At the 2023 ASCO Genitourinary Cancers Symposium, Aristotelis Bamias, MD, National and Kapodistrian University of Athens, Athens, Greece, presented results from the IMvigor130 study, evaluating atezolizumab monotherapy vs platinum plus gemcitabine chemotherapy among previously untreated patients with locally advanced or metastatic urothelial carcinoma.

There was no statistically significant improvement of overall survival in the atezolizumab monotherapy arm vs the chemotherapy arm. However, further exploratory analyses suggested a benefit to overall survival with atezolizumab monotherapy for patients with high PD-L1 expression, especially those who are cisplatin-ineligible. Dr Bamias concluded, “the overall risk-benefit ratio still supports the use of atezolizumab monotherapy in first line for patients who are cisplatin-ineligible and have metastatic urothelial cancer with high PD-L1 expression.”

Transcript:

Good afternoon from Athens. My name is Aristotle Bamias. I'm Professor of Medical Oncology at the University of Athens and I'm affiliated to Attikon University Hospital. I will be presenting at the 2023 ASCO Genitourinary Cancers Symposium a late breaking abstract on overall survival analysis regarding the comparison between atezolizumab monotherapy and platinum/gemcitabine chemotherapy in the context of IMvigor130 study.

IMvigor130 study is a phase 3 clinical trial which enrolled patients with metastatic urothelial cancer who had not received any systemic therapy before for their metastatic disease. The trial randomized patients to receive either chemotherapy plus atezolizumab, which is an PD-L1 agent, atezolizumab alone, or platinum-gemcitabine chemotherapy plus placebo.

The trial had 2 co-primary efficacy endpoints and then there was a hierarchical analysis depending on whether the first 2 efficacy endpoints were met. The first efficacy endpoint was progression-free survival, which indeed was met as there was a significant prolongation of survival by adding atezolizumab to chemotherapy versus chemotherapy alone. Nevertheless, the second co-primary efficacy point, overall survival, comparing these 2 arms, atezolizumab plus chemotherapy versus chemotherapy alone, was not met and therefore the overall survival analyses I will present are not formal, but exploratory. The overall survival between arm B, which is atezolizumab monotherapy versus arm C, which was platinum-gemcitabine chemotherapy did not differ. They were very similar with 15.2 months for arm B and 13 months for arm C with hazard ratio of 0.98.

We also performed an exploratory analysis by PD-L1 status and cisplatin-ineligibility. Atezolizumab is approved in Europe as first-line treatment for patients with metastatic urothelial cancer, with high PD-L1-expression and patients who are cisplatin-ineligible. Clearly this is a population of special interest. We found that indeed patients with tumors with low PD-L1 expression, scored 0 or 1, show no difference in the overall survival between arms B and C. On the contrary, there seem to be a prolongation of overall survival in favor of atezolizumab monotherapy within the PD-L1 high expressors. This benefit was even more pronounced when the analysis was restricted to cisplatin-ineligible patients. In this case, median overall survival for cisplatin-ineligible patients with tumors expressing high PD-L1 was 18 months versus 10 months for chemotherapy alone with a hazard ratio of 0.56, while there was no difference when the PD-L1 expression in the tumors was low.

Looking at safety, the safety profile of atezolizumab remained favorable compared to that of chemotherapy. There were fewer treatment-related adverse events, fewer treatment-related serious adverse events. There was a higher rate of adverse events of special interest, that is events related to immunotherapy, but again, grade 3/4 events were only 10%. More importantly, fewer patients had to stop, interrupt, or dose modify treatment because of treatment-related adverse events.

Therefore, we conclude that atezolizumab monotherapy has similar overall survival to platinum-gemcitabine chemotherapy, but a better tolerated profile. It seems that PD-L1 expression can identify patients more likely to benefit by atezolizumab versus chemotherapy in first-line, especially within the cisplatin-ineligible population. Therefore, the overall risk-benefit ratio still supports the use of atezolizumab monotherapy in first-line for patients who are cisplatin-ineligible and have metastatic urothelial cancer with high PD-L1 expression. Thank you for listening to my presentation.

Source:

Bamias A, Davis ID, Galsky MD, et al. Final overall survival (OS) analysis of atezolizumab (atezo) monotherapy vs chemotherapy (chemo) in untreated locally advanced or metastatic urothelial carcinoma (mUC) from the Phase 3 IMvigor130 study. Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract LBA441