Comprehensive genomic profiling before the first-line setting versus after the completion of standard of care in patients with previously untreated advanced solid tumors: The prospective FIRST-Dx study.
Authors: Matsubara Junichi , Mukai Kumi , Yoshioka Masahiro , Kage Hidenori , Oda Katsutoshi , Kudo Ryo , Ikeda Sadakatsu , Ebi Hiromichi , Muro Kei , Hayashi Ryuji , Tokudome Nahomi , Yamamoto Nobuyuki , Muto Manabu 
Published: June 2023

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Background: Precision oncology using the comprehensive genomic profiling (CGP) test by next-generation sequencing has been introduced into clinical practice. In Japan, only 6.8% of patients accessed the precision treatment because it is only indicated after standard of care (SoC). FoundationOne CDx (F1CDx) is the software as a medical device for the detection of actionable and druggable genomic alterations in 324 genes. F1CDx has the function of both CGP test and companion diagnostics (CDx). Therefore, F1CDx could be ideally used in the early stages of treatments. In this study, we investigated the clinical utility of F1CDx in previously untreated patients with metastatic or recurrent solid tumors. Methods: We conducted a multi-institutional, prospective study in six hospitals in Japan (FIRST-Dx study). Chemotherapy-naïve adult patients with advanced solid tumor (GI, Lung, Breast, GYN, Melanoma) and ECOG performance status of 0-1 were enrolled. Primary endpoint was the ratio of patients with actionable mutation. Secondary endpoints were the ratio of patients with druggable mutation, molecular-based recommended therapy (MBRT), gene alteration with CDx, CGP success rate, and patients who actually received MBRT. Results: 183 patients were enrolled between May 2021 and February 2022, 180 patients with median (range) age 64 (23-88) years underwent F1CDx test (92 men, lung [n=28], colon/small intestine [n=27], pancreas [n=27], breast [n=25], biliary tract [n=20], gastric [n=19], uterus [n=12], esophagus [n=10], ovary [n=6], and skin melanoma [n=6]). 175 tests were successful (CGP success rate: 97%), and 172 patients were evaluable for endpoint analyses with follow-up through July 2022. Actionable and druggable cancer genomic alterations were found in 172 patients (100.0% [95% CI: 97.9-100.0%]) and 109 patients (63.4% [95% CI: 55.7-70.6%]), respectively. MBRT determined by molecular tumor board was found in 105 patients (61.0% [95% CI: 53.3-68.4%]). Genomic alterations included in the CDx list of F1CDx were found in 49 patients (28.5% [95%CI: 21.9-35.9%]) in the tumor-agnostic setting. After a median follow-up of 7.9 months, 34 patients (19.8 % [95%CI: 14.1-26.5%]) actually received MBRTs. Twenty-six patients received evidence level A MBRT, two received evidence level B MBRT, and six received evidence level C MBRT. Conclusions: We showed that 61% of the patients with previously untreated advanced cancer had MBRTs found by F1CDx and 20% of them actually received MBRTs early in their disease course. CGP test before SoC for advanced solid tumors could provide better opportunities for receiving MBRTs than after completion of SoC. Our data would recommend expanded approval with respect to the timing of CGP test for patients with previously untreated advanced solid tumors. Clinical trial information: UMIN000042408 .