19 May Metastatic Bladder Cancer: Study Evaluates Combination of Checkpoint Blocker with Chemotherapy
MedicalResearch.com Interview with:
Matthew Galsky, MD
Icahn School of Medicine at Mount Sinai
New York, NY
MedicalResearch.com: What is the background for this study?
Response: Standard first-line treatment for metastatic urothelial (bladder) cancer has been platinum-based chemotherapy for decades. In 2016, atezolizumab, an immunotherapy that inhibits PD-L1, received accelerated approval by the FDA for the treatment of metastatic urothelial cancer for patients progressing despite prior platinum-based chemotherapy and this was followed by approvals for 4 additional PD-1 or PD-L1 inhibitors in this setting over the next couple years. With this first new drug class approved, representing the first new drugs approved for metastatic urothelial cancer for decades, logical question arose
(a) should we combine these drugs with platinum-based chemotherapy in the first-line metastatic treatment setting and
(b) is there a role to replace first-line chemotherapy with atezolizumab monotherapy. The IMvigor 130 trial was designed to address these questions.
The trial enrolled 1213 patients who were randomized to treatment with (a) atezolizumab plus platinum-based chemotherapy, (b) placebo + platinum-based chemotherapy, or (c) atezolizumab monotherapy. The trial employed a hierarchical analysis plan such that comparisons between arms for certain endpoints could only be formally tested if other the preceding comparisons demonstrated a significant improvement.
MedicalResearch.com: What are the main findings?
Response: Therefore, this first report of the study results includes the final analysis of progression-free survival between atezolizumab plus chemotherapy versus chemotherapy and the interim overall survival analysis of these treatment arms. The analysis of atezolizumab monotherapy versus chemotherapy was not formally testing given the point in the testing hierarchy but interim results for these arms were included as well.
The trial demonstrated a significant improvement in progression-free survival with atezolizumab + platinum-based chemotherapy versus chemotherapy with a hazard ratio of 0.82. The interim OS analysis also favored atezolizumab + platinum-based chemotherapy versus chemotherapy with a HR of 0.83 but the p value of 0.027 did not meet the pre-specified threshold for significance and the study in proceeding to the final OS analysis.
The survival curves for atezolizumab versus chemotherapy favor chemotherapy in the early portions of the curve but at approximately 10 months the curves cross.
MedicalResearch.com: What should readers take away from your report?
Response: This is the first randomized trial reporting results combining chemotherapy with immune checkpoint blockade in urothelial cancer versus chemotherapy alone or immune checkpoint blockade monotherapy versus chemotherapy. The primary PFS endpoint was met for the combination regimen and the OS results at the interim analysis also favor the combination arm. If confirmed by the final OS analysis, these results could support a regimen combining chemotherapy plus atezolizumab as a standard treatment approach for the first-line treatment of metastatic urothelial cancer.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future research should seek to define whether there are tumor characteristics that can help identify whether or not individual patients may be best treated with chemotherapy plus atezolizumab versus chemotherapy alone versus atezolizumab alone.
Any disclosures? I have served on advisory boards for Roche/Genentech.
Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial
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