Meeting
2014 ASCO Annual Meeting
NCIC CTG BR.26: A phase III randomized, double blind, placebo controlled trial of dacomitinib versus placebo in patients with advanced/metastatic non-small cell lung cancer (NSCLC) who received prior chemotherapy and an EGFR TKI.
Authors
Peter Michael Ellis
Juravinski Cancer Centre, Hamilton, ON, Canada
Peter Michael Ellis , Geoffrey Liu , Michael Millward , Francesco Perrone , Frances A. Shepherd , Sophie Sun , Byoung Chul Cho , Alessandro Morabito , Martin R. Stockler , Rafal Wierzbicki , Victor Cohen , Normand Blais , Randeep S. Sangha , Adolfo G. Favaretto , Jin Hyoung Kang , Carolyn F. Wilson , Joseph O'Connell , Keyue Ding , Glenwood D. Goss , Penelope Ann Bradbury
Organizations
Juravinski Cancer Centre, Hamilton, ON, Canada, Ontario Cancer Institute, Princess Margaret Cancer Centre, Toronto, ON, Canada, Australasian Lung Cancer Trials Group, Sydney, Australia, Clinical Trials Unit, National Cancer Institute, Napoli, Italy, Princess Margaret Hospital Cancer Centre, Toronto, ON, Canada, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC, Canada, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, National Cancer Institute, G.Pascale Foundation, Napoli, Italy, NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia, R. S. MacLaughlin Durham Regional Cancer Centre, Oshawa, ON, Canada, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada, Cross Cancer Centre, Edmonton, AB, Canada, Istituto Oncologico Veneto, Padua, Italy, Division of Medical Oncology, Department of Internal Medicine,Seoul St.Mary's Hospital, The Catholic University, Seoul, South Korea, NCIC Clinical Trials Group, Kingston, ON, Canada, Pfizer Oncology, New York, NJ, NCIC Clinical Trials Group, Queen's University, Kingston, ON, Canada, Division of Medical Oncology, University of Ottawa, Ottawa, ON, Canada
Research Funding
Pharmaceutical/Biotech Company
Background: Dacomitinib (D) is an irreversible pan-HER inhibitor with evidence of activity in previously treated NSCLC patients (pts). Methods: BR26, a phase III randomized double blind placebo (P) controlled trial of D (45mg daily oral) vs P in NSCLC pts after one to three lines of chemotherapy and an EGFR TKI, randomized pts 2:1 to D or P. Response was assessed at 4, 8 then every 8 weeks during treatment. The primary endpoint was overall survival (OS). Secondary endpoints included OS in pts with KRAS wild type (WT) NSCLC, progression free survival (PFS), response rate (RR), toxicity, quality of life, biomarker analyses and resource utilization. Results: 720 pts were randomized: median age 64 yrs (range 32-90), male 51%, PS 0/1 75%, adenocarcinoma 73%, never smokers 36%. D did not improve OS compared with P (median OS 6.8m v 6.3m, HR 1.0, 95%CI 0.83-1.21, p=0.99). There was significant improvement in PFS favoring D (median PFS 2.7m v 1.4m, HR 0.66, 95%CI 0.55 – 0.79, p<0.0001). The RR was 7% v 1%, p=0.001. EGFR /KRAS status were known in 531/418 pts, respectively. The effect of D on OS was similar in pts with EGFR WT and EGFR mutation positive NSCLC (HR 0.93 vs 0.98, interaction p=0.69). The effect of D on OS appeared to differ by KRAS status: improving OS in pts with KRAS WT tumors (7.0m v 5.2m, HR 0.79, 95%CI 0.61 – 1.03), but worsening OS in pts with KRAS mutation positive NSCLC (5.8m v 8.3m, HR 2.1, 95%CI 1.05 – 4.22, interaction p=0.08). Pts on D had significantly longer time to deterioration of cough (p<0.0001), dyspnea (p=0.049) and pain (p=0.041). Pts treated with D vs. P [%] experienced more diarrhea (80 vs. 20), acneiform rash (60 vs. 10), oral mucositis (43 vs. 3), paronychia (30 vs. 0), dry skin (36 vs. 11), nausea/vomiting (36/28 vs. 25/16). Systemic therapy use after PD was 37% in pts. on D vs. 41% on P. Conclusions: D has activity in heavily pretreated pts with NSCLC. Although there was no improvement in OS, BR26 demonstrated a significant improvement in RR, PFS and time to symptom deterioration, and a trend to improved OS in pts with KRAS WT NSCLC. Further evaluation of D in biomarker defined subgroups appears warranted. Clinical trial information: NCT01000025.
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Abstract Details
Session Type
Poster Highlights Session
Session Title
Lung Cancer - Non-small Cell Metastatic
Track
Lung Cancer
Sub Track
Metastatic Non–Small Cell Lung Cancer
Clinical Trial Registration Number
NCT01000025
Citation
J Clin Oncol 32:5s, 2014 (suppl; abstr 8036^)
DOI
10.1200/jco.2014.32.15_suppl.8036
Abstract #
8036^
Poster Bd #
51
Abstract Disclosures
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