REDWOOD CITY, Calif. – March 21, 2017 — New findings from researchers at Massachusetts General Hospital Cancer Center and Harvard Medical School demonstrate the ability of the Guardant360® assay, the most-widely ordered comprehensive liquid biopsy, to overcome challenges that intra- and inter-tumor heterogeneity present to treating patients with advanced cancer.
The research, which was published this month in Cancer Discovery, described the effects of an investigational drug that inhibits the activity of FGFR2 mutations in cholangiocarcinoma. Researchers also examined the ability of Guardant360 to characterize new resistance alterations that arose in response to the treatment.
The results suggest that the inclusion of a comprehensive liquid biopsy may be the optimal method for identifying resistance alterations in patients with advanced cholangiocarcinoma, as it can provide a summary of the mutations occurring across the patient’s entire disease burden.
“As the sensitivity of circulating DNA sequencing increases, this may become the primary method through which the genomic evolution of tumors is evaluated,” an editorial published in the same March 2017 issue of Cancer Discovery noted. “The limitations imposed by the spatial boundaries of biopsies may needlessly limit our capacity to fully comprehend the complexity of heterogeneous tumors.”
While the prognosis for patients with advanced cholangiocarcinoma is poor, with median survival of less than one year, a new class of drugs is showing promise for treating the up to 20 percent of cholangiocarcinoma cancers that harbor FGFR2 fusions. In this phase 2 trial of BGJ398, an FGFR2 inhibitor, patients demonstrated a significantly improved objective response rate of 22% and a median time on treatment of 188 days.
As is the case with many targeted drugs, the cancer eventually developed resistance to the treatment, and the disease progressed. At the time of progression, researchers collected blood samples from a sub-group of trial subjects for Guardant360 testing and identified several novel resistance alterations, along with one well-known gatekeeper alteration, all in the FGFR2 gene.
Single lesion tissue biopsies performed at disease progression from the same patients contained only a fraction of the alterations detected by Guardant360, researchers reported. Additionally, in a rapid autopsy performed after one of the patients in the study died, twelve additional tissue biopsies from multiple metastatic lesions identified several more mutations missed in the original tissue biopsies but detected by Guardant360. Importantly, those resistance mutations were absent from lesions that had been shown, by CT scan, to be responding to the trial drug.
“These findings are further evidence of the potential of ctDNA to provide a more global summary of the genomic alterations present in advanced cancers. Here, a tissue biopsy failed to capture the full picture of tumor heterogeneity and missed important resistance alterations. This is significant in diseases where acquired resistance can inform treatment decisions, especially in cholangiocarcinoma, as next-generation FGFR2 inhibitors are already in clinical trials,” said Dr. Richard Lanman, Guardant Health’s Chief Medical Officer.
About Guardant Health
Guardant Health is focused on conquering cancer by using its breakthrough blood-based assays, vast data sets, and advanced analytics. Using both molecular and digital tools, Guardant Health is addressing challenges across the cancer care continuum. The company has raised more than $200 million from leading venture capital firms. Its first product, the Guardant360 assay, came to market in 2014, and is now the most widely ordered comprehensive liquid biopsy commercially available. In 2016, it announced Project LUNAR, an effort to apply Guardant Health’s technology platform to early detection, recurrence monitoring, and assessing minimal residual disease. Guardant Health and Guardant360 are registered trademarks of Guardant Health, Inc.