Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial - 28/10/14
, Pasi A Jänne, ProfMD b, Tony Mok, ProfMD c, Kenneth O’Byrne, ProfMD d, Michael J Boyer, ProfMD e, Joachim Von Pawel, ProfMD f, Adam Pluzanski, MD g, Mikhail Shtivelband, MD h, Lara Iglesias Docampo, MD i, Jaafar Bennouna, MD j, Hui Zhang, PhD k, Jane Q Liang, PhD l, Jim P Doherty, PhD m, Ian Taylor, PhD l, Cecile B Mather, MS l, Zelanna Goldberg, MD n, Joseph O’Connell, MD m, Luis Paz-Ares, ProfMD oSummary |
Background |
Dacomitinib is an irreversible pan-EGFR family tyrosine kinase inhibitor. Findings from a phase 2 study in non-small cell lung cancer showed favourable efficacy for dacomitinib compared with erlotinib. We aimed to compare dacomitinib with erlotinib in a phase 3 study.
Methods |
In a randomised, multicentre, double-blind phase 3 trial in 134 centres in 23 countries, we enrolled patients who had locally advanced or metastatic non-small-cell lung cancer, progression after one or two previous regimens of chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, and presence of measurable disease. We randomly assigned patients in a 1:1 ratio to dacomitinib (45 mg/day) or erlotinib (150 mg/day) with matching placebo. Treatment allocation was masked to the investigator, patient, and study funder. Randomisation was stratified by histology (adenocarcinoma vs non-adenocarcinoma), ethnic origin (Asian vs non-Asian and Indian sub-continent), performance status (0–1 vs 2), and smoking status (never-smoker vs ever-smoker). The coprimary endpoints were progression-free survival per independent review for all randomly assigned patients, and for all randomly assigned patients with KRAS wild-type tumours. The study has completed accrual and is registered with ClinicalTrials.gov, number NCT01360554.
Findings |
Between June 22, 2011, and March 12, 2013, we enrolled 878 patients and randomly assigned 439 to dacomitinib (256 KRAS wild type) and 439 (263 KRAS wild type) to erlotinib. Median progression-free survival was 2·6 months (95% CI 1·9–2·8) in both the dacomitinib group and the erlotinib group (stratified hazard ratio [HR] 0·941, 95% CI 0·802–1·104, one-sided log-rank p=0·229). For patients with wild-type KRAS, median progression-free survival was 2·6 months for dacomitinib (95% CI 1·9–2·9) and erlotinib (95% CI 1·9–3·0; stratified HR 1·022, 95% CI 0·834–1·253, one-sided p=0·587). In patients who received at least one dose of study drug, the most frequent grade 3–4 adverse events were diarrhoea (47 [11%] patients in the dacomitinib group vs ten [2%] patients in the erlotinib group), rash (29 [7%] vs 12 [3%]), and stomatitis (15 [3%] vs two [<1%]). Serious adverse events were reported in 52 (12%) patients receiving dacomitinib and 40 (9%) patients receiving erlotinib.
Interpretation |
Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non-small-cell lung cancer or in patients with KRAS wild-type tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations.
Funding |
Pfizer.
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Vol 15 - N° 12
P. 1369-1378 - novembre 2014 Retour au numéro
Article précédent
- Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT3VIN): a multicentre, open-label, randomised, phase 2 trial
- Amanda Tristram, Christopher N Hurt, Tracie Madden, Ned Powell, Stephen Man, Sam Hibbitts, Peter Dutton, Sadie Jones, Andrew J Nordin, Raj Naik, Alison Fiander, Gareth Griffiths
- Dacomitinib compared with placebo in pretreated patients with advanced or metastatic non-small-cell lung cancer (NCIC CTG BR.26): a double-blind, randomised, phase 3 trial
- Peter M Ellis, Frances A Shepherd, Michael Millward, Francesco Perrone, Lesley Seymour, Geoffrey Liu, Sophie Sun, Byoung Chul Cho, Alessandro Morabito, Natasha B Leighl, Martin R Stockler, Christopher W Lee, Rafal Wierzbicki, Victor Cohen, Normand Blais, Randeep S Sangha, Adolfo G Favaretto, Jin Hyoung Kang, Ming-Sound Tsao, Carolyn F Wilson, Zelanna Goldberg, Keyue Ding, Glenwood D Goss, Penelope Ann Bradbury, on behalf of the NCIC CTG, Australasian Lung Cancer Trials Group, the NCI Naples Clinical Trials Unit
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