New Way to Personalize Treatment With PD-1 Inhibitors

Tissue biopsies have been the gold standard for gathering genetic information on tumors: a small tissue sample is taken and analyzed for genetic variations or mutations that are specific to the tumor. However, there may be a time lag to interpretation of results, and tissue biopsies can be difficult or even dangerous to conduct. Further, tissue biopsies collect only a snapshot from a single location in a tumor and may fail to capture the full genetic “picture”. We know the genetic profile can vary from one location to another within a single tumor (intra-tumoral heterogeneity) and/or from one tumor site to another in the patient (intra-patient heterogeneity).

Having a detailed view of tumor genomics is particularly important when determining response to therapy and potentially evaluating treatment options, and at the Late-Breaking Clinical Research session at this year’s Annual American Association for Cancer Research (AACR) meeting, BeiGene colleagues are presenting data on a less invasive way to evaluate tumor genomics. We conducted a retrospective analysis evaluating circulating tumor DNA (ctDNA) in blood samples from two large Phase 3 clinical trials with our PD-1 inhibitor tislelizumab.

Circulating tumor DNA, or ctDNA, offers an alternative method to identifying tumor-specific biomarkers that can complement and potentially replace some tissue biopsies. ctDNA consists of fragments of DNA that are released into the patient’s bloodstream by tumor cells. It is gathered by taking a blood sample from the patient in a minimally invasive procedure – sometimes referred to as a “liquid biopsy” – and analyzing the DNA fragments in the blood sample for tumor-specific biomarkers.

Because ctDNA may come from any tumors present, ctDNA casts a wide net for tumor biomarkers, capturing intra-tumoral and/or intra-patient heterogeneities a tissue biopsy might miss and potentially providing a fuller, more representative genetic profile of a patient’s cancer. This detailed understanding can aid in making informed decisions about optimized treatment regimens based on the mutation profile in an individual patient.

In addition to specific genetic information, total levels of ctDNA in the blood sample can provide a measure of the total tumor burden in the patient. Assessing any changes in total ctDNA at periodic intervals could provide an indication of response to treatment sooner than might be captured through scans or biopsies. At BeiGene we are exploring how novel measures such as ctDNA might help us make early and smart decisions as we look to bring innovative medicines to more patients with cancer across the world.

You can find our late-breaking abstract (LB289) within the AACR program planner here.