1225P - Combining ctDNA and tissue-based-genomic profiling in advanced cancer: A real-world evidence prospective study in non-Western patients treated at Gustave Roussy cancer campus

Background

Tissue-based genomic profiling (TBGP) is the gold standard to detect targetable pathogenic variants (PV) in advanced cancer patients (ACP). Circulating tumor (ct) DNA analysis could overcome the limitation of temporal and spatial heterogeneity. Nevertheless, some targetable PV detected in TBGP could be missed by ctDNA. Also, a few studies addressed the real-world evidence (RWE) of using ctDNA in non-western ACP. We aimed to evaluate the role of comprehensive genomic profiling (CGP) combining ctDNA and TBGP in international ACP treated at Gustave Roussy cancer campus.

Methods

This is a prospective study initiated on 01/10/2021. Peripheral blood was sent to Foundation One Liquid CDx for ctDNA analysis. TBGP was performed on DNA extracted from FFPE tissue using a specific panel for each tumor type. We used the oncokb online database to assess the level of actionability of PV.

Results

56 pts had paired analysis with 31 females, and a mean age of 59 years. The 4 most common primaries were colorectal cancer (14 pts), non-small cell lung cancer (8 pts), soft tissue sarcoma (8 pts) and breast cancer (7 pts). Success rates were 73.2% and 98.2% for TBGP and ctDNA respectively. Among the 14 pts with ctDNA success/TBGP failure, 1 had R1 (level 1 evidence for resistance), 3 L1 (level 1 evidence of actionability), 3 L4 and 45 nonactionable PV. Among the 41 pts with double success, 6 R1 and 5 L1 were detected by both techniques. Five R1 and 2 L1 were detected only in ctDNA, while 2 L1 were detected only by TBGP. Most PV detected only in ctDNA had no level of evidence (110/137).

Conclusions

Combining ctDNA and TBGP seems better than using only one technique. It should be noted that the high level of failure in FFPE-TBGP point out to the need of fresh tissue biopsies. More studies comparing the targetable PV in ACP from different countries are needed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.