710P - A retrospective study on the safety and adequacy of fresh biopsies for next generation sequencing in early-phase clinical trials

Background

Early-phase clinical trials are a unique opportunity for patients with cancer to benefit from innovative treatments. These trials usually demand newly-collected tumor tissue for research purpose, requiring patients to undergo new biopsies. Some trials require a prescreening by next-generation sequencing (NGS), but the analysis can be challenged by both the quality and the quantity of the samples. Biopsies may have procedural complications with negative impact on patients.

Methods

We retrospectively reviewed the records of patients referred to the Early Drug Development (EDD) Unit of European Institute of Oncology, who performed fresh biopsies for research purpose. We aimed at assessing safety of the biopsies and the adequacy of the tumor tissue for NGS testing.

Results

A total of 731 patients were referred to the EDD Unit from January 2014 to December 2022. Median age was 56 years (range 20 – 83) and 79% of patients were female. The most common tumor type was breast cancer (40%), followed by lung adenocarcinoma (6.2%), cholangiocarcinoma (5.8%), and carcinoma of unknown primary (5.8%). Three hundred fifty-five patients (48.6%) underwent a new biopsy at trial entry. Liver (148, 41.7%), lymph nodes (64, 18%), skin (47, 13.2%) and breast (7.3%) were the most frequent sites for biopsy. The median time from trial’s informed consent to biopsy was 3 days (range 0 – 83). The tumor tissue was commonly adequate for histological diagnosis (98%); NGS testing was successful in 122 (88.4%) of the 138 cases in which the trial required NGS testing. Nine out of the 16 unsuccessful NGS were performed on liver tissue. Eleven patients (3.1%) had procedural complications from the biopsy (5 pain, 3 minor bleeding, 2 pneumothoraxes, 1 bradycardia), but none required hospitalization nor led to sequelae. The only treatments administered were painkillers.

Conclusions

Approximately half of the patients referred to our EDD Unit performed a fresh biopsy. The procedure was generally safe, with only a minority of patients (3%) having non-serious complications. About 10% of NGS failed due to poor sample quality or quantity, highlighting the importance to implement specific information and Standard Operating Procedure for samples intended for NGS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Edoardo Crimini.

Funding

Has not received any funding.

Disclosure

D. Trapani: Other, EMA Healthcare Professional Working Party (HCPWP), member: European Medicines Agency (EMA); Other, EML Cancer Medicines Working Group (CMWG), member: World Health Organization (WHO); Other, Strategic Advisory Group of Experts on In Vitro Diagnostics (SAGE IVD), chair: World Health Organization (WHO). C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli-Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. All other authors have declared no conflicts of interest.