Abstract 5147: Clinical benefit of molecularly-guided treatment strategies on progression free survival in patients with advanced gastrointestinal malignancies
Authors: Buzard Blake , Gonser Tyler , Hinrichsen Melissa , Amallraja Anu , Williams Kirstin , De Pradip , Leyland-Jones Brian , Elsey Rachel , Meissner Tobias , Williams Casey 
Published: August 2019

Introduction: Despite many advances, the treatment for most patients with advanced solid tumors in the abdomen continues to be a clinical challenge. The purpose of our study was to evaluate the clinical benefit of molecularly-guided treatment strategies on progression free survival in patients with advanced gastrointestinal malignancies.

Materials and Methods: We performed a retrospective chart review of 112 patients with advanced (&gt;90% stage IV) gastrointestinal cancer (n=60 colon, n=21 pancreas, n=10 cholangio, n=8 esophageal, n=13 others) that underwent targeted DNA sequencing of 343 genes and assessed mutations, treatments and outcomes. We compared evidence-based standard of care therapy to molecularly-guided treatment on progression free survival time pre- and post-sequencing. We further assessed KRAS mutational status on patient outcomes, as well as potential correlation between time to molecularly-guided treatment and patient outcomes.

Results: Out of 112 patients sequenced and presented to our molecular tumor board, 50% received molecularly-guided treatment. Most frequent molecularly-guided regimens included the addition of either a MEK and/or an mTOR inhibitor. The MEK inhibitor Trametinib was recommended for 58/112 patients, due to activating mutations in the RAS-MAPK pathway (46 of all patients were KRAS mutated), and 27/58 patients received Trametinib. The mTOR inhibitor Everolimus was recommended for 32/112 patients due to PI3K-mTOR pathway activating mutations, with 18/32 patients receiving Everolimus. Doublet therapy of Trametinib and Everolimus was given to n=13 patients, with n=5 patients receiving Everolimus only and n=14 patients receiving Trametinib only as targeted therapy. Comparing patients for whom either Trametinib and/or Everolimus was given after recommendation with patients who did not receive the recommendation, we did not find a difference in outcome. However, overall progression free survival (PFS) increased for patients receiving molecularly-guided treatment after sequencing compared to patients who received standard treatment, by an average PFS of 9 months. Patients who did not receive molecularly-guided therapy until later in their disease course had poorer outcomes compared to those who received it earlier in their treatment.

Conclusions: Molecularly-guided therapy is an emerging treatment strategy for patients with gastrointestinal cancers. Our work showed that progression free survival was increased in patients who received molecularly-guided therapy compared to standard treatment. More research is needed to assess any direct correlations between most genetic mutations and clinical outcomes.

Citation Format: Blake Buzard, Tyler Gonser, Melissa Hinrichsen, Anu Amallraja, Kirstin Williams, Pradip De, Brian Leyland-Jones, Rachel Elsey, Tobias Meissner, Casey Williams. Clinical benefit of molecularly-guided treatment strategies on progression free survival in patients with advanced gastrointestinal malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5147.