Second-line atezolizumab feasible for advanced urothelial carcinoma with comorbidity
medwireNews: Results from the SAUL study add support for the use of atezolizumab in patients with advanced urothelial or nonurothelial carcinoma of the urinary tract, including those with autoimmune disease and other comorbidities.
Reporting from the 2019 Annual European Association of Urology Congress in Barcelona, Spain, presenting author Axel Merseburger (University Hospital Schleswig-Holstein, Germany) said the study of “real-world patients” demonstrates that “atezolizumab is a tolerable and effective treatment, even in complex comorbid populations.”
The SAUL findings follow results from the IMvigor211 trial which showed fewer adverse events with the PD-L1 inhibitor than a physician’s choice of vinflunine, paclitaxel or docetaxel chemotherapy among patients who had progressed on platinum chemotherapy, albeit without a survival benefit.
The SAUL investigators enrolled 1004 patients from 32 countries who had previously been treated for locally advanced or metastatic urinary tract carcinoma; 98% had received platinum chemotherapy and the trial also included participants who had progression on non-platinum treatments.
However, the SAUL study was open to a broader range of patients than the IMvigor211 trial, including those with nonmeasurable disease, an ECOG performance status of 2, or stable central nervous system metastases, as well as individuals requiring ongoing steroid therapy or renal dialysis, and those with HIV infection or autoimmune disease.
In all, 997 patients received atezolizumab 1200 mg every 3 weeks for a median of five cycles over 2.8 months, and were followed up for a median 12.7 months.
The most common grade 3 or more severe adverse events were fatigue, asthenia, colitis and hypertension, all of which affected 1% of patients. There were seven (0.7%) treatment-related deaths, including two cases of dyspnoea, and single cases of colitis, intestinal perforation, respiratory failure, chronic kidney disease, and liver injury.
Just 6% of patients overall discontinued treatment because of adverse events and a similar pattern was found among the subgroups of patients with complex medical histories, affecting none of the 14 patients with CNS metastases, 3% of the 101 patients with a ECOG performance score of 2, 5% of the 40 patients using steroids, 7% of the 46 patients with renal impairment and 9% of the 35 patients with autoimmune disease.
Similarly, the discontinuation rate was 6% for the 643 SAUL patients who would have met the more rigorous entrance criteria for the IMvigor211 trial, the researchers say.
Overall survival in the intention-to-treat population was a median of 8.7 months, with 60% of patients alive at 6 months and 41% at 12 months. The corresponding values for progression-free survival were 2.2 months, and 29% and 17%.
A complete RECIST response occurred in 3% of patients and a partial response in 11%, giving an overall response rate of 13%. A further 26% of patients achieved stable disease, resulting in a disease control rate of 40%. The median duration of response was unreached at time of data analysis.
Among the SAUL patients who met IMvigor211 criteria for inclusion, median OS was 10.0 months, PFS was 2.3 months, and 46% of the subgroup were alive at 12 months. A complete response occurred in 4% of the patients and the overall response rate was 14%, with a median duration of response of 15.9 months.
“Efficacy overall and in the IMvigor211-like subgroup is consistent with previous pivotal anti-PD-L1/PD-1 [urothelial carcinoma] trials,” Merseburger said, referring to the atezolizumab arm of IMvigor211 and KEYNOTE-045 pembrolizumab arm.
He therefore concluded: “These results support use of atezolizumab in urinary tract carcinoma including in patients with limited treatment options.”
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