Dacomitinib, a potent irreversible pan-HER kinase inhibitor, has activity in EGFR mutant (mt) lung cancer. BR.26, completed in 2013, compared dacomitinib versus placebo in unselected pts who had received both chemotherapy (1 or 2 lines) and a first-generation EGFR TKI for advanced NSCLC. Dacomitinib pts had significantly improved tumour response rate, PFS, and time to symptom deterioration but not improved survival (OS). A trend towards improved OS was seen in pts with KRAS wildtype (wt) tumours (KRAS unknown in 42%). A prospective economic evaluation was planned for Canadian and Australian pts.
Resource utilization and utility scores (EQ5D-3L) were collected prospectively in 385 trial participants from Canada and Australia. Direct medical costs were applied to resources in 2015 Canadian dollars (CAD) from the Canadian public health care payer perspective. Dacomitinib is not approved for marketing, thus we used a range of plausible drug costs (0-$120/mg). Restricted mean survival time, utility, and costs per arm were calculated, and explored in KRAS wt and EGFR mt subgroups.
Incremental outcomes and costs by treatment arm are shown below. Mean utility scores were similar, although higher in dacomitinib-treated pts with KRAS wt or EGFR mt tumours (range u = 0.41- 0.55). Mean quality-adjusted survival was approximately 1 month longer with dacomitinib in both KRAS wt and EGFR mt subgroups. Direct medical costs excluding dacomitinib were similar between arms. Exploratory estimates of cost-utility ranged from $26,369-$184,701/QALY in KRAS wt, and $2,243-$133,953/QALY in pretreated EGFR mt pts.
Dacomitinib in previously treated, unselected NSCLC may yield minor gains in quality-adjusted survival without increasing other costs of care. Analyses of mutation status by ctDNA are ongoing.Table:
|Incremental mean outcome with dacomitinib over placebo||All patients (n = 385)||KRAS wild type (KRAS known n = 165)||EGFR mutant (EGFR known n = 80)|
|Survival (ΔE, years)||0.0014||0.104||0.129|
|Quality-adjusted survival (ΔE, QALY)||0.011||0.069||0.088|
|Cost (ΔC, 2015 CAD) Set drug price at: $0/mg $40/mg $80/mg $120/mg||$524 $3,944 $7,363 $10,783||$1,829 $5,489 $9,149 $12,809||$199 $4,083 $7,968 $11,853|
Clinical trial identification
Legal entity responsible for the study
Canadian Clinical Trials Group (CCTG)
P. Bradbury: Honorarium from Pfizer and Merck. P. Ellis: In the past two years, received honoraria for talks from Boehringer Ingelheim and Novartis. G. Liu: Honoraria from AstraZeneca, Pfizer, Novartis and Takeda. R. Sangha: Honoraria from: Pfizer, Boehringer Ingelheim, AstraZeneca, Roche, Eli-Lilly, Bristol-Myers Squibb and Merck. M. Boyer: I’ve received Honoraria (paid to my institution) from Pfizer, Boehringer Ingelheim and Astra Zeneca. G. Goss: Honoraria from Pfizer, AstraZeneca, Boehringer Ingelheim, Lilly, Bristol-Myers Squibb, and Celgene. L. Seymour: Pfizer provided funding for the BR.26 trial. N.B. Leighl: Research funding (institution) - Novartis Unrelated CME (not speaker\'s bureau) - travel/honoraria - AstraZeneca, Merck Sharpe Dohme, Pfizer, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.