Impact of genomic profiling on the treatment and outcomes of patients with advanced gastrointestinal malignancies

Abstract

The impact of genomic profiling on the outcomes of patients with advanced gastrointestinal (GI) malignancies remains unknown. The primary objectives of the study were to investigate the clinical benefit of genomic-guided therapy, defined as complete response (CR), partial response (PR), or stable disease (SD) at 3 months, and its impact on progression-free survival (PFS) in patients with advanced GI malignancies. Clinical and genomic data of all consecutive GI tumor samples from April, 2013 to April, 2016 sequenced by FoundationOne were obtained and analyzed. A total of 101 samples from 97 patients were analyzed. Ninety-eight samples from 95 patients could be amplified making this approach feasible in 97% of the samples. After removing duplicates, 95 samples from 95 patients were included in the further analysis. Median time from specimen collection to reporting was 11 days. Genomic alteration-guided treatment recommendations were considered new and clinically relevant in 38% (36/95) of the patients. Rapid decline in functional status was noted in 25% (9/36) of these patients who could therefore not receive genomic-guided therapy. Genomic-guided therapy was utilized in 13 patients (13.7%) and 7 patients (7.4%) experienced clinical benefit (6 PR and 1 SD). Among these seven patients, median PFS was 10 months with some ongoing durable responses. Genomic profiling-guided therapy can lead to clinical benefit in a subset of patients with advanced GI malignancies. Attempting genomic profiling earlier in the course of treatment prior to functional decline may allow more patients to benefit from these therapies.

Keywords: Clinical benefit; gastrointestinal malignancies; genomic-guided therapy; genomics; precision medicine.

Figure 1

Mutation frequencies of genes in colorectal, pancreatic, and appendiceal adenocarcinoma.

Figure 2

Flow diagram providing a summary of samples.

Figure 3

Summary of patients treated with genomic‐guided therapy and progression‐free survival. One patient with BRCA2 mutation and metastatic pancreatic cancer recently started irinotecan and cisplatin and was not evaluable.

Figure 4

(A) CA 19‐9 and radiologic response in a patient with metastatic pancreatic cancer found to have BRCA2 mutation and treated with irinotecan and cisplatin; (B) CA 19‐9 and radiologic response in a patient with metastatic pancreatic cancer treated with ALK inhibitors crizotinib and ceritinib; (C) CA 19‐9 and radiologic response in a patient with unresectable cholangiocarcinoma treated with pembrolizumab. Pre and Post indicate pretherapy and posttherapy scans. Arrows mark the index lesions that were most easy to demonstrate and compare on the scans.