Sandra Horning, MD
Atezolizumab (Tecentriq) demonstrated consistent safety and efficacy with prior studies of the PD-L1 inhibitor in patients with locally advanced or metastatic urothelial carcinoma (mUC), including clinically relevant subgroups reflective of real-world clinical practice, according to results from the phase IIIb SAUL study, which were presented at the 2019 European Association of Urology Meeting.
In SAUL, investigators evaluated atezolizumab in 997 patients with locally advanced or mUC. A subgroup of patients, which correspond to the patient population of the pivotal phase III IMvigor211 study, was defined as “IMvigor211-like” (n = 643). Patient populations evaluated that resembled that of real-world clinical practice included those with renal impairment, an ECOG performance status of 2, treated asymptomatic central nervous system (CNS) metastases, and stable controlled autoimmune disease.
“SAUL is the largest prospective safety study of a cancer immunotherapy in metastatic urothelial carcinoma and provides clinicians with valuable information about Tecentriq in a real-world setting," said Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech (Roche), the manufacturer of atezolizumab. “We remain committed to improving outcomes for people living with this devastating illness and we look forward to sharing data in the future from our ongoing phase III studies in early and metastatic disease.”
The FDA initially granted atezolizumab an accelerated approval as a treatment for patients with locally advanced or mUC whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery, in May 2016, based on findings from the phase II IMvigor210 study.
However, in May 2017, atezolizumab missed the phase III IMvigor211 trial’s primary endpoint of improving overall survival (OS) as a second-line treatment for patients with locally advanced or mUC. This trial was intended to confirm the findings of the phase II IMvigor210 study. Patients in IMvigor211 had previously treated mUC and progressed during or following a platinum-based regimen.
In the prospective, open-label, single-arm, multicenter, SAUL study, atezolizumab was evaluated as a second- to fourth-line therapy for patients with locally advanced or metastatic urothelial carcinoma (95%) or non-urothelial carcinoma (5%) of the urinary tract, as well as the PD-L1 inhibitor’s efficacy and potential biomarkers.
To be eligible for enrollment, patients had to mirror the IMvigor211-like population and and have renal impairment, an ECOG performance status of 2, treated asymptomatic CNS metastases, or stable controlled autoimmune disease. The primary endpoint of the trial was safety; secondary endpoints included OS, progression-free survival (PFS), overall response rate (ORR), and duration of response (DoR).
Results showed that the tolerability of atezolizumab was consistent with the known safety profile of the PD-L1 inhibitor; all-grade adverse events (AEs) were 88% and 90% in the intent-to-treat (ITT) and IMvigor211-like populations, respectively. Grade 3/4 AEs were reported in 43% of the ITT population compared with 41% of the IMvigor211-like subgroup. Additionally, treatment-related grade ≥3 AEs occurred in 13% of patients in both groups, with the most common reported AEs being fatigue, asthenia, colitis, and hypertension (1% each). AEs that led to treatment discontinuation occurred in 6% of both patients overall and in the IMvigor211-like group.
Moreover, at a median follow-up of 12.7 months, additional data showed that the median OS was 10 months (95% CI, 8.8-11.9) in the IMvigor211-like population compared with 8.7 months (95% CI 7.8–9.9) in the overall population. Moreover, the 12-month OS rate was 41% (95% CI, 38%-44%) in the ITT group compared with 46% (95% CI, 41%-50%) in the IMvigor211-like subgroup.
The median progression-free survival was 2.2 months (95% CI, 2.1-2.4) and 2.3 months (95% CI, 2.2-2.6) in the overall and IMvigor211-like subgroup, respectively. Additionally, the ORRs were 13% and 14%, and complete response rates were 3% and 4%, in the ITT and IMvigor211-like groups, respectively.
The SAUL study is ongoing and further subgroup analyses will also be presented at upcoming medical meetings.
Roche to Present Results of the Largest Safety Study of its Kind With Tecentriq (Atezolizumab) In Patients With Metastatic Bladder Cancer. Genentech (Roche). Published March 18, 2019. https://bit.ly/2F6Am7a. Accessed March 18, 2019.