Personalized therapy in solid tumors: results of a retrospective multicentre study of the clinical applicability of the FoundationOne® Medicine Test
Authors: Stepanova M. L. , Kuznetsovа O. A. , Shilo P. S. , Moiseenko F. V. , Abduloeva N. Kh. , Artemyeva E. V. , Zhabina A. S. , Kramchaninov M. M. , Volkov N. M. , Pokataev I. A. , Rumyantsev A. A. , Plaksa I. L. , Gairyan M. A. , Isaev A. A. , Ivanov M. V. , Sadykova Yu. F. , Mileiko V. A. , Shamrikova V. V. , Ledin E. V. , Tryakin A. A. , Fedyanin M. Yu. 
Published: September 2022

Background. The use of targeted sequencing panels makes it possible to optimize and personalize the treatment strategy for cancer patients. Given the lack of a clear «portrait of the patient», the role of large panels (200 or more genes) in the treatment of a patient has not yet been determined.

Aim. Assessment of the relationship between the results of targeted sequencing of tumor tissue or ctDNA and the treatment carried out after obtaining these data in patients with various solid tumors.

Materials and methods. We retrospectively evaluated the NGS results and the treatments, provided to the 184 patients after NGS testing between 06.2016 and 06.2021. For analysis, one of two methods is used: a histological sample or the patient’s blood plasma. Evaluation of the results and determination of treatment tactics were carried out within the framework of a multidisciplinary commission. The frequency of detection of molecular disorders, the number of mutations in each sample, and the frequency of detection of targets for targeted therapy were assessed.

Results. Molecular disorders were detected in 88.5 % (n = 163). The average number of mutations in one sample was 6. The maximum was detected in colorectal cancer patients; their average value was 8. The minimum was determined in non-small cell lung cancer and ovarian cancer patients, the average number of mutations was 3 in each localization. The average time from the moment the material was received by the laboratory to the generation of the report was 11 days. Targeted targets were identified in 25 (13.6 %) patients and therapy was started. Therapy with tyrosine kinase inhibitors of the first – third generations were performed in 12 (48 %) patients, PARP inhibitors – in 3 (24 %), BRAF and MEK inhibitors – in 2 (8 %), anti-HER2 therapy – in 1 (4 %). Targeted therapy within international clinical trials was initiated in 4 (16 %) patients. Immunotherapy was recommended in 3 (12 %) patients. In multivariate analysis, the chance of prescribing therapy based on the results of FM1 analysis was influenced by: mRAS (odds ratio 0.08; 95 % confidence interval 0.01–0.65; p = 0.018) and mEGFR (odds ratio 4.8; 95 % confidence interval 1.4–16.3; p = 0.012).

Conclusion. The effectiveness of the FM1 test in real clinical practice in the Russian Federation corresponds to international data. In the presence of a mutation in the RAS genes, an additional FM1 test determines a low chance of detecting clinically significant disorders for which personalized treatment can be prescribed. The high frequency of prescription of therapy based on the results of blood plasma tests is due to the cohort of patients with non-small cell lung cancer and the detection of a mutation in the EGFR gene.