 mg once daily (227) or gefitinib 250 mg once daily (225). Randomisation was stratified by race and EGFR mutation type, patients with brain metastases were excluded, and the primary endpoint was progression-free survival by masked independent review.
Median progression-free survival was 14.7 months with dacomitinib against 9.2 months with gefitinib (hazard ratio 0.59, 95% CI 0.47 to 0.74; The Lancet Oncology 2017). By independent review 74.9 percent of patients responded on dacomitinib against 71.6 percent on gefitinib, a difference that was not statistically significant, and responses lasted a median of 14.8 against 8.3 months (registry results and US label). A separate mature analysis reported median overall survival of 34.1 months against 26.8 months (hazard ratio 0.76, 95% CI 0.58 to 0.99; Journal of Clinical Oncology 2018). The US label notes that overall survival was not formally tested, because the response rate comparison earlier in the prespecified testing order was not significant. Grade 3 or 4 dermatitis acneiform (14 percent) and diarrhoea (8 percent) were more common on dacomitinib.
The trial supported the 2018 US first-line approval of dacomitinib. Mok and colleagues described it as the first second-generation EGFR inhibitor to show an overall survival gain over a standard EGFR inhibitor in a phase 3 trial. FLAURA later made osimertinib the usual first-line EGFR inhibitor and displaced dacomitinib.
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.
452 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (masked independent review)primary | Dacomitinib | 227 | 14.7 months | 0.59 (0.47 to 0.74) | - | link |
| Gefitinib | 225 | 9.2 months | ||||
| Overall survival (mature analysis) | Dacomitinib | 227 | 34.1 months | 0.76 (0.582 to 0.993) | 0.044 | link |
| Gefitinib | 225 | 26.8 months | ||||
| Objective response rate (independent radiologic review) | Dacomitinib | 227 | 74.9% | - | - | link |
| Gefitinib | 225 | 71.6% | ||||
| Duration of response (independent radiologic review) | Dacomitinib | - | 14.8 months | - | - | link |
| Gefitinib | - | 8.3 months |
This is the separate paper behind the survival figure quoted for dacomitinib. It is a real but modest gain, and the US label notes that overall survival was not formally tested because the response rate comparison earlier in the testing order was not significant, so the P value is descriptive.
ARCHER 1050 supported dacomitinib's 2018 US first-line approval and was the first head-to-head win of a second-generation EGFR inhibitor over a first-generation one on progression-free survival. FLAURA, reported the same year, made osimertinib the usual first choice, so dacomitinib is now rarely used.
Shares FLAURA, Tyrosine kinase inhibitor (TKI), Brain metastases (intracranial disease), EGFR-mutated non-small-cell lung cancer.
Shares Dacomitinib, EGFR exon 19 deletion & L858R, Gefitinib, EGFR.
Shares Tony S. K. Mok, Gefitinib, EGFR-mutated non-small-cell lung cancer, EGFR.
Shares Dacomitinib, Pfizer (incl. Seagen), Non-small-cell lung cancer.
Shares LUX-Lung 3, Gefitinib, Tyrosine kinase inhibitor (TKI), EGFR-mutated non-small-cell lung cancer.
Shares FLAURA, EGFR-mutated non-small-cell lung cancer, EGFR, Non-small-cell lung cancer.
Shares Tony S. K. Mok, Tyrosine kinase inhibitor (TKI), Brain metastases (intracranial disease), Lung cancer (all types).
Shares Dacomitinib, EGFR-mutated non-small-cell lung cancer, Non-small-cell lung cancer.