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Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset
S S Ramalingam1, K O'Byrne2, M Boyer3
1Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, USA suresh.ramalingam@emory.edu.
Background:
The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases.
Methods:
The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib.
Results:
One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0-18.2] with dacomitinib and 9.6 months (95% CI 7.4-12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458-1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6-41.5) with dacomitinib versus 23.2 months (95% CI 16.0-31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431-1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib.
Conclusions:
Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721).
Clinical Trials Number:
ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).
Insights
Dacomitinib showed comparable efficacy to erlotinib in non-small cell lung cancer (NSCLC) patients with EGFR mutations. While not statistically significant, dacomitinib demonstrated a trend towards improved progression-free survival and overall survival.
Area of Science:
- Oncology
- Pharmacology
Background:
- Irreversible epidermal growth factor receptor (EGFR) inhibitors show efficacy in NSCLC with activating EGFR mutations.
- Dacomitinib is an irreversible HER family tyrosine kinase inhibitor.
- Comparison of irreversible versus reversible EGFR inhibitors in NSCLC is not well-established.
Purpose of the Study:
- To compare the efficacy of dacomitinib versus erlotinib in patients with locally advanced/metastatic NSCLC and EGFR mutations.
- To evaluate progression-free survival (PFS) and overall survival (OS) in pooled patient data.
Main Methods:
- Pooled data from two randomized studies (ARCHER 1009 and A7471028) comparing dacomitinib to erlotinib.
- Patients had received one or two prior chemotherapy regimens.
- EGFR mutation testing (exon 19 deletion and L858R) was performed centrally on archived tumor samples.
Main Results:
- 101 patients with exon 19/21 EGFR mutations were analyzed.
- Median PFS was 14.6 months for dacomitinib vs. 9.6 months for erlotinib (HR 0.717, P=0.146).
- Median OS was 26.6 months for dacomitinib vs. 23.2 months for erlotinib (HR 0.737, P=0.265).
- Dacomitinib was associated with increased diarrhea and mucositis.
Conclusions:
- Dacomitinib demonstrates comparable efficacy to erlotinib in EGFR-mutated NSCLC patients.
- Patients with exon 19 deletion showed favorable outcomes with dacomitinib.
- A Phase III study (ARCHER 1050) is ongoing to compare dacomitinib with gefitinib in first-line therapy.
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