1960O - Identification of bladder cancer patients that could benefit from early post-cystectomy immunotherapy based on serial circulating tumour DNA (ctDNA) testing: Preliminary results from the TOMBOLA trial

Background

The gold standard treatment of non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Despite this intense treatment, approximately 50% of the patients develop metastases within the first 2 years of follow-up. Adjuvant immunotherapy is recommended for selected patients at high risk for recurrence after cystectomy, whereas the remaining patients will only be treated at the time of visible recurrence. A more personalised identification of patients that could benefit from early immunotherapy is based on detection of circulating tumour DNA (ctDNA) during follow-up.

Methods

The TOMBOLA trial is an ongoing national, multicentre, non-randomized, interventional study in Denmark where patients undergoing NAC and RC because of non-metastatic MIBC (cT2-4aN0-1M0) are monitored with serial tumour informed ctDNA testing in the postoperative period. If the patient is ctDNA+ at any time point, an additional CT scan is done and Atezolizumab is initiated irrespective of imaging results. ctDNA-patients receive immunotherapy upon detection of metastases on imaging irrespectively of conventional risk groups.

Results

Of the first 153 patients, 87 (57%) were ctDNA+ post-RC (75% were detected < 4 months post RC). The median positive lead time over metastases identified by CT-scans (n=17; 20% of ctDNA+) was 43 days (range -13-501 days). Of the ctDNA- patients, only 2 (3%) developed metastases on CT-scan during follow-up. Interim primary endpoint data (response to immunotherapy measured from ctDNA and CT-scans) will include approximately 100 patients (clinical cutoff in August 2024).

Conclusions

Serial measurements of ctDNA following NAC and RC is a highly specific method to identify patients that might benefit from early immunotherapy at a time of minimal metastatic disease. To our knowledge this is the first report of clinical trial data where serial ctDNA measurements were used to guide treatment decisions in bladder cancer.

Clinical trial identification

NCT04138628.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Aarhus University, Novo Nordisk Foundation, Neye Foundation, Danish Ministry of Health.

Disclosure

J. Bjerggaard Jensen: Non-Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Research Grant: Ferring; Financial Interests, Personal, Advisory Board: Olympus, Janssen. L. Dyrskjot: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Roche. All other authors have declared no conflicts of interest.