Utility of Liquid Biopsy for Identification of Molecular Alterations in Solid Tumors

Identifying molecular alterations in patients with cancer is an important component of personalized therapy, which is supported by a growing body of evidence. Liquid biopsy, or cell-free DNA analysis, is a novel, noninvasive approach for identifying molecular alterations that has been confirmed in clinical trials, but real-world evidence has not yet been examined. This prospective, real-world study sought to examine liquid biopsy in international patients with cancer, specifically with the intent to offer personalized therapies. Results were shared at the 2022 ESMO congress.

A total of 47 patients were admitted to the international department of Gustave Roussy with advanced solid cancers, and cell-free DNA was extracted from the patients’ peripheral blood and sent for sequencing.

The median age of the patients was 60.5 years, and 53% of the patients were men. The primary site of cancer for these patients varied and included digestive (n = 20; 41%), lung (n = 9; 19%), sarcomas (n = 6; 13%), breast (n = 5; 11%), and other (n = 7; 16%). Treatment history also varied: 17 patients (36.2%) were treatment-naïve, 34 (73.3%) were previously treated with chemotherapy, and 16 (34%) were previously treated with immunotherapy. On the day of liquid biopsy, 43 patients (91.5%) had distant metastases. Patients with ECOG performance status scores 0-1 and ≥2 were split evenly with 24 patients (50%) in each group. The median number of previous lines of therapy was 1.

Only 2 patients had insufficient cell-free DNA to complete the liquid biopsy. For the remaining patients, the median number of molecular alterations was 5. In 7 patients, the tumor mutational burden was ≥10, suggesting that immunotherapy may be a treatment option. In addition, 10 molecular alterations with available options for treatment were identified in 9 patients: KRAS G12C (1 lung, 1 pancreatic), EGFR (1 lung), IDH1 (1 cholangiocarcinoma), BRAF (1 angiosarcoma, 1 colon), BRCA2 (1 pancreatic), PIK3CA (2 breast), and FGFR3 (1 bladder). Oncoprint genes were altered in ≥5% of patients.

The identification of the molecular alterations allowed for 15 patients (31.9%) to be offered an innovative approach to treatment. In addition, 16 patients (with 22 molecular alterations among them) were identified as potential participants in phase 1 or 2 clinical trials.

This study supports the role of liquid biopsy as a tool to identify molecular alterations with diagnostic and therapeutic implications.

Sources: Assi TS, Ibrahim T, Chahine C, et al. Liquid biopsy, a tool to detect genetic alterations with therapeutic impact in international patients: prospective data on 47 patients from Gustave Roussy. Ann Oncol. 2022;33(suppl 7):S580.

Assi TS, Ibrahim T, Chahine C, et al. Liquid biopsy, a tool to detect genetic alterations with therapeutic impact in international patients: prospective data on 47 patients from Gustave Roussy. European Society for Medical Oncology Congress 2022. Abstract 91P.