PFS extension with immunotherapy + chemotherapy in urothelial cancer

Patients with metastatic urothelial cancer had longer progression-free survival (PFS) when treated with first-line immunotherapy and chemotherapy instead of chemotherapy alone, according to late-breaking results of the IMvigor130 trial [1].

IMvigor130 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). IMvigor130 is the first trial to test the combination of chemotherapy and immunotherapy in patients eligible and ineligible for chemotherapy.

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

In an interim analysis, median overall survival was 16.0 vs 13.4 months in Arms A and C, respectively (HR 0.83; 95% CI 0.69–1.00; P=0.027) and 15.7 vs 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%. Adverse events leading to treatment withdrawal occurred in 34%, 6%, and 34% of patients in Arms A, B, and C, respectively.

Compared with chemotherapy alone, chemotherapy plus atezolizumab improved the median time to progression of metastatic tumours by 2 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 with chemotherapy.

Presenting author Dr Enrique Grande (MD Anderson Cancer Centre Madrid, Spain), said the adverse effects from combined chemotherapy and immunotherapy were consistent with studies in other solid tumours. “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, Dr Ignacio Durán (Hospital Universitario Marques de Valdecilla-IDIVAL, Spain) cautioned that this improvement in PFS may be insufficient for regulatory approval at this stage, but said the data look promising. Dr Durán also noted that the observed complete responses were around twice as likely with the combination compared with 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, compared with 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.

1. Grande E et al. ESMO Congress 2019. Abstract LBA14_PR.

Posted on 26 November, 201918 March, 2024