103IN - Is the Neoadjuvant Model an Accelerated Path Towards Breast Cancer Treatment Tailoring? Experience of the Neoaltto Trial

Abstract

ABSTRACT Around 5% of oncology agents in the development pipeline receive regulatory approval. This procedure is very long and expensive, which results in delaying the availability of effective therapies to patients. Furthermore, one available, they are provided at a considerably high cost to compensate for the exhaustive development process. What is more frustrating is that after such a process we still have a crude idea on the subsets of patients who will “truly” benefit a given agent. Hence, there is a need to adopt innovative strategies to accelerate drug development in a more efficient and targeted way. In breast cancer (BC), the neoadjuvant setting emerge as an excellent opportunity to incorporate biomarkers within the drug development process, taking the advent of the presence of a robust short term surrogate endpoint, like pathological complete response (pCR). It also allows interrogating the effect of novel therapies on BC biology, via the collection of samples pre and post therapy. These advantages would help in accelerating drug and biomarker development via the conduction of trials that are relatively small in size and short in duration. This would possibly have a positive impact on the health-care economics dimension as well. NeoALTTO is a phase 3 trial, which included 455 patients with HER2-positive non-metastatic BC. Patients randomized to lapatinib and trastuzumab in combination with paclitaxel had nearly double the pCR rate compared to those randomized to paclitaxel with either drug alone. A similar trial but in the adjuvant setting (ALTTO) including nearly 8,000 patients has recently completed accrual. If the higher pCR rate in the NeoALLTO trial translated into improved long term outcome and this was confirmed in ALTTO, this could represent an important milestone in the way we develop targeted agents in BC, and hence conducting huge trials like ALTTO might not be needed in the future. The NeoALTTO trial also had an extensive translational research and molecular imaging programs with their results expected to be available very soon. It is fascinating to see the tremendous amount of information that can be generated and the possible impact this might have on patient care, with a study that included less than 500 patients. Hence, this model encourages the adoption of the neoadjuvant setting in investigating novel agents/treatment strategies, which could represent a smart, fast and cheap way in obtaining regulatory approval of effective agents. Disclosure All authors have declared no conflicts of interest.