Matt D. Galsky, MD, on Urothelial Carcinoma: New Study Results on Atezolizumab, Platinum, and Gemcitabine

IMvigor130 is a phase 3 study that compared three treatment arms for the first line treatment of metastatic urothelial cancer. Treatment with platinum-based chemotherapy, treatment with atezolizumab the PD-L1 inhibitor, or the combination of platinum-based chemotherapy plus atezolizumab. The study had co-primary endpoints, progression-free survival comparing chemo versus chemo plus atezo, and overall survival that was a co-primary endpoint as well. The progression-free survival endpoint has previously been reported in the trial MAP that endpoint showing a PFS benefit with chemo plus atezo versus chemo alone. Overall survival has been assessed at multiple interim analysis, and then at ASCO GU 2023, the final analysis for overall survival. The hazard ratio for overall survival was 0.85 with an upper bound of the 95% competence interval of one, and it didn't meet the pre-specified threshold for statistical significance. So chemotherapy plus atezolizumab improves progression-free survival, but not overall survival based on the threshold specified in the statistical analysis plan. The study did show however, that when you look at the type of platinum-based chemotherapy that patients received, if they received cisplatin-based chemotherapy, there did seem to be a beneficial effect combining with atezolizumab versus carboplatin-based chemotherapy. This is hypothesis generating data, but it really highlights the potential importance of the chemotherapy backbone when we combine with immune checkpoint blockade and there's immunologic data that support that clinical finding that's being used to generate hypotheses to be tested in the next generation of clinical trials. Because chemotherapy plus atezolizumab did not improve overall survival compared to chemotherapy alone, this does not impact standard of care as it has in other solid tumors where we see combination of chemotherapy plus immune checkpoint blockade becoming a standard of care. But based on the patient population enrolled and the mix of chemotherapy backbones with cisplatin and carboplatin, there is hypothesis generating data that will be tested in future studies to determine whether or not the choice of chemotherapy backbone actually makes the difference when combining chemotherapy and immune checkpoint blockade.