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

Abstract

IMPORTANCEPrecision oncology using comprehensive genomic profiling (CGP) by next-generation sequencing is aimed at companion diagnosis and genomic profiling. The clinical utility of CGP before the standard of care (SOC) is still not resolved, and more evidence is needed.OBJECTIVETo investigate the clinical utility of next-generation CGP (FoundationOne CDx [F1CDx]) in patients with previously untreated metastatic or recurrent solid tumors.DESIGN, Setting, and ParticipantsThis multicenter, prospective, observational cohort study enrolled patients with previously untreated advanced solid tumors between May 18, 2021, and February 16, 2022, with follow-up through August 16, 2022. The study was conducted at 6 hospitals in Japan. Eligible patients were aged 20 years or older and had Eastern Cooperative Oncology Group performance status of 0 to 1 with previously untreated metastatic or recurrent cancers in the gastrointestinal or biliary tract; pancreas, lung, breast, uterus, or ovary; and malignant melanoma.EXPOSUREComprehensive genomic profiling testing before SOC for advanced solid tumors.MAIN OUTCOMES AND MEASURESProportion of patients with actionable or druggable genomic alterations and molecular-based recommended therapy (MBRT).RESULTSA total of 183 patients met the inclusion criteria and 180 patients (92 men [51.1%]) with a median age of 64 years (range, 23-88 years) subsequently underwent CGP (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]). Data from 172 patients were available for end point analyses. Actionable alterations were found in 172 patients (100.0%; 95% CI, 97.9%-100.0%) and druggable alternations were identified in 109 patients (63.4%; 95% CI, 55.7%-70.6%). The molecular tumor board identified MBRT for 105 patients (61.0%; 95% CI, 53.3%-68.4%). Genomic alterations included in the companion diagnostics list of the CGP test were found in 49 patients (28.5%; 95% CI, 21.9%-35.9%) in a tumor-agnostic setting. After a median follow-up of 7.9 months (range, 0.5-13.2 months), 34 patients (19.8%; 95% CI, 14.1%-26.5%) received MBRT.CONCLUSIONS AND RELEVANCEThe findings of this study suggest that CGP testing before SOC for patients with advanced solid tumors may be clinically beneficial to guide the subsequent anticancer therapies, including molecularly matched treatments.

Clinical genetics in breast cancer

“…Demonstrating the potential utility of such testing, a study in Japan recruited 172 patients with recurrent or previously untreated metastatic solid tumors, 25 of which were primary breast cancer tumors, to undergo next-generation comprehensive genomic profiling. 64 All 172 cases had actionable alterations with 109 of those cases being druggable alterations, and these findings may indicate a theoretical use for FoundationOne-informed treatment.…”

Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series

“…In the clinic, diagnostic tests including FISH and NGS tests such as FoundationOne Cdx can be used to detect MDM2 amplification. 17 , 27 , 28 Analysis of MDM2 overexpression or amplification should be included in molecular analysis of BTC tumors.…”

Serial comprehensive genomic profiling by next‐generation sequencing for patients with metastatic colorectal cancer

“…Recent data on the use of first-line CGP for advanced solid tumors in Japan has prompted interest in earlier use of such technology. 3 If CGP were to move to earlier lines of testing in Japan, what might be the clinical value for testing patients again by CGP after disease progression? We considered metastatic colorectal cancer (mCRC) as a model for two reasons: (1) It is the most registered tumor type with the Japanese Center for Cancer Genomics and Therapeutics (C-CAT), 4 and (2) international clinical practice guidelines recommend testing for the presence of multiple genomic biomarkers prior to treatment for patients with mCRC.…”

“…Recent data on the use of first‐line CGP for advanced solid tumors in Japan has prompted interest in earlier use of such technology. 3 …”