Robert Jones, MD, University of Glasgow, UK, shares results and insights from the phase 2 ATLANTIS trial, evaluating maintenance cabozantinib following chemotherapy for patients with metastatic urothelial carcinoma who were negative for DNA repair biomarkers.

These findings were presented at the 2022 ASCO Annual Meeting.

Transcript:

Hi, my name is Rob Jones. I'm a genitourinary medical oncologist in Glasgow, in the UK. I recently presented some data from a trial called ATLANTIS, which is a trial amongst patients with advanced urothelial cancers. That's cancers of the bladder and related structures. ATLANTIS is actually a platform trial, and it was designed actually to ask precision medicine questions in bladder cancer, the idea being that patients undergoing first line combination, platinum-based chemotherapy undergo biomarker testing during that period where they're receiving conventional chemotherapy. And then at the end of chemotherapy, the patients who are still benefiting, that is the patients who have stable disease, partial or complete response, then are invited to take part in one of a suite of randomized trials, according to their biomarker status.

Now, during the design of a trial, our patient partners were, although very enthused about the idea of precision medicine and participating in precision medicine trials, also advised us strongly that we should have an option for patients who are biomarker negative, so that all patients potentially have the option of being randomized.

Actually, the data represented here are the data from patients who were negative for biomarkers, in this case, biomarkers of DNA repair. Those patients were offered randomization to a PARP inhibitor or a placebo, or patients with a positive androgen receptor test who were randomized between enzalutamide or a placebo. This was a trial of the rest of the patients. So there's some negative selection going on here.

And patients were randomized either to receive cabozantinib or placebo. Now, cabozantinib is a multi-targeted tyrosine kinase inhibitor. It's quite widely used to treat renal cancer and one or two other cancers. And its principle targets of vascular endothelial growth factor receptors, but with some activity also against other tyrosine kinases, which may be relevant in urothelial cancer, in particular axle met and met.

Patients who were enrolled within four to 10 weeks of their last dose of chemotherapy, and they continued on treatment until progression. The primary endpoint was progression-free survival. This was a randomized phase two signal searching study. So it was not designed to change practice. It was designed to rule out the prospect of a phase three trial that had a high alpha, a one-sided alpha a 0.2.

To cut a long story short, there was no difference between the two arms of the trial. In terms of progression-free survival, there was no detectable difference and certainly no difference. The hazard ratio was slightly in favor of cabozantinib, but the P value was greater than that 0.2 level. Similarly, there was no difference in terms of overall survival, which was the secondary end point.

The conclusion of this study was that in unselected patients, there would be no value in performing a randomized phase three trial of the mono agent in this setting.

Now, the other thing to say about this trial is that actually it was closed early. And the principle reason it closed early was because the standard of care changed. At the time the trial was conceived and enrolled, the standard of care was surveillance followed by immunotherapy on progression. And the trial was closed early when maintenance avelumab therapy was licensed.

As a secondary comment, that although the control arm of this trial was placebo, that would no longer be considered an ethical control arm for trials such as this.

Does this have any implications for our practice? Well, yes. The implication would be that we should certainly not be offering these patients mono agent cabozantinib as a maintenance treatment.

Source:

Jones RJ, Hussain SA, Birtle AJ, et al. A randomised, double blind, phase II clinical trial of maintenance cabozantinib following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS cabozantinib comparison. Presented at: American Society of Clinical Oncology; June 3-7, 2022. Chicago, IL, and virtual. Abstract LBA4505.