Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer and EGFR-Activating Mutations

Abstract

Purpose ARCHER 1050, a randomized, open-label, phase III study of dacomitinib versus gefitinib in treatment-naïve patients with advanced non-small-cell lung cancer (NSCLC) and activating mutations in EGFR, reported significant improvement in progression-free survival with dacomitinib. The mature overall survival (OS) analysis for the intention-to-treat population is presented here. Patients and Methods In this multinational, multicenter study, patients age 18 years or older (≥ 20 years in Japan and Korea) who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and newly diagnosed NSCLC with activating mutations in EGFR (exon 19 deletion or exon 21 L858R) were enrolled and randomly assigned in a 1:1 manner to dacomitinib (n = 227) or gefitinib (n = 225). Random assignment was stratified by race (Japanese, Chinese, other East Asian, or non-Asian) and EGFR mutation type. The final OS analysis was conducted with a data cutoff date of February 17, 2017; at that time 220 deaths (48.7%) were observed. Results During a median follow-up time of 31.3 months, 103 (45.4%) and 117 (52.0%) deaths occurred in the dacomitinib and gefitinib arms, respectively. The estimated hazard ratio for OS was 0.760 (95% CI, 0.582 to 0.993; two-sided P = .044). The median OS was 34.1 months with dacomitinib versus 26.8 months with gefitinib. The OS probabilities at 30 months were 56.2% and 46.3% with dacomitinib and gefitinib, respectively. Preliminary subgroup analyses for OS that are based on baseline characteristics were consistent with the primary OS analysis. Conclusion In patients with advanced NSCLC and EGFR activating mutations, dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor (TKI) to show significant improvement in OS in a phase III randomized study compared with a standard-of-care TKI. Dacomitinib should be considered one of the standard treatment options for these patients.

Real‐world health utility scores and toxicities to tyrosine kinase inhibitors in epidermal growth factor receptor mutated advanced non‐small cell lung cancer

“…Mutations in the epidermal growth factor receptor gene (EGFR) are the most common and actionable molecular aberrations in non-small cell lung cancer (NSCLC). [1][2][3] Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in the treatment of advanced lung cancers harbouring EGFR mutations (EGFRm), [4][5][6][7] but remain expensive especially given continuous dosing for the duration that a patient benefits from these TKIs. 8,9 Efficacy of these EGFR-TKIs is not in question.…”

“…First generation (gefitinib, erlotinib) and second generation (afatinib, dacomitinib) EGFR-TKIs have demonstrated improved progression-free survival (PFS), objective response rates, and tolerability when compared to first-line platinum doublet chemotherapy. [4][5][6][7] However, acquired resistance to EGFR-TKIs develops over time. The most common mechanism of resistance leading to failure of first-and second-generation TKIs is a secondary mutation in the EGFR gene, Thr790Met (T790M), found in up to 60% of patients.…”

AKIP1 expression in tumor tissue as a new biomarker for disease monitoring and prognosis in non‐small cell lung cancer: Results of a retrospective study

“…Similar to many other carcinomas, NSCLC is united by having multiple genetic abnormalities, such as the epidermal growth factor receptor (EFGR) and c-ros oncogene 1 (ROS1) mutations, and those genetic features also contribute to the improvement pf NSCLC management. [13][14][15][16] Besides these altered genes, a diverse class of protein biomarkers also exist in the development of individualized treatment of NSCLC, and there have been studies indicate that combining biomarkers may have more satisfactory effect in the diagnosis and prognosis in NSCLC patients compared with a single genetic or protein biomarker. 17 Hence, researching for more biomarkers which could reinforce the detection rate and prognosis of patients with NSCLC is of urgent need.…”

Is there a role for dacomitinib, a second-generation irreversible inhibitor of the epidermal-growth factor receptor tyrosine kinase, in advanced non-small cell lung cancer?

“…The 22 (9.7%) patients treated with osimertinib as second-line agent after dacomitinib showed a median OS of 36.7 months (30.1 to NR), result that was better compared to the median OS reached with chemotherapy as second-line option. However, this result should be interpreted with caution since the number of patients in this group was small [27]. Another retrospective study on the efficacy of second-line osimertinib is the GioTag study [55], a global observational study, assessing as first end-point the time on treatment.…”

“…Recently, Mok et al [27] presented the mature results from OS analysis of ARCHER 1050 patient population, after a 30-month follow-up: OS in the dacomitinib group was significantly improved compared to gefitinib (HR 0.760, 95% CI 0.582-0.993, two-sided P = 0.0438), with median OS of 34.1 months with dacomitinib and 26.8 months with gefitinib. It should be noted that this study demonstrated for the first time an improvement in OS, comparing a second-generation EGFR-TKI to a standard of care EGFR-TKI.…”