Axel Bex, MD, Netherlands Cancer Institute, Amsterdam, the Netherlands, reviews results from the multi-center, double-blinded, phase 3 IMmotion010 trial investigating atezolizumab monotherapy as an adjuvant treatment for patients with renal cell carcinoma and an increased risk of recurrence after resection.

The study showed that while the safety profile of atezolizumab was manageable, there was no improvement in clinical outcomes with atezolizumab when compared to placebo for this patient population.

These results were first presented at the 2022 European Society of Medical Oncology (ESMO) Congress.

Transcript:

My name is Axel Bex. I'm a urologist at the Netherlands Cancer Institute and also at the Royal Free Hospital in London. We're here at ESMO 2022 in Paris, where I gave a presentation on the IMmotion010 study.

IMmotion010 is a randomized controlled study on atezolizumab as adjuvant therapy versus placebo in patients with increased risk of recurrence after resection of the renal cell carcinoma. As you may know, patients do have a certain risk of recurrence, which is depending on tumor stage in grades and other factors, and which may be as high as 70% in the 5 years after resection.

Now, several trials have already been performed in the era of FGFR-targeted therapy with, for example, sunitinib, sorafenib, axitinib. Only sunitinib was approved in the United States, but not in Europe, for treatment because of a DFS [disease-free survival] benefit at that time. In the S-TRAC trial, none of these studies showed an overall survival benefit. With a change to immune checkpoint inhibitor therapy, several other trials were performed, and as you know, with KEYNOTE-564 the PD-1 inhibitor pembrolizumab was approved in the United States and Europe for adjuvant therapy.

Atezolizumab is a PD-L1 inhibitor that is approved in multiple tumor types, which was the basis for the rationale at the time we did the trial. Now when the IMmotion010 trial was designed, it was actually the first one. Therefore, it's also the longest running, with the longest follow-up. IMmotion010 was a randomized, controlled, multi-center trial, which included 778 patients. They were randomized one-to-one to atezolizumab versus placebo. Key eligibility criteria included increased to a high risk of recurrence by TNM [staging system], and clear cell or sarcomatoid component.

I'd like to point out that we tried to include a higher risk by making it mandatory that patients with the pT3a stage have at least a firm grade 3 to 4, and as in KEYNOTE, a metastasectomy group was included that included patients after synchronous metachronous disease presentation. What differed from KEYNOTE was that these patients required the recurrence in the metachronous setting that was not earlier than 12 months, because we tried to avoid the rapid progressors by making this selection.

Patients were stratified due to tumor stage, expression of PD-L1 on tumor infiltrating immune cells, and per region. The primary endpoint of the study was investigator-assessed disease-free survival in the intention-to-treat population, and key secondary endpoints were overall survival and the expression of PD-L1 for DFS in the intention-to-treat population. After a median follow up of 44.7 months, 332 events had occurred, which triggered the primary analysis, which was pre-specified, and that was based on a calculation that would, if there were a difference, would've had enough power to demonstrate an 0.7 hazard ratio. The disease-free survival estimates were by Kaplan-Meier methodology, and all the data were based on the data cut-off date on the 3rd of May, 2022. Patient demographics and baseline characteristics were well balanced. Roughly, the majority of patients had an ECOG performance score of 0, had predominant clear cell histology, and presented with tumor stages pT2a and pT3a. Importantly, there were 60% approximately in both arms that expressed PD-L1 on immune cells, and the M1 NED [no evidence of disease] population was capped at 14% and that was about the distribution in both arms.

Unfortunately, the primary endpoint was not met at the pre-specified primary endpoint analysis. There was no evidence that atezolizumab reduced the risk of recurrence and death versus placebo. The hazard ratio was 0.93 with the P-value of 0.5, and the 24-month disease-free survival estimate was 67% for atezolizumab and 65% for placebo. Overall survival was not met, was immature at that time of the analysis. But again, here, there was no evidence that atezolizumab reduced the risk of deaths from any cause. The hazard ratio was 0.97 in this population and will be followed up for further results. Safety profile was as expected, and was consistent for the known profile of atezolizumab.

In conclusion, atezolizumab did not change our outcome parameters in comparison to placebo. It was well tolerated, and there's certain subgroups that warrant further analysis such as the PD-L1 expressing subgroup, and potentially patients with sarcomatoid. Thank you.

Source:

Bex A, Uzzo R, Karam JA, et al. IMmotion010: Efficacy and safety from the phase III study of atezolizumab (atezo) vs placebo (pbo) as adjuvant therapy in patients with renal cell carcinoma (RCC) at increased risk of recurrence after resection.” Presented at ESMO Congress; September 9-13, 2022; Paris, France. Abstract LBA66.