Median overall survival is the same for both malignancies, study results show.
Atezolizumab (Tecentriq) appears to have similar activity and safety in upper tract urothelial carcinoma as in the more common bladder urothelial cancer, according to exploratory analyses of the single-arm, multicenter SAUL study (NCT02928406).
The finding provides reassurance considering the expected worse outcomes in patients with upper urinary tract versus bladder urothelial carcinoma, said Cora N. Sternberg, MD, who presented the data at the 2020 Genitourinary Cancers Symposium in San Francisco.
Median overall survival (OS) was 8.3 months in patients with upper tract urothelial carcinoma compared with 8.8 months in those with bladder carcinoma, and the 1-year OS rates were 42% and 41%, respectively. At a data cutoff of September 16, 2018, 56% of the group with upper tract urothelial carcinoma and 55% with bladder carcinoma had died.
Median PFS of 2.2 months in both groups
The percentages with progression-free survival (PFS) events were 78% in the group with upper tract urothelial carcinoma and 79% in patients with bladder carcinoma. Median PFS was 2.2 months in both groups.
“It is thought that patients with upper tract tumors respond less well than those with bladder carcinoma, when, in fact, we found that the median OS for patients with upper tract cancer, many of whom had poor renal function or were ineligible for enrollment into registration trials, was exactly the same as that for patients with bladder tumors,” said Sternberg, professor of medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York. “We can say from this large single-arm study that it’s safe to treat both upper tract, renal pelvis and ureter, as well as bladder carcinoma with atezolizumab.”
Upper tract urothelial carcinoma tends to respond poorly to standard chemotherapy. Further, an analysis of 220 patients treated with atezolizumab, for whom biomarkers were evaluable, suggested worse outcomes in upper versus lower tract urothelial carcinoma, prompting the analysis presented at the symposium.
SAUL enrolled a broader population of patients with urinary tract carcinoma who were more representative of real-world practice compared with those typically enrolled in randomized phase 3 trials of immunotherapy.
Patients in SAUL had locally advanced/metastatic urothelial or nonurothelial carcinoma of the urinary tract. Patients enrolled could have poor clinical characteristics and/or immune-mediated conditions.
“The primary end point of the study was safety. We allowed patients in who are not normally allowed in the registration studies. We allowed in patients with immunologic disease or poor creatinine clearance, renal transplant patients, patients on steroids, and patients with brain metastases, for example,” Sternberg told Urology Times®.
Participants were treated with atezolizumab, 1200 mg intravenously every 3 weeks, until loss of efficacy, patient or investigator decision to withdraw from treatment, or death. The group with upper tract carcinoma consisted of 226 patients, 99 with ureteral carcinoma and 127 with renal pelvis carcinoma. They were followed for a median of 13.2 months. The bladder carcinoma subgroup had 749 patients, who were followed for a median of 12.2 months.
Baseline characteristics in the subgroups were generally similar. However, a numerically smaller proportion of the group with upper tract urothelial cancer had no prior lines of therapy for metastatic disease compared with the bladder cancer subgroup (30% vs 41%) and a numerically smaller proportion reported being current or former smokers (59% vs 70%, respectively).
Treatment was ongoing at data cutoff in 21% of patients with upper tract urothelial carcinoma (26% with ureteral carcinoma, 17% with renal pelvis carcinoma) and in 22% with bladder carcinoma. The median duration of treatment was 2.1 months in patients with upper tract urothelial carcinoma versus 2.9 months in patients with bladder carcinoma.
The incidence of grade 3 or higher adverse effects (AEs) was 42% in the upper tract urothelial carcinoma group and 46% in the bladder carcinoma group. Urinary tract infection was more common in the bladder carcinoma group compared with the upper tract urothelial carcinoma group (17% vs 11%, respectively). Arthralgia was more common in patients with ureteral versus renal pelvis carcinoma (12% vs 6%, respectively).
Rates of grade 3 or higher treatment-related AEs were 14% in the group with upper tract urothelial carcinoma versus 13% in those with bladder carcinoma. AEs leading to treatment discontinuation occurred in 6% of both groups.
Disclosures: F. Hoffmann-La Roche & Co. provided funding for the study. Sternberg has received honoraria from Astellas Pharma, AstraZeneca, Ipsen, Janssen, Pfizer, and Sanofi. She is a consultant/adviser for Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Eisai, Incyte, Ipsen, Medscape, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, and UroToday. For full disclosures, go to bit.ly/sauldisclosures.