What if a simple blood draw taken during a routine visit to the doctor for a check-up or a flu shot could allow us to identify specific cancers at an early stage, when they are the most treatable? What if blood tests could help the cancer care team improve patient care at every step of the patient’s journey—from detection to treatment selection to response and recurrence monitoring?
We’re currently living through a revolution in the detection and treatment of cancer by way of precision medicine. Innovative biomarker technology and targeted therapeutics are transforming the way we identify and manage cancers, enabling more people with cancer to live longer and healthier lives. Since the 1960s, the five-year survival rate of cancer patients has increased from 35% to 65%.[1]
And that’s only the beginning. In recent years, we’ve seen a dramatic increase in the number of targeted therapies approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Drugs targeting specific genomic alterations of a patient’s cancer, or biomarkers, can be more effective than one-size-fits-all chemotherapy or immunotherapy, doubling or even tripling patient life expectancy in many instances, while reducing the debilitating side effects.
This revolution in personalized medicine has been fueled in large part by the relatively recent introduction of comprehensive genomic profiling (CGP) for advanced-stage solid cancers. Analyzing the genomic makeup of tumor cells and the evolution of resistance mechanisms through the use of tissue biopsies has enabled us to discover actionable information that can be used to inform treatment selection.
However, the use of tissue biopsies for genomic profiling has limitations. For some cancers at diagnosis —notably, advanced lung cancer—safely accessing a sufficient volume of tissue to perform a biopsy can be a challenge. To reassess the cancer genomic profile through tissue if there is cancer progression is even more challenging. Even when accessing tissue is not an issue, a tissue biopsy can be complex and carry moderate or greater risk of complications. These factors help explain why, for example, fewer than 20% of patients with advanced lung cancer receive genomic profiling at initial diagnosis. In addition, the time required to turn around CGP results from the tissue biopsy—often up to three weeks—delays the oncologist’s ability to initiate therapy and can create anxiety for patients while they wait to find out the results.
Addressing this significant unmet medical need is where liquid biopsy comes in.
Blood-based tests can complement tissue biopsies when tissue is accessible by providing additional information, and typically faster (e.g., complete genomic profile results in seven days). By looking at the unique dimensions of cancer found in blood—including genomic alterations, methylation, and fragmentomics—we can uncover insights that can help patients across all stages of cancer. Today, blood-based, next-generation sequencing tests are helping us realize the full potential of precision oncology by providing patients and their doctors with critical insights that can inform decisions in disease detection (screening), treatment selection and recurrence monitoring.
Informing treatment selection, response and recurrence monitoring
In advanced cancer, the use of liquid biopsies for comprehensive genomic profiling has helped accelerate both the development and adoption of precision medicines, or targeted therapies, which have made a radical difference in improving outcomes for patients battling advanced cancer.
In 2020, the FDA approved the first liquid biopsy for comprehensive genomic profiling across all solid cancers and as a companion diagnostic test for a non-small cell lung cancer (NSCLC) therapy. Since then, the number of FDA-approved targeted therapies and associated companion diagnostic blood tests has continued to grow, enabling oncologists to complete guideline-recommended comprehensive genomic testing through a simple blood draw to help match their patients to these therapies quickly. Liquid biopsies are also being used to monitor patient response to therapy, helping doctors refine treatment even further.
For example, a study published in Nature demonstrated that a liquid biopsy test can help guide treatment decisions for patients with HER2-driven metastatic colorectal cancer (mCRC). The phase II study demonstrated that the test could select patients for HER2-directed therapy, identify which patients are responding to treatment, and identify genetic alterations that predict resistance.
In early-stage cancer, liquid biopsy tests can be used to detect minimal residual disease (MRD) after surgery, to give doctors a better understanding of which patients are at high risk for recurrence. They can detect MRD through circulating tumor DNA (ctDNA) in a patient’s blood, looking at both genomic alterations and methylation. By interrogating these crucial signals in the blood, liquid biopsy can identify patients with residual disease who may benefit most from adjuvant therapy and detect cancer recurrence.
Overcoming barriers to cancer screening compliance
While liquid biopsy tests have opened new opportunities in early-stage and advanced cancer care, their greatest potential to impact patient outcomes may be as a screening tool.
Once the stuff of dreams, it is now possible for a blood test to detect very early signs of cancer in average-risk adults without symptoms by interrogating genomic alterations, methylation, and fragmentomic signals. Of course, good screening tests for several common cancers already exist. The challenge is that many patients find those screening tests unpleasant, time-consuming or difficult to complete. For example, an estimated one in three people in the U.S. today are not being screened for colorectal cancer in line with current guidelines, in part because of the discomfort, disgust or inconvenience associated with colonoscopy and stool-based tests. Liquid biopsies can overcome these barriers and increase screening rates by offering individuals an accurate test that is easy to complete via a simple blood draw at any patient visit. Increasing screening rates for common, treatable cancers could save countless lives each year.
As precision oncology has evolved, its potential to improve patient outcomes by identifying and targeting specific biomarkers, in particular through comprehensive genomic profiling, has become abundantly clear. The introduction and growing sophistication of liquid biopsy over the past decade has expanded that potential significantly. Today, analyzing the unique dimensions of cancer found in blood is unlocking new insights that allow healthcare professionals to make more informed decisions for their patients across the entire continuum of cancer care.
Reference
[1] Cancer Facts & Figures 2019. American Cancer Society (ACS). Online. Last accessed on February 15, 2023
[2] Leighl NB, Page RD, Raymond VM, Daniel DB, Divers SG, Reckamp KL, Villalona-Calero MA, Dix D, Odegaard JI, Lanman RB, Papadimitrakopoulou VA. Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non-small Cell Lung Cancer. Clin Cancer Res. 2019 Aug 1;25(15):4691-4700. doi: 10.1158/1078-0432.CCR-19-0624. Epub 2019 Apr 15. PMID: 30988079.
[3] Nakamura Y, Okamoto W, Kato T, Esaki T, Kato K, Komatsu Y, Yuki S, Masuishi T, Nishina T, Ebi H, Sawada K, Taniguchi H, Fuse N, Nomura S, Fukui M, Matsuda S, Sakamoto Y, Uchigata H, Kitajima K, Kuramoto N, Asakawa T, Olsen S, Odegaard JI, Sato A, Fujii S, Ohtsu A, Yoshino T. Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial. Nat Med. 2021 Nov;27(11):1899-1903. doi: 10.1038/s41591-021-01553-w. Epub 2021 Nov 11. PMID: 34764486; PMCID: PMC8604726.
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