Progression Free Survival After Liquid Biopsy Similar to Rates After Tissue

December 6th, 2021

Rebecca Nagy, Vice President Medical Affairs, Guardant Health, Professor Clinical Internal Medicine, Licensed Genetic Counselor

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As liquid biopsy continues to gain recognition as an invaluable clinical tool in the treatment of all metastatic solid tumors, this blood-first approach is being recommended more and more often in treatment guidelines, including those from the International Association for the Study of Lung Cancer (IASLC).1

The most dramatic advances are seen in the treatment of non-small cell lung cancer (NSCLC). This is in large part due to the complex genomic characteristics of the disease and the steadily increasing number of actionable mutations, as new drugs prompt clinical trials and gain Food and Drug Administration approval. With liquid biopsy, not only are these actionable mutations identified more often, less invasively, and more rapidly, but patient outcomes are also very promising.

A 2021 prospective study (SLLIP)2 reported in JCO Precision Oncology adds to the growing body of evidentiary support for liquid biopsy, as demonstrated elsewhere.3-5 Results of the SLLIP study confirm that applying a blood-first approach for the detection of genomic biomarkers can identify a greater number of actionable biomarkers than a tissue-first approach. The most significant results to come out of the SLLIP study and reinforce previous research are those showing remarkably similar objective response rates and progression free survival (PFS) when compared with those reported after targeted treatment that was guided by tissue-based Comprehensive Genomic Profiling.

The non-inferiority study compared Comprehensive Genomic Profiling using Guardant360® liquid biopsy versus tissue genotyping to make first-line treatment determinations in 186 patients with advanced NSCLC. The study met its endpoint and revealed that cell-free DNA (cfDNA) identified actionable mutations in 46 patients who had liquid biopsy versus 48 patients who had a tissue biopsy (P < 0.05). Those advanced NSCLC subjects were treated with matching targeted therapies, based on either cfDNA or tissue results. As a result, PFS for the 41 patients with blinded RECIST assessment receiving targeted therapy showed a median PFS of 8.6 months (95% CI, 7.6 to 11.6). PFS for the cfDNA positive and tissue positive cohorts are shown in the figure below.2

Progression-free survival in the tissue positive cohort, compared with the cfDNA positive cohort. cfDNA, cell-free circulating tumor DNA.

FIG 5. Progression-free survival in the tissue positive cohort, compared with the cfDNA positive cohort. cfDNA, cell-free circulating tumor DNA. 

Up to 45% of patients with advanced NSCLC have an actionable biomarker.6 Clinical studies repeatedly demonstrate that gene-targeted therapies improve overall response rates and progression-free survival versus immunotherapy or chemotherapy.7-13 Relying on tissue alone can delay the full potential of liquid biopsy as part of a personalized medicine strategy for treating NSCLC. In fact, in up to 30 percent of patients with solid tumors, insufficient results from tissue biopsy delay or prevent optimal treatment, at a time when time is of the essence.14-16  The results of the SLLIP study offer oncologists reassurance that using liquid biopsy not only provides the necessary speed, but also outcomes that are similar to those seen with tissue biopsy.

Despite potentially life-changing advances and guidelines, many patients with metastatic NSCLC are still being treated with immunotherapy or chemotherapy because first-line treatment decisions may have been made without the benefit of comprehensive genotyping. Current treatment guidelines by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology Clinical Practice call for broad genetic profiling in advanced non–small cell lung cancer, to facilitate optimal targeted therapy selections by the care team. The SLLIP study demonstrates the non-inferiority of cfDNA versus tumor tissue-based genotyping for the detection of clinically-actionable biomarkers. Now, more than ever, there is little reason for any NSCLC patient not to undergo Comprehensive Genomic Profiling so that they can receive rapid, optimal treatment and the longest possible progression-free survival time.


  1. Rolfo C, Mack P, Scagliotti GV, Aggarwal C, Arcila ME, Barlesi F, Bivona T, Diehn M, Dive C, Dziadziuszko R, Leighl N, Malapelle U, Mok T, Peled N, Raez LE, Sequist L, Sholl L, Swanton C, Abbosh C, Tan D, Wakelee H, Wistuba I, Bunn R, Freeman-Daily J, Wynes M, Belani C, Mitsudomi T, Gandara D. Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer. J Thorac Oncol. 2021 Oct;16(10):1647-1662. doi: 10.1016/j.jtho.2021.06.017. Epub 2021 Jul 8. PMID: 34246791.
  2. Palmero R, Taus A, Viteri S, et al. Biomarker Discovery and Outcomes for Comprehensive Cell-Free Circulating Tumor DNA Versus Standard-of-Care Tissue Testing in Advanced Non–Small-Cell Lung Cancer. JCO Precision Oncology. 2021;5: 93-102.
  3. 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. doi: 10.1158/1078-0432.CCR-19-0624.
  4. 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. doi:10.1001/jamaoncol.2018.4305
  5. Gyawali B, West H Plasma vs Tissue Next-Generation Sequencing in Non–Small Cell Lung Cancer—Either, Both, or Neither? JAMA Oncol. 2019;5(2):148–149.doi:10.1001/jamaoncol.2018.4304.
  6. Nature. 2014 July 31; 511(7511): 543–550. doi:10.1038/nature13385.
  7. 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.
  8. 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.
  9. 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.
  10. Camidge DR, Dziadziuszko R, Peters S, et al. Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion 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.
  11. Accessed January 26,2021.
  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.
  14. Hagemann IS, Devarakonda S, Lockwood CM, et al. Clinical Next-Generation Sequencing in Patients with Non–Small Cell Lung Cancer. Cancer. 2015;121:631-639.
  15. Parsons HA, Beaver JA, Cimino-Mathews A, et al. Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer. Cancer Res. 2017;23(2); 379–386.
  16. Wyatt AW, Annala M, Aggarwal R, et al. Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer. J Natl Cancer Inst. 2018;110(1):djx118