2018 GU CANCERS SYMPOSIUM: Adding Immunotherapy to Standard Treatment Slows Growth of Advanced Kidney Cancer—With Fewer Side Effects
In a phase III clinical trial of patients with previously untreated metastatic renal cell cancer combining the immunotherapy atezolizumab (Tecentriq) with the targeted therapy bevacizumab (Avastin) delayed cancer growth by about 3 months longer than sunitinib, another targeted therapy. The benefit of atezolizumab plus bevacizumab was greater for patients with programmed cell death ligand 1 (PD-L1)–positive tumors. These findings will be presented by Motzer et al at the upcoming 2018 Genitourinary Cancers Symposium in San Francisco (Abstract 578).
Atezolizumab is an immune checkpoint inhibitor that blocks the PD-L1 protein on the surface of tumor cells, allowing the immune system to recognize and attack those cells. Bevacizumab and sunitinib are targeted agents that block the growth of blood vessels to the tumor, thereby limiting its growth.
“The side effects of atezolizumab plus bevacizumab were decidedly less harsh than sunitinib. And because progression-free survival was also better, I am confident that this relatively easy-to-administer combination will be a strong treatment choice in all medical practices,” said lead study author Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center.
About the Study
IMmotion151 is the first randomized, phase III combined immunotherapy with bevacizumab trial in patients with untreated metastatic renal cell cancer. Starting in 2015, sites worldwide enrolled 915 adults who were randomly assigned to receive either atezolizumab plus bevacizumab intravenously every 3 weeks, or oral sunitinib daily for 4 weeks followed by 2 weeks off treatment.
“With the introduction of checkpoint inhibitors, clinicians started looking at combinations of these medicines with antiangiogenic medicines like bevacizumab,” said Dr. Motzer. “Bevacizumab may affect the local immune response in the tumor and help prime the response of tumor and immune cells to immune-system activators like atezolizumab.”
Key Findings
For the analysis, the researchers grouped patients according to PD-L1 expression on immune cells in the tumor (ie, tumor-infiltrating immune cells). Tumors that had the PD-L1 protein detected on the surface of at least 1% of those immune cells were considered PD-L1–positive, and all other tumors were considered PD-L1–negative.
The study had co-primary endpoints:
- Investigator-assessed progression-free survival in the PD-L1–positive group
- Overall survival in the group of all enrollees, also called the intention-to-treat population
At a median follow-up of 15 months, patients in the PD-L1–positive group treated with atezolizumab and bevacizumab had a 26% lower chance of the cancer worsening than those who received sunitinib; the median progression-free survival was also 3.5 months longer (median = 11.2 months in the atezolizumab-plus-bevacizumab group vs. 7.7 months in the sunitinib group).
In the intention-to-treat group, a benefit of atezolizumab plus bevacizumab was also observed, though it was more modest. Those treated with atezolizumab and bevacizumab had a 17% lower chance of cancer worsening, with a median progression-free survival of 2.4 months.
The difference in overall survival between the two treatment regimens was not statistically significant at this early interim analysis. Overall survival data are still immature, and the authors are planning an updated analysis as more data accrue.
Treatment-related side effects were less frequent in the atezolizumab-and-bevacizumab group, occurring in 40% of patients compared to 54% of patients in the sunitinib group. Twelve percent of patients in the atezolizumab-and-bevacizumab group and 8% in the sunitinib group stopped at least one treatment component due to treatment-related side effects during the trial.
“For an aggressive cancer like this, where less than 20% of people survive 5 years after diagnosis, we think a 3.5-month-longer progression-free survival, given the tolerability for this new combination treatment regimen, is an important development,” said Dr. Motzer.
The study will continue to assess overall survival as specified by protocol as well as secondary endpoints. In addition, the researchers collected tumor tissue and will look at molecular profiles to try to tease out markers, in addition to PD-L1, in the people who responded best to the combination therapy. Dr. Motzer said the researchers may look at novel therapies that could be added to atezolizumab so they could devise treatments to boost survival odds even higher.
Expert Commentary
“Adding immunotherapy to existing targeted therapies has shown promising results in recent clinical trials. We’re pleased to see validation of this approach through this large trial in advanced kidney cancer, a disease that remains incurable for most patients,” said ASCO Expert Sumanta K. Pal, MD.
This study was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
