Clinical utility of comprehensive genomic profiling in Japan: Result of PROFILE-F study

Abstract

Introduction Clinical sequencing has provided molecular and therapeutic insights into the field of clinical oncology. However, despite its significance, its clinical utility in Japanese patients remains unknown. Here, we examined the clinical utility of tissue-based clinical sequencing with FoundationOne® CDx and FoundationOne® Heme. Between August 2018 and August 2019, 130 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne® CDx or FoundationOne® Heme. Results The median age of 130 patients was 60.5 years (range: 3 to 84 years), and among them, 64 were males and 66 were females. Major cancer types were gastrointestinal cancer (23 cases) and hepatic, biliary, and pancreatic cancer (21 cases). A molecular tumor board had been completed on all 130 cases by October 31, 2019. The median number of gene alterations detected by Foundation testing, excluding variants of unknown significance (VUS) was 4 (ranged 0 to 21) per case. Of the 130 cases, one or more alterations were found in 123 cases (94.6%), and in 114 cases (87.7%), actionable alterations with candidates for therapeutic agents were found. In 29 (22.3%) of them, treatment corresponding to the gene alteration was performed. Regarding secondary findings, 13 cases (10%) had an alteration suspected of a hereditary tumor. Of the 13 cases, only one case received a definite diagnosis of hereditary tumor. Conclusions Our study showed that clinical sequencing might be useful for detecting gene alterations in various cancer types and exploring treatment options. However, many issues still need to be improved.

Analytical validation and clinical utilization of K-4CARETM: a comprehensive genomic profiling assay with personalized MRD detection

“…Furthermore, we demonstrated clinical usefulness of our assay to identify at least 1 actionable mutations (OncoKB level 1-2) in 38.9% of the clinical samples (74/190). This rate seemed to be higher than other CGP assays applied in other cohorts, such as 12.0% in Ng et al [21], 10.7% in Aoyagi et al [27] and 23.7% in Karol et al [28]. It was likely attributed to the distribution of samples across different cancer types in each cohort.…”

Clinical and diagnostic utility of genomic profiling for digestive cancers: real-world evidence from Japan

“…Moreover, 11.5% of patients had CDx-equivalent genomic alterations, demonstrating the clinical utility of genomic panel testing. A previous study testing advanced solid tumors using FoundationOne CDx or FoundationOne Heme., found one or more alterations in 94.6% and actionable alterations with candidates for therapeutic agents in 87.7% of the cases [9].…”

“…The clinical utility of CGP tests covered by the Japanese public health insurance system has been reported mainly based on clinical aspects, including genomic pro ling in light of pharmacotherapy and other treatments [9,10]. The correlation of genomic pro les with pathological features and signaling pathways involved in cancers has not been examined.…”

First-Line Genomic Profiling in Previously Untreated Advanced Solid Tumors for Identification of Targeted Therapy Opportunities

“…Moreover, because as many as 23 patients had options of evidence-level A MBRT among 71 patients who had not received MBRT, we expected that more patients would benefit from CGP before the SOC. The proportions of MBRT evidence levels observed in this study were similar to those in previous reports, 12,17,33 except a few more patients with evidence-level A MBRT were present in our study than the others. Therefore, the present findings suggest that CGP before the SOC could provide an opportunity for receiving potentially effective treatments.…”