Clinical Application of Targeted Deep Sequencing in Solid-Cancer Patients and Utility for Biomarker-Selected Clinical Trials

Abstract

This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase.

Precision oncology: East meets West

“…A recent study evaluating a South Korean population from the Samsung Medical Center reported that a total of 55 of 418 (12.0%) patients harbored a biomarker that led to subsequent rational allocation to a clinical trial. 11 The most commonly mutated oncogenes in the overall cohort included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%) and KIT (3%) aberrations, while the most frequently mutated tumor suppressor genes included TP53 (40%), which again parallels other precision oncology studies. The expected higher prevalence of EGFR aberrations in Asian patients with lung cancer was confirmed in the IMAC study Specifically, 15 of 48 (31%) lung tumors harbored at least one mutation in the EGFR domain.…”

“…This 8% patient match rate is similar to the 5–11% match rates reported in other studies. A recent study evaluating a South Korean population from the Samsung Medical Center reported that a total of 55 of 418 (12.0%) patients harbored a biomarker that led to subsequent rational allocation to a clinical trial . The most commonly mutated oncogenes in the overall cohort included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%) and KIT (3%) aberrations, while the most frequently mutated tumor suppressor genes included TP53 (40%), which again parallels other precision oncology studies.…”

Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial

“…To our knowledge, this is the first and largest study to use an umbrella platform trial design with preplanned genomic biomarker analyses to assign patients with advanced gastric cancer to molecularly matched therapies. Using a centrally standardized molecular screening protocol, we enrolled 772 patients with gastric cancer and successfully performed tissue analysis for more than 90% (92.6%) of the patients as reported in our previous studies (28,31). In this study, we demonstrated that when comprehensive molecular screening is linked to seamless immediate access to parallel matched trials, nearly 1 in 7 (14.7%) patients with advanced gastric cancer can receive biomarker-assigned drug treatment.…”

“…Genomic variations are increasingly being utilized as reliable biomarkers for predicting clinical response to therapy for gastric cancer (27)(28)(29). To identify genomic variants that significantly correlate with clinical response, we compared the maximal tumor burden change per RECIST 1.1 against single genomic alterations ( Fig.…”

“…The MTB had the responsibilities of scientific validation, prioritization of identified molecular aberrations, and providing guidance on the suitable biomarker-driven experimental arm under the umbrella trial. The process time between biopsy and molecular results was set as 21 to 30 days from our previous study (28,31). If multiple targets were simultaneously detected in a single patient, the following prioritization was used for patient assignment based on known drivers: (i) PIK3CA mutation/amplification; (ii) RAS mutation/amplification or MEK signature; (iii) MET amplification; (iv) TP53 mutation; (v) RICTOR amplification; (vi) TSC2 null; (vii) MET overexpression by IHC 3+; and (viii) if none of the above biomarkers were present, patients were allocated to the biomarker-negative arms AZD6738/paclitaxel, capivasertib/ paclitaxel, phase I portion of docetaxel/savolitinib, other clinical trials, or conventional treatment.…”