Abstract 139P
Background
Randomized clinical trials investigate general and representative patient populations, yet clinical decisions increasingly depend on the characteristics of individual patients. In this exploratory analysis of the ExteNET trial, we tested the efficacy of continuing with 1 year of neratinib after completing adjuvant trastuzumab therapy in breast cancer patients at high risk of relapse.
Methods
For the purpose of our analysis, we tested invasive disease-free survival (iDFS) at 2 and 5 years in hormone receptor-positive BC patients included in ExteNET population after Amendment 3, which ruled out patients with stage I/ node negative disease, and those with pCR after neoadjuvant therapy, in order to enrich the population with patients at higher risk of recurrence.
Results
Out of 1334 HER2+/HR+ BC patients initially recruited by ExteNET, 1056 (79%) qualified as at high-risk according to baseline disease characteristics. Neratinib reduced the relative risk for 2-year iDFS by 48% compared with placebo (HR 0.52, 95%CI 0.32-0.84). This advantage was confirmed with the 5-year iDFS analysis which was reduced by 39% (HR 0.61, 95%CI 0.42-0.88) (Table). Notably, no significant interaction between risk categories, hormone receptor status, and use of neratinib was observed for both endpoints, suggesting that the benefit derived by high risk patients resembled that derived by the whole ExteNET study population. Table: 139P
| Number of events | Absolute difference (%) | Hazard Ratio (95% CI) | ||
| Neratinib (n=531) | Placebo (n=525) | |||
| 2-year iDFS | 25 | 49 | 4.7 | 0.52 (0.32-0.84) |
| 5-year iDFS | 47 | 76 | 5.6 | 0.61 (0.42-0.88) |
Conclusions
Although descriptive in nature, our results show that patients with HER2+/HR+ breast cancer with large primary tumors, lymph node involvement, and lack of response to neoadjuvant therapy are likely to derive meaningful and sustained benefit over time when treated with neratinib after standard trastuzumab-based therapy.
Clinical trial identification
ExteNET: NCT00878709.
Editorial acknowledgement
Legal entity responsible for the study
Pierre Fabre.
Funding
PUMA Biotechnology.
Disclosure
S. Di Cosimo: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre. F. Caprari, E. Dapretto, J. Trouiller, R. Valenti: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre. All other authors have declared no conflicts of interest.