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.…”

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.…”

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer

“…In Japan, approximately 22.3% of patients who underwent CGP in all solid tumors were treated with molecularly targeted therapy as the recommended treatment [4], but few were reported with regard to gynecological malignancies [7].…”

“…Since the health insurance approved to cover CGP, the number of CGP exams performed has been increasing [2][3][4][5][6]; however, the status of multigene panel testing in gynecological malignancies and the clinicopathological characteristics of the patients remain insu ciently reported [7,8]. Thus, this study aimed to summarize the results of the CGP examination at our hospital (Designated Core Hospital for Cancer Genomic Medicine) to investigate its usefulness as a potential treatment option for advanced and recurrent gynecologic cancers.…”