Sandra Horning, MD
The FDA has granted a priority review to a supplemental new drug application (sNDA) for the use of the PD-L1 inhibitor atezolizumab (Tecentriq) in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma (mUC) as a frontline therapy or following progression occurring ≥12 months after neoadjuvant or adjuvant chemotherapy.
Data from 310 patients were evaluable. The patients had been heavily pretreated, with 40% of patients undergoing 2 or more prior systemic regimens in the metastatic setting and 74% of patients receiving previous cisplatin-based chemotherapy.
Atezolizumab was administered at 1200 mg intravenously on the first day of each 21-day cycle until no further clinical benefit was demonstrated. Median treatment duration was 12 weeks (range, 0-46 weeks). The coprimary study endpoints were ORR, as assessed by central review and the investigators, both by modified RECIST v1.1. Secondary endpoints included duration of response, PFS, OS, and safety.
At a median follow-up of 14.4 months, ORR was 14.8% (95% CI, 11.1-19.3; n = 46/310) in all comers, 26% (95% CI, 17.7-35.7; n = 26/100) in patients with PD-L1 expression ≥5%, and 9.5% (95% CI, 5.9-14.3; n = 20/210) in those with PD-L1 expression <5%. In a subgroup of 59 patients from the IMvigor 210 study who progressed after neoadjuvant or adjuvant platinum-based chemotherapy, the ORR was 22% (95% CI, 12.3-34.7).
Complete response rates in the overall, higher–PD-L1, and lower–PD-L1 groups were 5.5%, 12%, and 2.4%, respectively. Partial response rates were 9.4%, 14%, and 7.1%, respectively. The median duration of response was 12.7 months (range, 2.1+ to 12.7) in the higher PD-L1 population, and had not yet been reached in either the overall group or the lower PD-L1 cohort.
Overall, 10 patients discontinued atezolizumab due to adverse events (AEs). The most common grade 3/4 adverse events included urinary tract infection (9%), anemia (8%), fatigue (6%), dyspnea (4%), and hematuria (3%). There were 3 patient deaths, which were related to sepsis, pneumonitis or intestinal obstruction.
The accelerated approval is contingent on results from an ongoing confirmatory phase III study, IMvigor 211 (NCT02302807), which is comparing atezolizumab with chemotherapy in patients with locally advanced or metastatic urothelial bladder cancer who have progressed on at least 1 prior platinum-containing regimen.
- Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67-76.
- Hoffman-Censits JH, Grivas P, Van Der Heijden MS, et al. IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). J Clin Oncol 34, 2016 (suppl 2S; abstr 355).
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