Real-World Evidence for Liquid Biopsy to Identify Molecular Alterations

Web Exclusives — December 7, 2022

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.

Patients were admitted to the international department of Gustave Roussy with advanced solid cancers. Cell-free DNA was extracted from the patients’ (N = 47) 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 Eastern Cooperative Oncology Group 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.

Source: 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.

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