A Pilot Prospective Study of Refractory Solid Tumor Patients for NGS-Based Targeted Anticancer Therapy

Area of Science:

• Oncology
• Genomics
• Personalized Medicine

Background:

• Refractory and metastatic cancers often develop chemotherapy resistance, limiting treatment options.
• Next-generation sequencing (NGS) offers a way to identify specific genetic alterations for targeted therapy.
• Evaluating the clinical utility of NGS in this patient population is crucial.

Purpose of the Study:

• To assess the efficacy and clinical feasibility of NGS-based targeted anticancer therapy.
• To identify actionable genetic alterations in patients with refractory metastatic solid tumors.
• To evaluate treatment responses in patients receiving targeted therapy based on NGS findings.

Main Methods:

• Utilized a gene panel covering 83 cancer-related genes for targeted sequencing.
• Enrolled 25 patients with refractory metastatic solid tumors.
• Assessed treatment effectiveness through follow-up and biological characterization of mutations.

Main Results:

• NGS identified FDA-approved drug-responsive or -resistant alterations in 7 out of 25 patients.
• Three patients (12%) showed partial response to targeted therapy, including crizotinib for ALK-EML4 fusion and everolimus for AKT3 amplification.
• A KRAS A146V mutation, associated with anti-EGFR resistance, was identified and characterized, with the patient responding to bevacizumab.

Conclusions:

• NGS-based targeted therapy can identify actionable alterations in refractory metastatic solid tumors.
• Targeted therapy guided by NGS demonstrated clinical efficacy in a subset of patients.
• NGS testing represents a promising strategy for enhancing the management of refractory solid tumors.