Researchers who treated a group of patients with bladder cancer with the immunotherapy atezolizumab after they had undergone surgery have found that patients whose blood contained circulating tumor DNA (ctDNA) responded very well to the treatment. The study was presented at the European Association of Urology Annual Congress (EAU22).
The research was part of the phase III IMvigor010 trial, which investigated whether giving atezolizumab for up to 1 year to patients following bladder removal improved the patients’ survival prospects, compared to patients who received no further treatment after surgery but were placed in an observation group. Part of that trial involved patients’ levels of ctDNA being measured after surgery, as well as during further treatment or observation.
Role of ctDNA
Although the trial found no significant difference in overall survival between the two groups in the intention-to-treat population, researchers noticed that a subgroup of patients who were ctDNA-positive showed a marked improvement when they were given atezolizumab. These benefits included significantly higher disease-free survival and overall survival than patients in the observation group. This effect wasn’t seen in ctDNA-negative patients.
In addition, the researchers also found that patients who were ctDNA-positive but became ctDNA-negative after treatment with atezolizumab ultimately had a particularly good prognosis.
Jürgen Gschwend, MD, Chairman 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’ve 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 consequent drug activity is linked to ctDNA status, and that high-risk patients will benefit, that could in time change the standard treatment pathway—and ultimately bring down the average cost of ctDNA analysis.”
Commentary
Morgan Rouprêt, MD, PhD, Chairman of the European Section of Onco-Urology of the EAU, said, “The field of personalized medicine, using not only clinical but molecular indicators, is just around the corner. So, analyzing ctDNA is very interesting. It is 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 will be the upcoming IMvigor011 study, which has been redesigned as a consequence of these results. With 500 participants, the trial will further evaluate the use of ctDNA sampling and will compare atezolizumab against placebo in only ctDNA-positive patients postsurgery.
Dr. Rouprêt added, “Unlike in prostate cancer, where we can measure prostate-specific antigen as a marker of cancer, until now, we haven’t had anything we can use for bladder cancer. But these robust findings show that ctDNA has great potential as a sophisticated tool to monitor patients and choose their most effective treatment. The progress of the IMvigor011 study will be watched closely by specialists for a greater assessment of the use of atezolizumab in [patients with] bladder cancer.”
