NEW YORK – Next-generation sequencing (NGS) or whole-exome sequencing of tumor and normal samples from advanced gastrointestinal (GI) cancer patients helped identify individualized treatment options and pathogenic germline variants associated with cancer risk, according to a study published last week in the Journal of Clinical Oncology: Precision Oncology.
The retrospective, open-label, histology-agnostic analysis, led by Michael Bitzer of Eberhard-Karls University in Tübingen, Germany, focused on a group of 96 patients who had been referred to an interdisciplinary molecular tumor board (MTB) at the University Hospital Tübingen between April 2016 and February 2018. These patients had been diagnosed with different GI cancers, including colorectal cancer, pancreatic cancer, biliary tract cancer, hepatocellular carcinoma, upper GI tract cancer, and neuroendocrine tumors.
Tumor/normal analysis via NGS or WES revealed clinically significant germline variants, classified as pathogenic, likely pathogenic, or pharmacogenetic, in 19 patients.
After the MTB identified relevant targetable molecular alterations, 41 patients received personalized treatment recommendations, including drugs available via clinical studies or matched on-label, off-label, or experimental treatment options. The 43 percent of patients who received these recommendations highlighted that for four out of 10 patients additional therapy options existed beyond established treatment, noted the study authors.
Ultimately, 25 patients ended up receiving treatment according to these recommendations, of which 20 were evaluable for overall survival and 19 were evaluable for progression-free survival.
The median progression-free survival for all treated and evaluable patients was 2.8 months and the median overall survival of all treated patients was 5.2 months. In an effort to better understand the treatment benefit to patients, the study authors performed Kaplan-Meier analysis of progression-free survival and overall survival, comparing those who achieved stable disease and had a partial response on an MTB recommended treatment against those who progressed on treatment.
Ultimately, six patients achieved stable disease, three patients reached partial response, and 11 patients had tumor progression regardless of treatment. The disease control rate was 45 percent. Patients who reached stable disease or had a partial response showed a statistically significant longer median progression-free survival of 7.8 months versus 2.2 months in the progressive disease group and overall survival of 19 months versus 3.8 months, respectively.
"The difference in overall survival of greater than 14 months in our cohorts, compared with patients with progressive disease as best response, is remarkable," wrote the study authors, acknowledging that the results should be interpreted with some degree of caution until they can be confirmed in larger patient populations.
Ultimately, the authors said, they were able to show that integrating NGS into clinical practice allowed them to identify an unexpectedly high number of germline variants and unique treatment options for patients with GI cancers. Accordingly, "the inclusion of additional complex diagnostic procedures and the integration of individualized tumor characterization at an earlier disease stage might substantively enhance the treatment opportunities in everyday clinical practice for these patients in the near future."