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Research article
Multi-Analyte Liquid Biopsies for Treatment Guidance in Advanced Refractory Cancers: Findings of the LIQUID IMPACT Trial
Dadasaheb Akolkar
Datar Cancer Genetics
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4434-488X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
LIQUID IMPACT (CTRI/2019/02/017548) is a single arm, open label, phase II/III study to evaluate the feasibility of providing therapeutic guidance in cancers based on non-invasive interrogation of circulating tumor analytes in peripheral blood (Encyclopedic Liquid Biopsy: eLB). The study enrolled patients with solid organ cancers where the disease had progressed following systemic therapy failure, where no (further) viable standard of care (SoC) therapy options were available, and where invasive biopsies to obtain tumor tissue (for molecular profiling) were contraindicated.
Methods
Encyclopedic Liquid Biopsy (eLB) interrogated gene alterations in cell-free tumor DNA (ctDNA), and differentially expressed genes in exosomal mRNA. eLB also evaluated Circulating Tumor Associated Cells for expression of therapeutically relevant cell-surface signaling receptors as well as the chemoresistance profile towards systemic anticancer agents. Patients who received personalized combination therapy regimens based on eLB findings were evaluated radiologically to determine response to treatment, Objective Response Rate (ORR) and Quality of Life (QoL).
Results
At the time of submission of this manuscript, Partial Response (PR) was observed in 14 of 43 patients evaluable per protocol (ORR = 32.6%). Majority of patients reported stable to improved QoL.
Conclusion
The present study demonstrated that refractory cancers have latent vulnerabilities which can be identified via non-invasive eLB to design personalized label- and organ-agnostic treatment regimens to yield meaningful treatment benefit.
Trial registration
Clinical Trial Registry – India, CTRI/2019/02/017548 [Registered on: 02/08/2019] - http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=31265&EncHid=&modid=&compid=%27,%2731265det%27; Trial Registered Prospectively.
Keywords
Liquid biopsy, Circulating Tumor Associated Cells, immunocytochemistry, Objective Response Rate, progression free survival, exosomes, ctDNA, Non-invasive
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Research article
Multi-Analyte Liquid Biopsies for Treatment Guidance in Advanced Refractory Cancers: Findings of the LIQUID IMPACT Trial
Dadasaheb Akolkar
Datar Cancer Genetics
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4434-488X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 19 Aug, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
LIQUID IMPACT (CTRI/2019/02/017548) is a single arm, open label, phase II/III study to evaluate the feasibility of providing therapeutic guidance in cancers based on non-invasive interrogation of circulating tumor analytes in peripheral blood (Encyclopedic Liquid Biopsy: eLB). The study enrolled patients with solid organ cancers where the disease had progressed following systemic therapy failure, where no (further) viable standard of care (SoC) therapy options were available, and where invasive biopsies to obtain tumor tissue (for molecular profiling) were contraindicated.
Methods
Encyclopedic Liquid Biopsy (eLB) interrogated gene alterations in cell-free tumor DNA (ctDNA), and differentially expressed genes in exosomal mRNA. eLB also evaluated Circulating Tumor Associated Cells for expression of therapeutically relevant cell-surface signaling receptors as well as the chemoresistance profile towards systemic anticancer agents. Patients who received personalized combination therapy regimens based on eLB findings were evaluated radiologically to determine response to treatment, Objective Response Rate (ORR) and Quality of Life (QoL).
Results
At the time of submission of this manuscript, Partial Response (PR) was observed in 14 of 43 patients evaluable per protocol (ORR = 32.6%). Majority of patients reported stable to improved QoL.
Conclusion
The present study demonstrated that refractory cancers have latent vulnerabilities which can be identified via non-invasive eLB to design personalized label- and organ-agnostic treatment regimens to yield meaningful treatment benefit.
Trial registration
Clinical Trial Registry – India, CTRI/2019/02/017548 [Registered on: 02/08/2019] - http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=31265&EncHid=&modid=&compid=%27,%2731265det%27; Trial Registered Prospectively.
Figure 1
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Figure 3