CGP Testing Before Standard of Care May Help Guide Anticancer Therapies


Among 172 patients with untreated advanced solid tumors, all of them had actionable alterations, and 109 had druggable alterations.

When treating patients with advanced solid tumors, conducting comprehensive genomic profiling (CGP) tests prior to administering standard of care (SOC) could provide clinical advantages by helping select the appropriate subsequent anticancer treatments, according to a study published in JAMA Network Open.

“The findings of this study suggest that clinical benefits of comprehensive genomic profiling, which is currently limited to patients with cancer refractory to standard therapies in Japan, can be expanded to patients with previously untreated metastatic or recurrent solid tumors,” the study authors said.

The cancers examined included tumors of gastrointestinal, pancreatic, biliary tract, lung, breast, gynecologic, and melanoma origin. According to the authors, CGP testing could provide patients with these untreated metastatic or recurrent solid tumors with the chance to receive highly effective molecular-based recommended therapy (MBRT) early in the disease progression, based on these findings.

“The use of CGP tests was reimbursed by the National Health Insurance in 2019 in Japan as well as in the US and Europe,” the authors explained. “However, the indication in Japan is limited to patients with advanced solid tumors who had completed standard treatment or rare cancers that have no standard treatment, and CGP cannot be used before the initiation of systemic therapy, even though there are no timing restrictions on this indication in other countries. Thus, the full potential of CGP is not used.”

Between May 18, 2021, and February 16, 2022, the authors conducted a multicenter, prospective, observational cohort study at 6 hospitals in Japan. The study included patients 20 years and older with previously untreated advanced solid tumors in the gastrointestinal or biliary tract; in the pancreas, lung, breast, uterus, or ovary; or with malignant melanoma. Patients were eligible if they had an Eastern Cooperative Oncology Group performance status between 0 and 1, and follow-up was conducted until August 16, 2022.

The study included 180 patients who underwent CGP with a next-generation CGP, FoundationOne CDx (F1CDx). The group was 51.1% men and the median age was 64 years, ranging from 23 to 88 years. Of this group, 28 patients had a tumor originating in the lung, 27 in the small intestine, 27 in the pancreas, 25 in the breast, 20 in the biliary tract, 19 in the stomach, 12 in the uterus, 10 in the esophagus, 6 in the ovary, and 6 patients had skin melanoma.

The researchers defined alterations identified in the sections of biomarker findings, genomic findings, and genomic findings without any available therapeutic or clinical trial options in the F1CDx test report as actionable cancer genomic alterations. Alterations with therapeutic drug options were classified as druggable cancer genomic alterations, while alterations associated only with therapeutic resistance—like RAS mutations in colorectal cancer resistant to anti-EGFR antibodies—were not included in the druggable alterations category.

End point analyses were performed using data from 172 patients. Actionable alterations were found for all 172 of these patients (95% CI, 97.9%-100.0%), and druggable alternations were identified in 109 (63.4%) patients (95% CI, 55.7%-70.6%). After excluding the KRAS/NRAS alterations in colon cancer with only therapeutic resistance, the 3 most frequently altered genes were BRAF in skin melanoma, PIK3CA in breast cancer, and ERBB2 in gastric cancer.

The authors also identified MBRT for 105 (61.0%) patients using the molecular tumor board (95% CI, 53.3%-68.4%), and found genomic alterations from the F1CDx companion diagnostics list in 49 (28.5%) patients in a tumor-agnostic setting (95% CI, 21.9%-35.9%). Evidence A, B, C, and D level MBRT was suggested to 49, 3, 24, and 29 patients, respectively. After a median follow-up of 7.9 months, 34 (19.8%) patients received MBRT (95% CI, 14.1%-26.5%), with 26 of these patients receiving evidence A level MBRT.

“These findings may support the modification of the insurance coverage in Japan of CGP from the last line to prior-to-initiation of the primary treatment in patients with metastatic or recurrent solid tumors,” the authors said. “The genomics-guided oncology using CGP testing before SOC for patients with advanced solid tumors may be the first step for future advances in precision oncology.”

The authors noted multiple limitations, including the short follow-up period of 7.9 months, which they said hinders accurate determination of overall survival. To address this, a prospective observational study is ongoing to follow up with patients from the FIRST-Dx study and assess the survival benefits of CGP prior to SOC. Additionally, limited drug access in Japan due to restrictions on off-label use poses a challenge, as patients cannot receive off-label drugs even if they have recommended treatments with rare driver gene alterations or high matching scores.

“To introduce precision oncology effectively in clinical practice, an extended option for patients with cancer to gain access to an investigational drug outside of clinical trials, such as a compassionate use program, might improve the accessibility of anticancer drugs in Japan,” the authors said.


Matsubara J, Mukai K, Kondo T, et al. First-line genomic profiling in previously untreated advanced solid tumors for identification of targeted therapy opportunities. JAMA Netw Open. 2023;6(7):e2323336. doi:10.1001/jamanetworkopen.2023.23336

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