Dacomitinib

A multicenter open-label, phase III trial (ARCHER 1050 [NCT01774721]) compared dacomitinib, a second-generation, irreversible EGFR TKI, administered orally at a dose of 45 mg per day with gefitinib administered orally at a dose of 250 mg per day, as first-line therapy in patients with newly diagnosed advanced NSCLC and the following EGFR variants: EGFR exon 19 deletion or EGFR L858R variants, as detected by an FDA-approved test.[53] Four hundred and fifty-two eligible patients were randomly assigned in a 1:1 ratio. The primary end point was PFS assessed by masked independent review in the intention-to-treat (ITT) population.

A multicenter open-label, phase III trial (ARCHER 1050 [NCT01774721]) compared dacomitinib, a second-generation, irreversible EGFR TKI, administered orally at a dose of 45 mg per day with gefitinib administered orally at a dose of 250 mg per day, as first-line therapy in patients with newly diagnosed advanced NSCLC and the following EGFR variants: EGFR exon 19 deletion or EGFR L858R variants, as detected by an FDA-approved test.[53] Four hundred and fifty-two eligible patients were randomly assigned in a 1:1 ratio. The primary end point was PFS assessed by masked independent review in the intention-to-treat (ITT) population.

Median PFS was 14.7 months in the dacomitinib group and 9.2 months in the gefitinib group (HR, 0.59; 95% CI, 0.47−0.74; P < .0001).[53][Level of evidence B1]

A multicenter open-label, phase III trial (ARCHER 1050 [NCT01774721]) compared dacomitinib, a second-generation, irreversible EGFR TKI, administered orally at a dose of 45 mg per day with gefitinib administered orally at a dose of 250 mg per day, as first-line therapy in patients with newly diagnosed advanced NSCLC and the following EGFR variants: EGFR exon 19 deletion or EGFR L858R variants, as detected by an FDA-approved test.[53] Four hundred and fifty-two eligible patients were randomly assigned in a 1:1 ratio. The primary end point was PFS assessed by masked independent review in the intention-to-treat (ITT) population.

The objective response rate was similar between the two groups (75% for the dacomitinib group vs. 72% for the gefitinib group; P = 0.42).

A multicenter open-label, phase III trial (ARCHER 1050 [NCT01774721]) compared dacomitinib, a second-generation, irreversible EGFR TKI, administered orally at a dose of 45 mg per day with gefitinib administered orally at a dose of 250 mg per day, as first-line therapy in patients with newly diagnosed advanced NSCLC and the following EGFR variants: EGFR exon 19 deletion or EGFR L858R variants, as detected by an FDA-approved test.[53] Four hundred and fifty-two eligible patients were randomly assigned in a 1:1 ratio. The primary end point was PFS assessed by masked independent review in the intention-to-treat (ITT) population.

The median DOR was longer in the dacomitinib group (14.8 months vs. 8.3 months; HR, 0.4; 95% CI, 0.31−0.53; P < .0001).

A multicenter open-label, phase III trial (ARCHER 1050 [NCT01774721]) compared dacomitinib, a second-generation, irreversible EGFR TKI, administered orally at a dose of 45 mg per day with gefitinib administered orally at a dose of 250 mg per day, as first-line therapy in patients with newly diagnosed advanced NSCLC and the following EGFR variants: EGFR exon 19 deletion or EGFR L858R variants, as detected by an FDA-approved test.[53] Four hundred and fifty-two eligible patients were randomly assigned in a 1:1 ratio. The primary end point was PFS assessed by masked independent review in the intention-to-treat (ITT) population.

The median OS was 34.1 months with dacomitinib vs. 26.8 months with gefitinib (HR, 0.76; 95% CI, 0.58−0.99; P = .44).[53]

A multicenter open-label, phase III trial (ARCHER 1050 [NCT01774721]) compared dacomitinib, a second-generation, irreversible EGFR TKI, administered orally at a dose of 45 mg per day with gefitinib administered orally at a dose of 250 mg per day, as first-line therapy in patients with newly diagnosed advanced NSCLC and the following EGFR variants: EGFR exon 19 deletion or EGFR L858R variants, as detected by an FDA-approved test.[53] Four hundred and fifty-two eligible patients were randomly assigned in a 1:1 ratio. The primary end point was PFS assessed by masked independent review in the intention-to-treat (ITT) population.

Grade 3 or higher adverse events of any cause occurred in 63% of patients who received dacomitinib and 41% of patients who received gefitinib. The most common grade 3 or 4 adverse events were dermatitis acneiform (14% in the dacomitinib group vs. none in the gefitinib group), diarrhea (8% vs. 1%), and raised alanine aminotransferase (ALT) levels (1% vs. 8%). Serious treatment-related adverse events were more frequent in the dacomitinib group (9% vs. 4%). Permanent discontinuation of the study drug because of treatment-related adverse events occurred more often in the dacomitinib group (10% vs. 7%). Dose reductions were also more frequent in the dacomitinib group (66% vs. 8%).