Patients with metastatic urothelial cancer have longer progression free survival when treated with first-line immunotherapy and chemotherapy instead of chemotherapy alone, according to late breaking results of the IMvigor130 trial presented at the ESMO Congress 2019 in Barcelona, Spain.

Cisplatin based chemotherapy has been the standard first-line treatment for metastatic disease since the 1980s but up to half of patients are not fit enough to receive it, while those treated survive about 15 months on average. Immunotherapies such as the PD-L1 inhibitors atezolizumab and pembrolizumab are approved for patients ineligible or unresponsive to chemotherapy. IMvigor130 is the first trial to test the combination of chemotherapy and immunotherapy in patients eligible and ineligible for chemotherapy.

Compared to chemotherapy alone, chemotherapy plus atezolizumab improved the median time to progression of metastatic tumors by two months. Patients receiving the combination had an 18% reduced likelihood of progression. Interim analysis of overall survival showed a trend for improvement with the combination, but it was not statistically significant. There was also a trend for improved survival in patients with overexpression of PD-L1 who were treated with atezolizumab alone compared to chemotherapy.

Study author Dr. Enrique Grande, MD Anderson Cancer Centre Madrid, Spain, said the side-effects from combined chemotherapy and immunotherapy were consistent with studies in other solid tumors. "This is a new option for the upfront treatment of patients with metastatic urothelial cancer. Longer follow-up is needed on overall survival and we will continue to search for biomarkers to identify which patients respond best to this therapy."

Commenting on the results for ESMO, Dr. Ignacio Durán, Hospital Universitario Marques de Valdecilla-IDIVAL, Santander, Spain, cautioned that this improvement in progression free survival may be insufficient for regulatory approval at this stage, but said the data look promising.

Durán noted that the so-called "complete responses" – understood as relevant shrinkage or disappearance of cancer metastases – were around twice as likely with the combination compared to chemotherapy or immunotherapy alone. "This is remarkable. We are now eager to see if patients receiving the two therapies together live longer, and with a similar quality of life than those receiving chemotherapy and immunotherapy alone or sequentially. The interim analysis of overall survival seems to be promising, but data are immature: overall survival data are needed to consider the combination of chemotherapy and immunotherapy as a new standard of care," he said.

IMvigor130 (NCT02807636) randomly allocated 1,213 patients with metastatic urothelial cancer from 35 countries in a 1:1:1 ratio to atezolizumab plus platinum-based chemotherapy (Arm A), atezolizumab alone (Arm B), or placebo plus platinum-based chemotherapy (Arm C).

The coprimary efficacy endpoints were investigator-assessed progression free survival and overall survival (Arm A versus C) and overall survival (Arm B versus C). After a median follow-up of 11.8 months, median progression free survival was 8.2 months in Arm A and 6.3 months in Arm C. This corresponded to a statistically significant hazard ratio (HR) of 0.82 (95% confidence interval [CI] 0.70–0.96; P = 0.007).

In an interim analysis, median overall survival was 16.0 versus 13.4 months in Arms A and C, respectively (HR 0.83; 95% CI 0.69–1.00; P = 0.027) and 15.7 versus 13.1 months in Arms B and C, respectively (HR 1.02; 95% CI 0.83–1.24).
Objective response rates were 47%, 23% and 44% in Arms A, B and C, respectively. Complete response rates were 13%, 6% and 7% in Arms A, B and C, respectively. Adverse events leading to treatment withdrawal occurred in 34%, 6% and 34% of patients in Arms A, B and C, respectively. 

The study was funded by F. Hoffmann-La Roche, Ltd.