Background
Phase III, open-label RCT; N=452; treatment-naive unresectable metastatic NSCLC with EGFR ex19del or L858R; excluded CNS metastases; randomized 1:1.
Interventions and follow up
Arm A: Dacomitinib 45 mg PO daily
Arm B: Gefitinib 250 mg PO daily
Primary endpoint: PFS by blinded independent review
mFollow up: 22.1 mo
Arm B: Gefitinib 250 mg PO daily
Primary endpoint: PFS by blinded independent review
mFollow up: 22.1 mo
Results
mPFS: 14.7 mo vs 9.2 mo; HR 0.59 (95%CI 0.47–0.74); P<.0001
mOS (final update): 34.1 mo vs 26.8 mo; HR 0.76 (95%CI 0.58–0.99); two-sided P=.044
mOS (final update): 34.1 mo vs 26.8 mo; HR 0.76 (95%CI 0.58–0.99); two-sided P=.044
Adverse events
Skin: grade 3-4 dermatitis acneiform 14% vs 0%
GI: grade 3-4 diarrhea 9% vs 1%
Dose modifications: permanent discontinuation 10% vs 7%; temporary interruption 78% vs 54%; dose reduction 66% vs 8%
GI: grade 3-4 diarrhea 9% vs 1%
Dose modifications: permanent discontinuation 10% vs 7%; temporary interruption 78% vs 54%; dose reduction 66% vs 8%
Conclusions
Dacomitinib improved PFS and OS vs gefitinib first-line in EGFR ex19del/L858R advanced NSCLC, but use is limited by high toxicity and frequent dose reductions.
Key Limitations
High rate of dose reductions/interruptions; excluded CNS metastases; comparator was first-generation TKI (not osimertinib); open-label design; significant skin/GI toxicity limits tolerability.
Clinical Context
Dacomitinib FDA approved first-line for EGFR ex19del/L858R NSCLC (2018). ESMO/ASCO prefer osimertinib first-line given CNS activity and tolerability; dacomitinib is a less-used alternative.