Ida Viller Tuxen (1), Christina Westmose Yde (2), Olga Østrup (2), Morten Mau-Sørensen (1), Eric Santoni-Rugiu (3), Ulrik Lassen (1), Finn Cilius Nielsen (2)
1) Department of Oncology, Rigshospitalet,Copenhagen. 2) Center of Genomic Medicine, Rigshospitalet, Copenhagen.
3) Department of Pathology, Rigshospitalet,Copenhagen.
Advanced technologies can be used to portray genomic alterations (GA) that potentially drive tumor growth. We have established a sequencing and array based pipeline to identify GA to select patients (pts) who might benefit from novel targeted treatments and to enrich the population in phase 1 trials with pts that harbor specific targets.
Materials and methods
Adults with advanced solid tumors referred to a dedicated Phase 1 Unit were offered biopsy for mapping of GA. Three fresh tumors 18 G needle biopsies were taken, two were stored in RNAlater® (Life Technologies) for RNA expression analyses and DNA gene mutation analyses, while one biopsy was formalin-fixed and paraffin-embedded for histopathological analyses to confirm suitability of the material, including the presence of min. 100 tumor cells. SNP-array from tumor and whole exome sequencing (WES) from DNA (tumor and blood) were performed using sequence capture and Illumina sequencing to call tumor specific mutations. WES from blood was used to subtract germline polymorphisms. Expression levels of therapeutic targets were revealed by expression Array and RNA-seq from tumor RNA. A tumor board reviewed results. Pts with specific GA that could be targeted with drugs in development were enrolled in phase 1 trials. Individualized treatment with marketed drugs (Off-label) or non-approved drugs (Named patient program) were offered according to level of existing evidence.
Between May, 2013 and April, 2016, we screened 366 heavily pretreated pts with solid tumors. In 297 pts (81%) a biopsy was taken. In 283 (77%) we achieved sufficient tumor tissue to perform a full genomic profile. An actionable target was identified in 215 pts (75%) out of 283 pts. Mean time from biopsy to reporting of results was 36 days. 153 pts with an actionable target were eligible for treatment. 57 pts (20%) were treated according to the findings of either mutations or RNA expression levels of treatment targets in phase 1 trials (N=39) or Off-label treatment/Named patient program (N=18)
Establishing sequencing and array-based pipeline for enrichment of patients to phase 1 trials is feasible in a Phase 1 Unit