As FoundationOne®Liquid CDx marks its first anniversary as an FDA-approved liquid biopsy option for cancer patients, I’d like to look back over the past year and explore the progress we’ve made. In just 12 months, we have reached important milestones that have helped to define this test’s clinical utility, while also establishing the need for liquid biopsy comprehensive genomic profiling (CGP) across the wider precision medicine landscape.
August 26, 2020 marked the first FDA approval of a liquid biopsy CGP test with multi-cancer companion diagnostic (CDx) indications, and it also marked an important step for precision medicine. The approval was the culmination of over a decade of research and was a true testament to the deep genomic expertise and collective work of my colleagues to both build the test and navigate the regulatory pathway to bring it to patients.
Our comprehensive pan-tumor liquid biopsy test analyzes over 300 cancer-related genes, and the initial approval was granted with four CDx indications for targeted therapies to treat non-small cell lung cancer (NSCLC) and metastatic castration-resistant prostate cancer (mCRPC).
It was of pivotal importance to us that physicians would be able to use the test as quickly as possible following FDA approval in order to inform treatment decision making for their patients. Because of that centralized focus, FoundationOne Liquid CDx was launched in the U.S. only a few days after the FDA approval, with pan-tumor Centers for Medicare & Medicaid Services (CMS) coverage from day one.
Building evidence to secure trust and accelerate use
Gaining clinician trust in liquid biopsy is fundamental to its wider uptake and use in the community. A core focus for Foundation Medicine continues to be the generation and publication of original research that builds on the wealth of existing evidence, as well as our work to communicate that research and support education within the clinical community.
Clinical validity of liquid biopsy in >3000 patients with advanced prostate cancer (February 2020)
In February 2020, at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), we presented results from a study of more than 3,000 patients with mCRPC, designed to evaluate the landscape of genomic alterations identified by liquid biopsy as well as assessing concordance of liquid and tissue biopsy in over 800 of those patients.
The study demonstrated high concordance between targetable alterations identified using circulating tumor DNA (ctDNA) and tissue-based CGP in patients with mCRPC, detecting 93% of BRCA1/2 mutations that were identified in tissue-based testing. It also found that, in many patients, liquid biopsy detected more acquired resistance alterations than tissue biopsy.
In addition to the data presentation at ASCO GU, the full study, “Genomic analysis of circulating tumor DNA (ctDNA) in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms,” was published online in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Liquid biopsy’s potential for pan-tumor impact (June 2021)
In the early days of liquid biopsy’s use in cancer care, it was most frequently used by oncologists in treatment planning for patients with lung cancer. This year’s ASCO meeting was a showcase for the breadth of studies being undertaken that demonstrate the utility and potential of our blood-based CGP across a multitude of tumor types, expanding beyond lung into breast, prostate, ovarian and rare cancers.
For example, in a real-world clinical outcomes study that looked at the prevalence of PIK3CA mutations (PIK3CAm) in breast cancer patients, we were able to prove that CGP detects a broad spectrum of PIK3CA mutations and that liquid biopsy CGP detected PIK3CA mutations at a similar rate to tissue biopsy. This research reinforces the clinical utility in breast cancer of both testing types depending on the patient’s unique situation.
Also at ASCO, we reported on the first clinical data with blood tumor mutational burden (bTMB) from FoundationOne Liquid CDx, showing elevated bTMB in many of the same cancer types with elevated tissue TMB. Importantly, in plasma samples with higher tumor content their bTMB aligns more clearly with tissue TMB, suggesting that ctDNA shed is a variable in the detection of elevated bTMB. Ongoing clinical studies are looking at the actionability of bTMB for predicting immunotherapy benefit.
The importance of Guideline inclusion in shifting standards of care
Another important area of focus in our efforts to remove barriers to patient access to precision medicine is inclusion of blood-based CGP within national and international guidelines. These steps are imperative to cementing clinician trust and accelerating uptake. Generating the evidence needed to enable this to happen as swiftly as possible is a key driver for our data strategy and we have made significant progress in recent months.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) (February 2021)
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer strongly advocates a metastatic biopsy for histologic and molecular evaluation. When this is not possible, plasma ctDNA (circulating tumor DNA) assay is an option, preferably at time of biochemical PSA (prostate-specific antigen) or radiographic progression in order to maximize yield.
IASLC consensus statement on liquid biopsy use in NSCLC (July 2021)
The recent consensus statement from the International Association for the Study of Lung Cancer (IASLC) on the use of liquid biopsy in advanced NSCLC is an important step forward and should help to encourage and inform optimal use of liquid biopsy testing in lung cancer, and hopefully other disease areas to follow. The statement recognizes that tissue- and blood-based testing need to be use synergistically depending on the individual patient case. We’re working with professional groups across oncology to understand the perspectives of treating physicians and pathologists focused on other tumor types to support the inclusion of FoundationOne Liquid CDx in relevant guidelines.
Expanding the clinical utility of FoundationOne Liquid across disease types and globally across geographies
Building on the companion diagnostic indications in place at launch in August 2020, we have secured FDA approval for additional companion diagnostic indications in the U.S., and have received approval and launched the test in countries outside of the U.S.
Five additional companion diagnostic indications (October & November 2020, July 2021)
Fall of 2020 brought the FDA approval of FoundationOne Liquid CDx as a companion diagnostic for four additional therapies, including new indications for patients with mCRPC and anaplastic lymphoma kinase (ALK)-positive NSCLC—which is notoriously challenging to detect in ctDNA—as well as approvals that extended the test’s clinical utility into ovarian and breast cancers. And earlier this summer, we received our ninth CDx approval for FoundationOne Liquid CDx, this time for patients with metastatic NSCLC with MET exon 14 skipping. These subsequent approvals over the last 12 months reinforce our commitment to making our tests as actionable as possible for patients facing cancers of all types.
Regulatory approval and launch in Japan (March and August 2021)
Taking the benefits of CGP globally to all patients with cancer has long been our mission. It seems fitting that as we celebrate the anniversary of the launch of the test here in the U.S., the option of liquid biopsy CGP is also becoming a reality for patients internationally. The recent approval and launch of FoundationOne Liquid CDx Cancer Genomic Profile in Japan demonstrates important progress in bringing CGP to more patients outside of the U.S. and is a result of over 3 years of collaborative work with our biopharma partner, Chugai; work that will continue as we evolve our portfolio in response to the needs of Japanese patients and the wider health system.
What does the future hold for liquid biopsy CGP?
One area of huge potential in the near future is disease monitoring. The recent launch of FoundationOne®Tracker, our personalized ctDNA monitoring assay, for research use is a significant step forward and is a result of the combined knowledge of our team of scientists with the deep expertise of our partner Natera, in the science of ctDNA testing.
But for us, the future is not just about new applications for our portfolio. We continually strive for improvement and innovation – in the sensitivity of our tests, the research and insights we generate, the services we provide to clinicians and the power of our partnerships. This will ensure that we continue to meet the rapidly changing needs of clinicians and patients in this increasingly complex field of medicine.
So, in conclusion, what difference has the last 12 months made for patients? The achievements and progress we’ve seen over the past year means that now, for a significant population of patients across multiple solid tumor types, in multiple countries around the world, high-quality liquid biopsy is a reality that is within reach. This is truly a huge achievement for everyone involved, and for us at Foundation Medicine, it is another step forward in our mission to transform cancer care through precision medicine.
1) FoundationOne Liquid CDx approval announcement: https://www.foundationmedicine.com/press-releases/445c1f9e-6cbb-488b-84ad-5f133612b721
2) Tukachinsky H, et al. Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms. JCO Volume 39, Issue 6_suppl.
3) Tukachinsky H, et al. Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms. Clin Cancer Res 2021;27:3094-105
4) Rugo HS, et al. Real-world (rw) clinical outcomes on alpelisib (ALP) in patients (pts) with breast cancer (BC) and PIK3CA mutations (PIK3CAm). J Clin Oncol 39, 2021 (suppl 15; abstr 1068)
5) Yoshino T, et al. Genomic immunotherapy (IO) biomarkers detected on comprehensive genomic profiling (CGP) of tissue and circulating tumor DNA (ctDNA). JCO Volume 39, Issue 15_suppl.
6) Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V2.2021. National Comprehensive. Cancer Network, Inc. 2021. All rights reserved. Accessed August 18, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
7) Rolfo C, et al. Liquid Biopsy for Advanced Non-Small Cell Lung Cancer: A Consensus Statement from The International Association for the Study of Lung Cancer (IASLC). J Thorac. Oncol. 2021 Jul 8;S1556-0864(21)02284-X
8) Evidence Dossier, FoundationOne Liquid CDx. https://info.foundationmedicine.com/hubfs/FMI%20Dossiers/FoundationOneLiquidCDx_Evidence_Dossier.pdf
9) Alexander B. Making Comprehensive Genomic Profiling Indispensable at a Global Level: Progress, Perspectives and What’s Next: Foundation Forward. https://www.foundationmedicine.com/blog/making-comprehensive-genomic-profiling-indispensable-at-a-global-level
10) Foundation Medicine Launches FoundationOne®Tracker ctDNA Monitoring Assay for Research Use in Partnership with Natera. Press release, Foundation Medicine. https://www.foundationmedicine.com/press-releases/bdeffc0c-20e6-467b-8042-8979b1ed4c49