World GI 2017 Press Release: Liquid Biopsies: A Non-invasive Look at Treatment Response

BARCELONA, SPAIN, 30 June 2017 – A new study, to be presented at the ESMO 19th World Congress on Gastrointestinal Cancer, shows that so-called “liquid biopsies”, blood tests that detect circulating tumour DNA (ctDNA), may not only sound an early alert that a treatment’s effect is diminishing, but may also help explain why -sometimes offering clues about what to do next.

Why a cancer treatment is losing its effectiveness, is a question that preoccupies every patient and their doctor. But checking in on a drug’s tumor-fighting progress is not easy - usually involving invasive biopsies and expensive scans.

“We have shown that integrating regular liquid biopsies into our patients’ routine care is feasible and easily incorportated into clinical practice,” said study investigator Aparna Parikh, MD, from Massachusetts General Hospital Cancer Center, in Boston, Massachusetts.

“This technology can precisely help us understand each patient’s indvididual disease course and allows us to tailor care based on an understanding of their specific disease biology,” she said.

In fact, compared to standard tissue biopsies, which can be painful and difficult to obtain, her study showed that liquid biopsies actually provided more information less invasively.

The study involved nearly 40 patients with various forms of gastro-intestinal (GI) cancers, who had initially responded to therapy but then stopped.

Liquid biopsies were done when their disease began to progress and ctDNA in the blood was analysed for genetic mutations that might be making them resistant to treatment.

A total of 31 patients had at least one such mutation, and among them,14 had more than one.

Notably in about two thirds of patients who had traditional tissue biospies taken at the same time, the liquid biopsy picked up extra mutations that could not be seen in the tissue.

“Identifying what specific mutations are responsible for treatment resistance is very important in helping clinicians choosing what treatment path a patient should try next, whether it be another drug or perhaps radiation,” explained Parikh. 

While liquid biopsies are not yet widely used outside of the research setting, Parikh believes they are set to transform cancer treatment. “We have shown this approach is feasible across many different GI cancers,” she noted. “The next step is to study how best to use this new technology in daily practice. It’s important for clinicians to understand its utility as well as its limitations.” 

Commenting on the study, ESMO spokesperson Frederica Di Nicolantonio, MD, from the Candiolo Cancer Institute and University of Torino in Italy said, “this work elegantly reports that the use of clinical liquid biopsy panels can effectively identify multiple heterogeneous and co-occuring mechanisms of acquired drug resistance, all in a non-invasive manner. Clinicians should be able to better individualise patient care based on results from this technology.”

-END-

Notes to Editors

References

  1. Abstract O-001 – ‘Systematic liquid biopsy identifies novel and heterogeneous mechanisms of acquired resistance in gastrointestinal (GI) cancer patients’ will be presented by Dr Aparna Parikh during ‘Session X: Presentation of Selected Abstracts - Colorectal Cancer’ on Friday, 30 June, 08:40 to 09:45 (CEST) in Auditorium B.

Disclaimer

This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.

About the ESMO World Congress on Gastrointestinal Cancer

The ESMO World Congress on Gastrointestinal Cancer is the premier global event in the field, encompassing malignancies affecting every component of the gastrointestinal tract and aspects related to the care of patients with gastrointestinal cancer, including screening, diagnosis and the latest management options for common and uncommon tumours.

About the European Society for Medical Oncology (ESMO)

ESMO is the leading professional organisation for medical oncology. With more than 15,000 members representing oncology professionals from over 130 countries worldwide, ESMO is the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.

About Imedex

Imedex is an industry leader in providing accredited, independent continuing medical education to health care professionals. We develop high quality scientific programming that translates the latest research into clinically relevant information. The activities have exceptional organization and outstanding educational value, with a proven sustained impact on disease management. Our programs focus on improving patient care around the world. With over 50,000 e-learning experiences annually and more than 100,000 live meeting attendees, since 2001, Imedex truly educates the global healthcare community. At Imedex, education is the best medicine®. Visit www.imedex.com for more information

Abstract for O-001

Systematic liquid biopsy identifies novel and heterogeneous mechanisms of acquired resistance in gastrointestinal (GI) cancer patients

Parikh Aparna1, Goyal Lipika2, Hazar-Rethinam Mehlika1, Siravegna Giulia3, Blaszkowsky Lawrence1, Russo Mariangela4, Van Seventer Emily1, Nadres Brandon1, Shahzade Heather1, Clark Jeffrey1, Allen Jill1, Iafrate A. John1, Ryan David P.5, Murphy Janet2, Bardelli Alberto4, Zhu Andrew1, Hong Theodore1, Corcoran Ryan5
1Massachusetts General Hospital Cancer Center, Boston, Massachusetts, 2Massachusetts General Hospital, Boston, Massachusetts, 3University of Torino, Candiolo , Torino, 4University of Torino, Candiolo, Torino, 5Massachusetts General Hospital, Boston, MA

Introduction: Understanding mechanisms of acquired resistance to targeted therapy can guide strategies to improve clinical outcome. Circulating tumor DNA (ctDNA) provides a non-invasive means to identify concurrent heterogeneous resistance mechanisms emerging during therapy.

Methods: Since January 2015, 35 patients (pts) with molecularly-defined GI cancers (24 colorectal (CRC), 8 biliary, 3 gastroesophageal (GE)) achieving response or prolonged stable disease on targeted therapies had plasma collected at disease progression for next-generation sequencing of ctDNA. Molecular alterations identified were compared to ctDNA and/or tissue obtained pre-treatment to identify mechanisms of acquired resistance. When possible, post-progression tumor biopsies were also analyzed. Serial ctDNA specimens were evaluated to determine if the change in ctDNA levels can predict response to targeted therapy.

Results: In 35 pts, at least one molecular mechanism of resistance was identified in progression ctDNA in 28 pts (80%) with 15 (43%) exhibiting >1 resistance alteration (range 2-12, median 3). Overall, 72 total resistance alterations were identified. 14 pts had matched progression tumor biopsies, and resistance alterations were identified in 9 (61%), all of which were detected in matched ctDNA. In 64% of these pts, additional resistance mechanisms not detected in the matched tumor biopsy were identified in ctDNA. In 7 pts with multiple progression tumor biopsies available, distinct metastases showed different resistance alterations, all of which were detectable in ctDNA, but in 6 (86%) of these pts, ctDNA detected additional resistance alterations not found despite multiple tumor biopsies, reflecting extensive heterogeneity. Several critical and/or novel resistance alterations were identified across tumor types treated with diverse therapies. In 14 of 17 RAS wildtype CRC pts receiving EGFR antibodies, 28 total (13 distinct) resistance alterations affecting KRAS, EGFR extracellular domain, MEK1, MET, and ERBB2 were detected. In 3 of 5 BRAF mutant CRC pts receiving BRAF inhibitor combinations, 10 total (9 distinct) resistance alterations affecting MAPK genes (KRAS, NRAS, BRAF, MEK1, MEK2) were detected. In a MET-amplified GE pt receiving a MET inhibitor, 2 novel secondary mutations in the MET kinase domain were identified. In 5 FGFR2 fusion-positive biliary pts receiving an FGFR inhibitor, all patients developed novel secondary FGFR2 kinase mutations (13 total, 8 distinct), with 2 pts harboring 5 concurrent mutations, and one harboring 2. In serial ctDNA specimens, the decrease in ctDNA levels by 4 weeks correlated with response and therapeutic outcome.

Conclusion: Systematic ctDNA analysis at disease progression can effectively identify novel and heterogeneous mechanisms of acquired resistance in pts receiving targeted therapies for a range of molecularly-defined GI cancers. Compared to parallel tumor biopsies, ctDNA more effectively captured the heterogeneity of acquired resistance mechanisms, which may be important to guide subsequent therapy. Real-time monitoring of ctDNA levels may also represent a potential approach to predict response and resistance to therapy.  Further studies to optimize integration of ctDNA in clinical decision-making are warranted.