Atezolizumab extends PFS in metastatic urothelial cancer
BARCELONA, Spain — The addition of atezolizumab to chemotherapy prolonged PFS for patients with metastatic urothelial cancer, according to results of a randomized phase 3 study presented at European Society for Medical Oncology Congress.
An interim analysis showed the regimen conferred an improvement in OS that researchers characterized as clinically meaningful but not statistically significant.
“This is the biggest trial in bladder cancer in some time because it showed at least some efficacy in OS, whereas before all the clinical trials we have done came back negative or they came back with improved tolerability but no benefit in survival,” Enrique Grande, MD, head of the medical oncology service at The University of Texas MD Anderson Cancer Center and head of clinical research at the MD Anderson Foundation in Spain, told HemOnc Today. “This is the first time we have seen a combination show any kind of benefit in survival.”
The study included 1,213 patients with metastatic urothelial cancer.
Researchers assigned patients to one of three regimens: atezolizumab (Tecentriq, Genentech) — a monoclonal antibody designed to bind to PD-L1 — plus platinum-based chemotherapy (gemcitabine plus either cisplatin or carboplatin, n = 451), atezolizumab alone (n = 262), or placebo plus platinum-based chemotherapy (n = 400).
Atezolizumab was administered at 1,200 mg via IV on day 1 of each 3-week treatment cycle. Gemcitabine was dosed at 1,000 mg/m2 on day 1 and day 8. Carboplatin was dosed at area under the curve 4.5, and cisplatin was administered at 70 mg/m2 on day 1.
Tumors were assessed at baseline and every 9 weeks thereafter during the trial.
Investigator-assessed PFS and OS among patients treated with atezolizumab plus platinum-based chemotherapy compared with those who received placebo plus platinum-based chemotherapy, as well as OS per RECIST 1.1 criteria among patients assigned atezolizumab alone vs. those who received platinum chemotherapy alone, served as co-primary endpoints.
Median follow-up was 11.8 months.
Results showed median PFS of 8.2 months among patients assigned with atezolizumab and platinum-based chemotherapy compared with 6.3 months among patients assigned placebo and platinum-based chemotherapy (HR = 0.82; 95% CI, 0.7-0.96).
Median OS was 16 months among patients assigned atezolizumab plus platinum-based chemotherapy compared with 13.4 months for patients treated with placebo plus chemotherapy (HR = 0.83; 95% CI, 0.69-1). This result did not cross the prespecified interim efficacy boundary.
When researchers compared OS between patients who received atezolizumab alone compared with those who received placebo plus chemotherapy, they reported improved outcomes with atezolizumab in the intention-to-treat population (median, 15.7 months vs. 13.1 months; HR = 1.02; 95% Ci, 0.83-1.24) and patients with the highest PD-L1 expression based on tumor-infiltrating immune cells (not estimable vs. 17.8 months; HR = 0.68; 95% CI, 0.43-1.08).
Objective response rates were 47% among patients who received atezolizumab plus chemotherapy, 23% for patients who received atezolizumab alone, and 44% for patients treated with placebo and chemotherapy.
One-third of patients in both groups treated with chemotherapy withdrew due to adverse events, compared with 6% of patients treated with atezolizumab.
“I believe it is too early to know whether we will continue to see benefits for OS,” Grande told HemOnc Today. “We need more events to demonstrate the superiority. The trend looks promising, but we need a longer follow-up to know if we truly met this endpoint.” – by John DeRosier
Grande E, et al. Abstract LBA14. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.
Disclosure s : F. Hoffmann-La Roche funded this study. Grande reports research funding from, speakers’ bureau roles and consultant roles with Adacap, AstraZeneca, Eisai, European Neuroendocrine Tumor Society, EUSA Pharma, Ipsen, Lexicon, Merck Sharpe & Dohme, Molecular Templates Inc., Novartis, Pfizer, Roche and Sanofi Genzyme.