AUA 2022: Prospective Evaluation of ctDNA in Detecting Early Progression on Immune Checkpoint Inhibitors in Patients With Advanced Genitourinary Cancers

(UroToday.com) The 2022 American Urological Association (AUA) Annual Meeting included a session on advanced kidney cancer and a presentation by Dr. Albert Jang discussing the prospective evaluation of circulating tumor DNA (ctDNA) in detecting early progression on immune checkpoint inhibitors in patients with advanced genitourinary cancers. Immune checkpoint inhibitors are approved for the treatment of advanced genitourinary malignancies, and tumor response to immune checkpoint inhibitors is largely based on conventional scans with known limitations. Liquid biopsy is an easy minimally invasive method to obtain tumor genetic information, such as ctDNA from the blood. Signatera is a commercially available personalized and tumor-informed mPCR NGS-based ctDNA test that is optimized to monitor tumor status in a patient’s blood sample. In this pilot study, Dr. Jang and colleagues investigated the serial ctDNA detection rate and the concordance of serial ctDNA changes with radiographic response rate of advanced genitourinary patients undergoing immune checkpoint inhibitor treatment. Their hypothesis was that serial ctDNA testing can accurately predict tumor response to immunotherapy compared with conventional scans.

 This study prospectively enrolled consecutive advanced genitourinary cancer patients treated with an immune checkpoint inhibitor-based regimen or monotherapy for at least 12 weeks, without evidence of disease progression, available ctDNA test result(s) and CT scans. To monitor ctDNA, patient blood was collected at the time of study entry and every 6-8 weeks until progressive disease occurred and/or until 2 years. Overall response rate (ORR) was assessed. The preliminary results were presented after a median follow up of 12 (range: 2.3-15.3) months.

 There were 12 patients in this study with a median age of 68 (range: 49-81) years, of which 75% had renal cell carcinoma, 17% urothelial carcinoma, and 8% had prostate cancer. All patients had at least one ctDNA test result at the time of data cut-off. Tumors were frequently PD-L1 negative (90%), and one patient had microsatellite instability with a median tumor mutational burden of 6 (range 3-25) mut/Mb. The immune checkpoint inhibitor regimens included 25% receiving monotherapy, 33% immune checkpoint inhibitors + immune checkpoint inhibitors combination therapy, and 42% immune checkpoint inhibitors + other regimen combination therapy. The median time on therapy was 6.5 months prior to first ctDNA test. Patients had a median number of 5 (range 1-6) ctDNA tests. The following table summarizes the ctDNA and overall response rate of the study cohort:

 

AUA 2022_Jang_0 

 

The detection rate was 50% and in all cases except one, ctDNA changes were concordant with ORR. One patient had progressive disease on imaging with an initial decline in ctDNA, that later increased. As follows is the Swimmers plot of these 12 stage IV patients through their immune checkpoint inhibitor treatment course:

 

AUA22_Jang_1.png

 

Dr. Jang concluded his presentation by discussing the prospective evaluation of ctDNA in detecting early progression on immune checkpoint inhibitors in patients with advanced genitourinary cancers with the following summary points:

  • In this pilot study, ctDNA was frequently detected in advanced genitourinary tumors and serial changes in ctDNA were concordant with staging scans to monitor disease response to immune checkpoint inhibitors
  • The Signatera ctDNA assay is a valid option to monitor immune checkpoint inhibitor treatment responses in advanced genitourinary malignancies
  • Future directions include continued follow-up of this patient cohort, and continuing to increase this cohort by expanding to other institutions

 

Presented by: Albert Jang, MD, Tulane Cancer Center, New Orleans, LA

Co-Authors: Ellen Jaeger, Grant Rauterkus, Alex Liberman, Isabelle Sussman, Malcolm Light, Minqi Huang, Charlotte Manogue, Sydney Caputo, Patrick Miller, Brian Lewis, Jodi Layton, Oliver Sartor, New Orleans, LA; Earle Burgess, Charlotte, NC; Tiffany Farmer, Hayley Widden, Carrie Flippen, Alexey Aleshin, San Carlos, CA; Claud Grigg, New York, NY; Pedro Barata, New Orleans, LA

 

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

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