Dacomitinib improves EGFR-mutated NSCLC PFS over gefitinib, but at toxicity cost
medwireNews: The ARCHER 1050 investigators believe that their results establish dacomitinib as an addition to the first-line EGFR mutation-positive non-small-cell lung cancer (NSCLC) treatment armamentarium, but caution that the associated toxicity needs to be managed.
Among 227 patients with treatment-naïve, stage IIIB–IV disease who were randomly assigned to receive oral dacomitinib 45 mg once daily in this phase III trial, median progression-free survival (PFS) as evaluated by independent review was 14.7 months after a median follow-up of 22.1 months. This compared with a median PFS of 9.2 months for the 225 participants treated with gefitinib 250 mg/day, a significant difference giving a hazard ratio of 0.59.
Tony Mok, from the Chinese University of Hong Kong, who presented the results at the 2017 annual meeting of the American Society of Clinical Oncology, pointed out that the Kaplan–Meier curves overlapped up to about 6 months, after which dacomitinib-treated patients had better PFS than those given gefitinib.
The corresponding 24-month PFS rates were 30.6% and 9.6%, equating to a substantial difference of 21% in favor of dacomitinib, he told the audience in Chicago, Illinois, USA.
The PFS gain offered by dacomitinib was evident in the majority of subgroups, except when participants were stratified by race. PFS was significantly better with dacomitinib than gefitinib among Asian patients, but this was not the case for non-Asians, which Mok believes could be due to the smaller sample size, given that around 75% of participants in each arm were of Asian ethnicity.
The objective response rate was comparable between the dacomitinib and gefitinib trial arms (74.9 and 71.6%, respectively), but the duration of response was significantly longer with the second-generation EGFR tyrosine kinase inhibitor, at a median of 14.8 months compared with 8.3 months for gefitinib.
This more potent inhibition was associated, however, with higher toxicity, commented Mok. Certain adverse events of grade 3 or worse were more common with dacomitinib than gefitinib, such as dermatitis acneiform (13.7% vs none), diarrhea (8.8% vs 0.9%), paronychia (7.5 vs 1.3%), and stomatitis (3.5 vs 0.4%).
A higher proportion of patients in the dacomitinib than the gefitinib group required a dose reduction, at 66.1% versus 8.0%, but the incidence of treatment-related deaths was low, at two and one, respectively.
The presenter also highlighted that despite the toxicity the global quality of life scores as reported by patients using the EORTC-QLQ-C30 and LC13 questionnaires did not worsen relative to baseline in the dacomitinib arm.
He concluded: “Dacomitinib should be considered as a new treatment option for first-line management of patients with advanced EGFR-mutated NSCLC.
“In addition to the three existing drugs, now we have the fourth one.”
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