NICE has approved dacomitinib monotherapy as a first-line option for untreated locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).
The main clinical evidence for dacomitinib came from the multicentre, open-label, phase 3 randomised controlled ARCHER 1050 trial, which compared the efficacy and safety of dacomitinib (n=227) with gefitinib (n=225) in adults with untreated locally advanced or metastatic EGFR mutation-positive NSCLC. Patients had either the exon 19 deletion (del19) or exon 21 (L858R) EGFR mutation. The trial included 71 study sites in seven countries (China, Hong Kong, Japan, Republic of Korea, Italy, Poland, and Spain).
ARCHER 1050 showed that dacomitinib significantly improved progression-free survival (PFS) compared with gefitinib (14.7 months vs 9.2 months; hazard ratio [HR] 0.589; 95% CI 0.47-0.74). Overall survival was also improved (34.1 months vs 26.8 months; HR 0.760; 95% CI 0.58-0.99). Dacomitinib had a higher incidence of common adverse events (AEs) and required more dose reductions (66.1% and 8.0%, respectively).
To compare dacomitinib with afatinib, NICE conducted a fixed-effects network meta-analysis using data from ARCHER 1050 for dacomitinib and from LUX-Lung 7 for afatinib. The results suggested dacomitinib might be better than afatinib in terms of extending PFS and OS, but there was no significant difference between the two treatments (PFS HR 0.80; 95% CI 0.57-1.12; OS HR 0.88; 95% CI 0.61-1.29).
While there was some uncertainty about cost-effectiveness modelling, NICE concluded that the most plausible cost-effectiveness estimate is within what NICE normally considers an acceptable use of NHS resources.
Dacomitinib is administered as a once-a-day oral dose of 45 mg continued until disease progression or unacceptable toxicity.