Slide 1: Neratinib after trastuzumab-based adjuvant therapy in early-stage HER2+ breast cancer: 5-year analysis of ExteNET
Oral presentation #149O Neratinib after trastuzumab-based adjuvant therapy in early-stage HER2+ breast cancer: 5-year analysis of the phase III ExteNET trial Miguel Martin,1 Frankie A. Holmes,2 Bent Ejlertsen,3 Suzette Delaloge,4 Beverly Moy,5 Hiroji Iwata,6 Gunter von Minckwitz,7 Stephen K.L. Chia,
Slide 2: Disclosures
Disclosures • Miguel Martin has received: – Speaker´s honoraria from Roche/Genentech, Novartis, Amgen, AstraZeneca, Pfizer, PharmaMar and Lilly – Research grants from Roche and Novartis 2
Slide 3: Funding
Funding • ExteNET was sponsored by Wyeth, Pfizer and Puma Biotechnology
Slide 4: Background
Background • Adjuvant trastuzumab added to standard chemotherapy significantly improves overall survival in women with early HER2+ breast cancer1-3 • Despite the use of trastuzumab-based therapy, 15 to 24% of patients have breast cancer recurrences after a median of 8 to 11 years1,3 • New adjuvant t
Slide 5: ExteNET: study design
ExteNET: study design Part A Part B Part C • HER2+ breast cancer 2-year follow-up for iDFS 5-year follow-up for iDFS – IHC 3+ or ISH amplified Neratinib x 1 year Randomization (1:1) (locally determined) Overall survival – Prior adjuvant trastuzumab + 240 mg/day chemotherapy – Lymph node +/–, or resi
Slide 6: ExteNET: study analysis
ExteNET: study analysis Part A (Primary analysis) • 2-year analysis for all efficacy endpoints in ITT, except overall survival • 2-year iDFS rate 93.9% for neratinib vs 91.6% for placebo (HR 0.67, P=0.0091)1 • Performed in July 2014 Part B • Descriptive 5-year analysis for all efficacy endpoints, ex
Slide 7: ExteNET: results
ExteNET: results • Between July 2009 and October 2011, 2840 women were randomly assigned to study treatment (neratinib, n=1420; placebo, n=1420) – At the cut-off date, 2117 patients (76.0%) had re-consented to the collection of further data (neratinib, n=1028; placebo, n=1089) 7
Slide 8: 5-year analysis: baseline characteristics
5-year analysis: baseline characteristics Intent-to-treat population Re-consented population Neratinib Placebo Neratinib Placebo (n=1420) (n=1420) (n=1028) (n=1089) Median age, years (range) 52 (25–83) 52 (23–82) 52 (25–83) 53 (24–81) Nodal status, n (%)a Negative 335 (24) 336 (24) 216 (21) 261 (24)
Slide 9: 5-year analysis: iDFS events by site
5-year analysis: iDFS events by site Neratinib Placebo Event site (n=1420) (n=1420) Any iDFS event, n (%) 116 (8.2) 163 (11.5) Distant recurrence 91 (6.4) 111 (7.8) Local/regional invasive recurrence 12 (0.8) 35 (2.5) Invasive ipsilateral breast cancer recurrence 5 (0.4) 7 (0.5) Invasive contralater
Slide 10: 5-year analysis: iDFS
5-year analysis: iDFS 100 97.9% 94.3% 92.2% Invasive disease-free survival (%) 95.5% 91.2% 90.2% 90 91.7% ∆ 2.4% 90.2% ∆ 2.6% 89.1% 87.7% ∆ 2.0% ∆ 2.1% 80 ∆ 2.5% 70 HR (95% CI) = 0.73 (0.57–0.92) 60 Two-sided P = 0.008 50 Treatment Neratinib Placebo 0 0 6 12 18 24 30 36 42 48 54 60 Months after rand
Slide 11: 5-year analysis: by endpoint
5-year analysis: by endpoint Estimated event-free rate,a % Neratinib Placebo Hazard ratiob P valueb Endpoint (n=1420) (n=1420) (95% CI) (2-sided) Invasive disease-free survival 90.2 87.7 0.73 (0.57‒0.92) 0.008 Disease-free survival with DCIS 89.7 86.8 0.71 (0.56‒0.89) 0.004 Distant disease-free surv
Slide 12: 5-year subgroup analysis: iDFS
5-year subgroup analysis: iDFS Hazard ratio No. of events Subgroup No. of patients (95% CI) Neratinib vs. Placebo HR (95% CI) All patients 2840 116 vs. 163 0.73 (0.57–0.92) Region of the World North America 996 40 vs. 46 0.84 (0.55–1.28) W. Europe, AUS & S. Africa 1019 43 vs. 63 0.78 (0.52–1.14) Asi
Slide 13: 5-year subgroup analysis: iDFS (cont'd)
5-year subgroup analysis: iDFS (cont’d) Hazard ratio No. of events Subgroup No. of patients (95% CI) Neratinib vs. Placebo HR (95% CI) Race Asian 385 14 vs. 26 0.55 (0.28–1.04) White 2300 99 vs. 130 0.77 (0.59–1.00) Black or other 155 3 vs. 7 0.61 (0.13–2.21) T-stage at diagnosis T1 899 20 vs. 25 0.
Slide 14: iDFS by hormone receptor status
iDFS by hormone receptor status HR-positive subgroup HR-negative subgroup 100 98.1% 100 97.5% 95.4% 93.6% 92.6% 92.8% 90.8% 89.9% 90 96.1% 91.2% 90 94.7% 88.9% Invasive disease-free survival (%) Invasive disease-free survival (%) 91.7% 91.8% 90.4% 88.8% 89.8% 86.8% 89.3% 88.5% 80 80 70 70 HR (95% CI
Slide 15: ExteNET: long-term safety and HRQoL
ExteNET: long-term safety and HRQoL • Serious adverse events reported after treatment discontinuation showed no evidence of: – Long-term toxicity, specifically increased symptomatic cardiac toxicity or second primary malignancies, with neratinib versus placebo – Late-term consequences from neratinib
Slide 16: ExteNET: conclusions
ExteNET: conclusions • The 5-year analysis of the ExteNET trial confirms sustained benefit with extended adjuvant neratinib: – 2.5% absolute benefit in intent-to-treat population (HR=0.73; P=0.008) – 4.4% absolute benefit in HR-positive cohort (HR=0.60; P=0.002) • No evidence of long-term toxicity (
Slide 17: Acknowledgements
Acknowledgements • We would like to acknowledge the contribution of the Independent Data Monitoring Committee • We would also like to thank the investigators and patients involved in the ExteNET trial 17