Precision medicine seeks to identify the best treatment for each individual based on the patient’s unique characteristics. This approach could allow doctors and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people. This new paradigm needs significant changes in clinical trial conduct: a small number of patients that meet very specific protocol requirements.

The PRECISION (The Belgian Molecular Profiling Program of Metastatic Cancer for Clinical Decision and Treatment Assignment) program comprises two initiatives and is led by the Belgian Society of Medical Oncology (BSMO). PRECISION 1 aims to establish an inter-platform cooperation and sequencing quality control and examine the feasibility and efficiency of using information coming out of this effort to direct patients to existing genotype-based clinical trials. The trial will serve as the basis fort the creation of a clinico-genomic database suitable for data sharing and the generation of research questions. PRECISION 2 will organize exploratory phase 2 studies in genotypes not covered by available validated treatments or ongoing genotype-based clinical trials. The establishment of a national strategy of systematic genomic characterization of patients with metastatic cancer could foster the implementation of novel genotype driven trials and make the Belgian centers more attractive for such new development trials with new targeted drugs or other genotype-driven treatments by having a pool of patients that have been genotyped. Equally for the patients this creates an opportunity to benefit more easily from inclusion in trials with new potentially high impact drugs.

At this moment one PRECISION 2clinical study has been opened:

An explorative phase II, open label study of afatinib in advanced cancer carrying an EGFR, a HER2 or a HER3 mutation followed by the addition of paclitaxel to afatinib at disease progression

The principal Investigator of the study isDr Lore Decoster, MD (Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium)

The sponsor is the BSMO

The site investigators are: P Aftimos (IJ Bordet), S Rottey (UZ Gent), J Collignon (CHU Liège), C Rolfo (UZA), J-P Machiels (Les CliniquesUniversitaires St Luc), G Berchem (CH Luxembourg)

Afatinib was approved as monotherapy in Belgium to treat patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor reception (EGFR) mutations. This drug is a selective and irreversible erbB family blocker, which inhibits EGFR, HER2 and HER4. In addition, preclinical activity with afatinib against HER3 mutations has been described [1]. In cancers, other than NSCLC, EGFR mutations can be found in 1.6% [2]. HER2 mutations are present in 1-2% of lung adenocarcinoma and have also been described in 1-5% of breast cancers, ovarian cancers and colorectal cancer, bladder cancers and gastric cancers [3].

The current study has two major objectives:

1. Building evidence on drug efficacy of afatinib in cancers harboring either an EGFR or a HER2 or a HER3 mutation in which it would be difficult to obtain such evidence due to the rarity of the mutation.

2. Facilitating access to a potentially high impact drug for patients with EGFR mutations, excluding non-squamous NSCLC, HER2 or HER3 mutations in their tumors

Planned number of patients to be included: 87

References:

[1] Umelo I, Noeparast A, Chen G, et al. Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer. Oncotarget 2016;19:3068-83

[2] Wheler JJ, Falchook GS, Tsimberidou AM, Hong DS, Naing A, Piha-Paul SA, et al. Aberrations in the epidermal growth factor receptor gene in 958 patients with diverse advanced tumors: implications for therapy. Ann Oncol 2013;24:838-42.

[3] Herter-Sprie GS, Greulich H, Wong KK. Activating mutations in ERBB2 and their impact on diagnostics and treatment. Front Oncol 2013;23:86.