1659P - The use of liquid biopsy in patients with advanced pancreatic cancer (PDAC) to guide enrollment in phase I clinical trials

Background

Therapeutic possibilities in PDAC remain poor and access to tumor tissue for molecular profiling is still a challenge. The era of circulating tumor DNA (ctDNA) or liquid biopsy facilitated molecular screening and treatment orientation in selected patients (pts).

Methods

Data from PDAC pts who underwent liquid biopsy at the Drug Development Department (DITEP) at Gustave Roussy were collected. The primary objective was to assess the ability of liquid biopsy to find molecular alterations (MA), orient and include pts in early phase clinical trials. We evaluated the progression-free survival (PFS) on matched therapy (PFS2) compared to PFS on prior therapy (PFS1). Treatment efficacy was considered by focusing on the percentage of patients with a PFS2 that was 1.5 times greater than the PFS1, based on a standard calculation (PFS2/PFS1), and a modified formula (mPFSr) with mPFSr = postPFS/prePFS with postPFS = PFS2 if PFS2 < 6 months and postPFS = 24 months if PFS2 > 6 months; prePFS = PFS1 if PFS1 > 2 months and prePFS = 2 months if PFS1 < 2 months.

Results

Between January 2020 to November 2022, a total of 31 pts were included in the study. The main characteristics were as follow: median age of 62 years (32-81), median number of previous lines of treatment of 2 (0-4) and median ECOG Performance Status of 0 (0-2). Finally, 30 patients had a liquid biopsy at progression on their last treatment line. Targetable MA (FGFR, KRAS…) were found in 8 pts (27%), and 5 patients (17%) received a matched targeted therapy in an early phase clinical trial. FGFR alterations were the most frequent and 3 patients (60%) received FGFR inhibitors. From the 5 patients matched and treated, one patient (20%) had a PFS2/PFS1 ratio > 1.5 and three pts (60%) had an mPFSr > 1.5. With a median follow-up time of 12.3 months (9.2-NR), the overall response rate was 20%, the overall control rate was 100% and the median overall survival was not reached (8.5-NR months).

Conclusions

These results suggest that molecular profiling-matched therapy assessed by liquid biopsy could improve the therapeutic field in pancreatic cancer. However, only a small proportion of patients are matched and treated. Randomised trials are needed to confirm the value of this treatment method in pancreatic cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dr. S. Ponce Aix (DITEP, Gustave Roussy, Villejuif).

Funding

Has not received any funding.

Disclosure

A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, EISAI; Financial Interests, Personal, Advisory Board: Basilea, Tahio, Relay Therapeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345: AbbVie; Non-Financial Interests, Principal Investigator, CO42216; WP42627; CO40939: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seattle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Tahio; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim.