Dacomitinib triumphs over gefitinib as first-line treatment for advanced EGFR-positive NSCLC
The second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) dacomitinib improved progression-free survival (PFS) by an additional 5 months compared with gefitinib in patients with EGFR-positive non-small cell lung cancer (NSCLC), according to results of the open-label, phase III ARCHER 1050* trial.
“Dacomitinib should be considered as a new treatment option for first-line management of patients with advanced EGFR-mutated NSCLC,” said study investigator Professor Tony Mok from the Chinese University of Hong Kong who presented the findings of the study at the annual meeting of the American Society of Clinical Oncology (ASCO 2017) held in Chicago, Illinois, US.
Four hundred and fifty two patients with advanced (stage IIIB to IV) NSCLC with EGFR-activating mutations, ECOG status 0–1 and no CNS metastasis who had not undergone prior systemic or TKI treatment were randomized to dacomitinib (45 mg QD, n=227, median age 62 years, 64.3 percent female, 74.9 percent Asian) or gefitinib (250 mg QD, n=225, median age 61 years, 55.6 percent female, 78.2 percent Asian).
Median PFS was higher with dacomitinib compared with gefitinib (14.7 vs 9.2 months, hazard ratio, 0.59, 95 percent confidence interval, 0.47–0.74; p<0.0001). [ASCO 2017, abstract LBA9007]
Duration of response also favoured the dacomitinib arm (median 14.8 vs 8.3 months; p<0.0001), while objective response rate was comparable between the dacomitinib and gefitinib arms (74.9 and 71.6 percent of patients, respectively; p=0.3883).
The most common grade 3 adverse events among patients on dacomitinib were dermatitis acneiform (13.7 percent), diarrhoea (8.4 percent), and paronychia (7.5 percent), while the most common grade 3 adverse event among patients on gefitinib was elevation of ALT levels (8.5 percent). There was one incident of grade 5 diarrhoea in patients on dacomitinib.
More patients on dacomitinib needed dose modification compared with gefitinib (66.1 percent vs 8.0 percent).
“We changed the treatment paradigm for EGFR-positive lung cancer a few years ago when targeted therapy replaced chemotherapy,” said Mok. “This study shows that dacomitinib may be an even more effective treatment for these patients. However, patients should be aware of the need to deal with potential side effects when making treatment decisions,” he said.
“Dacomitinib is superior to gefitinib in the front-line setting for EGFR L858R and del 19 mutation-positive NSCLC and represents a new additional standard of care, an alternative to afatinib,” said discussant Dr Sanjay Popat from The Royal Marsden Hospital in London, UK.
“However, toxicities are markedly different to gefitinib and this must be borne in mind in individual patient selection decisions,” said Popat, who highlighted that the use of dacomitinib may be limited by the results of the FLAURA** trial.