Abstract
OBJECTIVE: Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient's survival. In gastrointestinal (GI) malignancies, the concept of personalized medicine (PM) was not investigated so far. The aim of this prospective study was to evaluate the efficacy of a personalized treatment in GI patients who failed standard treatment. METHODS: Out of the original prospective clinical phase II EXACT trial, 21 (38%) GI cancer patients who had no further treatment options were identified. A molecular profile (MP) via a 50 gene next generation sequencing (NGS) panel in combination with immunohistochemistry (IHC) was conducted using real-time biopsy tumor material. Results were discussed by a multidisciplinary team (MDT) to translate the individual MP in an experimental treatment. RESULTS: Of the 55 patients originally included in the EXACT trial, 21 (38%) suffered from GI malignancies. The final analysis showed that 15 (71%) patients had experienced a longer progression-free survival (PFS) upon experimental targeted treatment (124 d, quartiles 70/193 d), when compared with the PFS achieved by the previous conventional therapy (62 d, quartiles 55/83 d) (P=0.014). Thirteen (62%) patients receiving targeted treatment experienced a disease control according to Response Evaluation Criteria in Solid Tumors (RECIST). Median overall survival (OS) from the start of experimental therapy to time of censoring or death was 193 d (quartiles 115/374 d). CONCLUSIONS: PM was not investigated in GI malignancies so far in a prospective trial. This study shows that treatment based on real-time molecular tumor profiling led to a superior clinical benefit, and survival as well as response was significantly improved when compared with previous standard medications.