Precision medicine has advanced cancer treatment dramatically, and patients with metastatic colon and rectal cancer can achieve significant benefits when clinicians genotype tumors and use the data to guide therapy. Targeted therapies and immunotherapies have been shown to improve clinical outcomes. For example, anti-EGFR therapies are commonly used in treating metastatic colon cancer but are not efficacious in patients whose tumors harbor KRAS, NRAS,or BRAFV600Emutations. Professional guidelines continue to be updated as new therapies come to market such as the recent recommendation to test patients for NTRK fusions because they may benefit from treatment with tumor-agnostic NTRK inhibitors.
Many of the newer cancer drugs can only work if the patient is positive for certain mutations, and failure to test not only prevents the patient from being given the best therapy for their disease, but patients often do not respond to a therapy that was designed for a mutation they do not have. The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines recommend biomarker testing for all patients with metastatic colon cancer to screen for genomic alterations in KRAS, NRAS, BRAF, ERBB2 (HER2), NTRK and microsatellite instability (MSI) to help guide effective treatment decisions.
However, a recent study has shown that only 28% of colon cancer patients receive targeted treatments, and only 40% were tested for biomarker mutations, which is troubling news. These findings are consistent with biomarker testing rates in metastatic lung cancer, another cancer type ASCO and NCCN guidelines recommend biomarker testing for. This multi-center, retrospective study also found that certain subgroups of patients were less likely to be tested than others. Suboptimal genotyping occurred more often if the patient was male, older than 65, progressed from early stage disease, or treated in a community cancer center. Furthermore, only 28 percent of patients on anti-EGFR treatments received the necessary testing to determine eligibility.
This study also showed that using a comprehensive panel, as opposed to single-gene testing, could possibly result in a 50% increase in guideline-recommended testing rates. Clinicians face a difficult scenario with historic testing options, as tissue-based tests require surgery, are costly, and take weeks to turn results. A new methodology that uses a cell-free DNA testing – a methodology that relies on a blood-based testing rather than tissue testing – may help to improve these rates.
“For over a decade, medical guidelines have recommended multigene mutation testing for metastatic colon and rectal cancer patients to ensure patients receive the optimal treatment available. While the study shows that testing has improved slightly, the disappointing reality is that the majority of patients, including those receiving targeted treatments, are not being comprehensively tested,” said Stuart Goldberg, MD, a lead study investigator who served as chief scientific officer at COTA, Inc. for the Guardant360 project. “Personalized medicine holds great promise for achieving better outcomes, but we will not see the benefits until genomic testing is routinely adopted into clinical practice.”
Earlier in 2019, Guardant (a company that has created a liquid biopsy test for genetic mutations in cancer patients) showed in a study for lung cancer for their new product, Guardant360, could effectively test lung cancer patients for four mutations. The company is seeking to expand use of Guardant360 to other cancer types, including colorectal cancer. Clinical trials to compare this liquid biopsy method to traditional tissue biopsy are ongoing.
“Newly available therapies routinely help some people with metastatic colorectal cancer gain a year or two of life, but these novel treatments cannot be applied unless comprehensive genotyping is routinely performed,” said Richard Lanman, MD, Guardant Health Global Chief Medical Officer. “[It was] concerning that 28 percent of patients received targeted treatments without being tested, and for some we would have known in advance that the treatment was not going to work. At Guardant we are committed to helping reverse this trend by helping to educate oncologists and offering a non-invasive and comprehensive genomic testing solution that overcomes the limitations of tissue biopsies with our Guardant360 blood test.”
Hopefully, when these clinical trials are completed and liquid biopsy can become standard, genomic testing will be applied to all eligible patients, and improve the outcomes in treating metastatic disease through the promise of precision medicine.