Time is of the Essence

For patients diagnosed with late-stage cancer, the longer treatment is delayed, the poorer the clinical prognosis,1-4 yet capturing a comprehensive picture of the disease is essential for determining the most appropriate first-line treatment. This is underscored by the fact that some 50% percent of advanced cancer patients will not survive long enough to undergo second-line therapy.5 When oncologists have the benefit of comprehensive genomic profiling (CGP), they are able to make optimal treatment decisions.6 Unfortunately, not all advanced cancer patients who could benefit from targeted therapies are being tested. For example, 80% of patients with advanced non-small cell lung cancer7 and 60% of patients with late-stage colon cancer do not receive guideline-recommended CGP.8

The Race Against Time

Genomic testing with tissue requires significant clinical resources, patient risk, healthcare costs, and time. Oncologists often order single-gene testing, intuiting that testing for fewer genes will require less time. However, this approach takes weeks because the tests are run sequentially. Furthermore, even when a broad tissue panel is ordered, 33% to 79% of the time tissue depleted, rendering “quantity not sufficient” (QNS), either due to actual specimen size, tumor cellularity, or both.9-11 The entire tissue testing process is lengthy, delaying treatment as disease progresses.

In addition to the health and survival implications, studies show that the process of waiting, in and by itself, can greatly increase anxiety and depression and diminish health-related quality of life for oncology patients.12,13

To address the urgency of the clinical circumstances, oncologists are often compelled to begin uninformed treatment while awaiting results. Consequently, patients are put on immunotherapy, chemotherapy, or both, despite many clinical studies indicating that biomarker-positive patients who receive the appropriate targeted therapy have greater progression-free survival rates and higher overall response rates.14-20

Treat at the Speed of Cancer

A blood test is less invasive, safer, and less painful. Research indicates that patients have a better experience with liquid biopsy over surgical biopsy.21 Beyond improving the patient’s quality of life, liquid biopsies are also easier for oncology practices by eliminating a myriad of logistical challenges associated with tissue.

Guardant360 CDx,22,23 the first comprehensive liquid biopsy approved by the FDA, provides guideline-recommended genomic results in 7 days, to facilitate rapid clinical decision making. The assay uses proprietary next-generation sequencing technology to simultaneously detect mutations in a broad panel of clinically-relevant solid tumor genes. Real-time notifications are sent when results are ready, so that providers can quickly see the report with matched therapy or clinical trial insights.

Leading with liquid biopsy circumvents the unpredictable and lengthy process of tissue testing, providing a minimally-invasive, swift, accurate, and repeatable alternative that has been FDA-validated. Indeed, as precision medicine continues to advance the practice of oncology, Guardant360 CDx liquid biopsy is quickly becoming the new standard of care.

references

  1. Mohammed N, Kestin LL,Grills IS, et al. Rapid disease progression with delay in treatment of non–small cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;79(2):466-472.
  2. Hanna T, King WD, Thibodeau S, Jalink M, Paulin GA, et al. Mortality due to cancer treatment delay: systematic review and meta-analysis BMJ 2020; 371 :m4087
  3. Shen SMH, Hung YC, Kung, PT, Yang WH, Wang YH, Tsa WC. Factors involved in the delay of treatment initiation for cervical cancer patients, Medicine. 2016 August. Volume 95 – Issue 33 – p e4568
  4. Mohammed N, Kestin LL, Grills IS, Battu M, Fitch DL, Wong CY, Margolis JH, Chmielewski GW, Welsh RJ. Rapid disease progression with delay in treatment of non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011 Feb 1; 79(2):466-72. doi: 10.1016/j.ijrobp.2009.11.029. Epub 2010 May 13.
  5. Schwartzberg L, Korytowsky B, Penrod JR, et al. Real-world clinical impact of immune checkpoint inhibitors in patients with advanced/metastatic non–small cell lung cancer after platinum chemotherapy. Clinical Lung Cancer. 2019; 20(4): 287-296.
  6. Nesline MK, DePietro P, Dy GK, et al. Oncologist uptake of comprehensive genomic profile guided targeted therapy. Oncotarget. 2019 Jul 23; 10(45):4616-4629.
  7. Leighl NB, Page RD, Raymond, VM, et al. 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. Published Online First. 2019 April 15.
  8. Gutierrez et al. 2019 JCO Precision Onc.
  9. Denisov E, Gerashchenko T, Zavyalova M, Manskikh V, Choinzonov E, Nadezda C, Perelmuter V. Inter- and intratumor heterogeneity in hepatocellular carcinoma. 2016. 10.1007/978-3-319-34214-6_14.
  10. Wu J, Hu S, Zhang L, Xin J, Sun C, Wang L, Ding K, Wang B. Tumor circulome in the liquid biopsies for cancer diagnosis and prognosis. Theranostics. 2020 Mar 15; 10(10): 4544–4556.
  11. Shaw AT, Riely GJ, Bang Y-J, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019; 30(7):1121-1126.
  12. Rosenbaum EH, Rosenbaum IR. Hurry up and wait. Coping Magazine. n.d.
  13. Moseholm E, Rydahl-Hansen S, Overgaard D, et al. Health-related quality of life, anxiety and depression in the diagnostic phase of suspected cancer, and the influence of diagnosis. Health Qual Life Outcomes. 2016 May 20; 14:80.
  14. Ramalingam SS, Gray JE, Ohe Y, et al. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. Ann Oncol. 2019; 30(5): v851-v934.
  15. Garon EB, Hellmann MD, Costa EC, et al. Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001. J Clin Oncol. 2019; 37(28):2518-2527.
  16. Camidge DR, Dziadziuszko R, Peters S, et al. Updated efficacy and safety data and impact of the EML4-ALK susion variant on the efficacy of alectinib in untreated ALK-positive advanced non–small cell lung cancer in the global phase III ALEX Study. J Thorac Oncol. 2019; 14(7):1233-1243.
  17. Novartis. Efficacy of Tafinlar-Mekinist in metastatic non-small cell lung cancer with BRAF V600E. n.d. https://www.hcp.novartis.com/products/tafinlar-mekinist/metastatic-nsclc/efficacy/ Accessed online Jan. 10, 2020.
  18. Gadgeel SM, Garassino MC, Esteban E, et al. KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC. J Clin Oncol. 2019; 37(suppl; abstr 9013)
  19. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006; 14;355(24):2542-2550.
  20. Venkatesan S, Charles Swanton C. Tumor Evolutionary Principles: How Intratumor Heterogeneity Influences Cancer Treatment and Outcome. American Society of Clinical Oncology Educational Book 2016; 36, e141-e149.
  21. Lee MJ, Hueniken K, Kuehne N, et al. Cancer Patient-Reported Preferences and Knowledge for Liquid Biopsies and Blood Biomarkers at a Comprehensive Cancer Center. Cancer Manag Res. 2020 Feb 13; 12:1163-1173.
  22. U.S. Food & Drug Administration. FDA approves first liquid biopsy next-generation sequencing companion diagnostic test. Fda.gov. Aug. 7, 2020. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-first-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test.
  23. Guardant. Backgrounder: Guardant360® CDx now FDA approved. n.d.

Targeted cancer therapies are prolonging patient survival times and improving quality of life,1 outcomes which are facilitated by tumor mutation profiling.2 Because cancer genomes are complex, comprehensive genomic profiling (CGP) offers the greatest insight into optimal treatment. In a 2020 study published in Cancers (Basel)3, “CGP identified at least one potentially clinically actionable genomic alteration in 95% of all patients tested”.

Regardless of the percent, it is critical that patients are both tested and are then treated based on CGP results. The easiest, most expedient way to ensure patients receive tumor genotyping is with plasma-based testing. Because precision medicine continues to advance oncology, liquid biopsy is quickly becoming a new standard of care.4

Guardant360 CDx, the first comprehensive liquid biopsy approved by the FDA,5 provides guideline-recommended genomic results in 7 days. The assay uses proprietary next-generation sequencing technology to simultaneously detect mutations in a broad panel of clinically-relevant solid tumor genes.

Liquid Biopsy: Better Insight, Better Care, Better Outcomes

Leading with liquid biopsy for comprehensive genomic profiling accelerates decision making and finds more patients altogether.

20% more patients with biomarkers detected using Guardant360 first

Source: Leighl et.al. Clin Cancer Research 2019

In the NILE Study, 282 patients with untreated nonsquamous NSCLC underwent SOC tissue genotyping and provided a pre-treatment blood sample for analysis of cell-free DNA (cfDNA). Compared with tissue genotyping, a higher percentage of liquid biopsies identified one of 8 key guideline-recommended biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, METex14, and ERBB2) (21.3% vs 27.3%; P < .0001).7

When cfDNA was used in addition to tissue, the detection of guideline-recommended biomarkers improved by 48%, rising from 60 to 89 patients, including those with negative tissue testing results (7), those not tested (16), and those whose samples were insufficient for tissue-based testing (6).7

FDA-approved Guardant360 CDx is the sole test to utilize the proprietary digital sequencing and ctDNA capture technology that facilitates high sensitivity, specificity, and substantially faster turnaround time than tissue alone.5

Comprehensive Liquid Biopsy as the Standard of Care

The ability to identify tumor mutations in such a minimally-invasive, swift, accurate, cost-effective, and repeatable way has a significantly favorable impact on both patients and providers. Adopting liquid biopsy as a standard of care is highly appealing to oncologists for all the rational reasons—ease of use, lower cost, and rapid results—but perhaps most convincing for healthcare providers is the superiority in detection.6 Finding more patients with oncogenic drivers ultimately leads to improved patient care and more favorable outcomes.8-10, 11-13

references

  1. Yuan, M, Huang, LL, Chen, JH, et al. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Sig Transduct Target Ther. 2019; 4, 61.
  2. Nalley C. Genomic profiling Identifies patients most likely to respond to immunotherapy. Oncology Times. 2017; 39(20):29,31.
  3. Singh AP, Shum E, Rajdev L, et al. Impact and diagnostic gaps of comprehensive genomic profiling in real-world clinical practice. Cancers (Basel). 2020 May 4; 12(5):1156.
  4. Panabieres C. The future of liquid biopsy. Nature. 2020; 579,S9
  5. U.S. Food & Drug Administration. FDA approves first liquid biopsy next-generation sequencing companion diagnostic test. Fda.gov. 2020 Aug 7; Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-first-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test.
  6. Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non–small cell lung cancer. JAMA Oncol. 2019; 5(2):173-180.
  7. Leighl NB, Page RD, Raymond VM, et al. 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; 25(15)4691-4700.
  8. Shaw AT, Riely GJ, Bang Y-J, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann. Oncol. 2019; 30(7):1121-1126.
  9. Ramalingam SS, Gray JE, Ohe Y, et al. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. Ann. Oncol. 2019; 30(5):v851-v934.
  10. Garon EB, Hellmann MD, Costa EC, et al. Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001. J Clin Oncol. 2019; 37(28):2518-2527.
  11. Novartis. Efficacy of Tafinlar-Mekinist in metastatic non-small cell lung cancer with BRAF V600E. n.d. https://www.hcp.novartis.com/products/tafinlar-mekinist/metastatic-nsclc/efficacy/ Accessed online Jan. 10, 2020.
  12. Gadgeel SM, Garassino MC, Esteban E, et al. KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC. J Clin Oncol. 2019; 37(suppl; abstr 9013).
  13. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006; 14;355(24):2542-2550.