Atezolizumab translates into survival benefit for bladder cancer patients with ctDNA positivity

Researchers who treated a group of postoperative bladder cancer patients with the immunotherapy drug atezolizumab found that patients whose blood contained circulating tumor DNA (ctDNA) responded very well to the treatment.

The research will be presented today at the annual conference of the European Association of Urology (EAU22), in Amsterdam.

The study was part of a larger phase III study, IMvigor010, that looked at whether giving atezolizumab to patients for up to one year after bladder removal surgery improved patients’ survival, compared to a group that did not receive further treatment after surgery. received, but in an observation group. Part of that study involved measuring patients’ ctDNA levels after surgery and during further treatment or observation.

Although the study found no significant difference in overall survival between the two groups in the intention-to-treat population, the researchers noted that a subset of patients who were ctDNA positive showed marked improvement when they received atezolizumab. These benefits include significantly higher disease-free survival and significantly higher overall survival than the observation group. This effect was not seen in ctDNA negative patients.

In addition, the researchers also found that patients who were ctDNA positive, but then turned to ctDNA negative after treatment with atezolizumab, ended up having a particularly good prognosis.

ctDNA consists of DNA fragments secreted from cancer cells and tumors found in the bloodstream. Sometimes known as a ‘liquid biopsy’, it has emerged as a promising, minimally invasive biomarker in clinical oncology, but is not yet widely used as part of a standard cancer detection and treatment tool. It involves tumor-specific gene sequencing for each patient, so time-consuming and currently relatively expensive.

Professor Gschwend, chair of the Department of Urology at the Technical University of Munich, said: “We already knew that patients who are ctDNA positive have a poor prognosis compared to those who are ctDNA negative. But this is the first time we have have been able to show that with immunotherapy we can actually change the course of the disease depending on a patient’s ctDNA status.”

He continued: “If we can prove that the resulting drug activity is related to ctDNA status, and that high-risk patients benefit, that could eventually change the standard treatment route – ultimately lowering the average cost of ctDNA analysis. †

Professor Morgan Roupret, Chair of the European Section for Onco-urology of the European Association of Urology, said: “The field of personalized medicine, using not only clinical but also molecular indicators, is just around the corner. Analyzing ctDNA is therefore very interesting. It’s relatively easy to do with new technology and it means we can select a subset of patients who are likely to respond.”

The next step is the upcoming IMvigor 011 study, which has been redesigned as a result of these results. With 500 participants, the study will further evaluate the use of ctDNA sampling and compare atezolizumab to placebo in ctDNA-positive patients only, after surgery.

Professor Roupret added: “Unlike prostate cancer, where we can measure PSA as a marker of the cancer, we haven’t had anything to date that we can use for bladder cancer. But these robust findings show that ctDNA has great potential as an advanced tool to monitor patients and choose their most effective treatment. The progress of the IMvigor 011 trial will be closely monitored by specialists to better assess the use of atezolizumab in patients with bladder cancer.”