The FDA approved atezolizumab (Tecentriq) to treat advanced or metastatic urothelial carcinoma on May 18, 2016, and metastatic non-small cell lung cancer (NSCLC) on October 18, 2016. Atezolizumab was approved for patients with either of these cancers who experience worsening of their disease during or after treatment with platinum-based chemotherapy. However, those with NSCLC who have epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase tumor (ALK) aberrations should first fail appropriate therapies before starting atezolizumab.1 Patients with urothelial cancer or NSCLC who have recurrence of their cancer after treatment have very poor prognosis. Both urothelial cancer and NSCLC cells express programmed death ligand 1 (PD-L1), a transmembrane protein. PD-L1 binds to programmed death 1 (PD-1) on the surface of T lymphocytes, which inhibits cytotoxic T-cell activity, T-cell proliferation, and cytokine production.1 Atezolizumab works by binding and inhibiting the action of PD-L1 which allows the immune system to help eradicate the cancer. Atezolizumab is a first-in-class medication and the only FDA-approved drug that targets PD-L1. It is also the first new drug in two decades that may be used to treat bladder cancer.
Atezolizumab was approved for urothelial carcinoma based on the results of the IMvigor 210 study.2 IMvigor 210 was an open-label, multicenter, single-arm, phase 2 trial that enrolled 315 patients with inoperable locally advanced or metastatic urothelial carcinoma in which the cancer was progressing following platinum-based chemotherapy. Three hundred and ten patients received 1200 mg atezolizumab given IV on day 1 of a 21-day cycle. Efficacy was assessed by an independent review of a facility-assessed overall response rates (ORR) (according to Response Evaluation Criteria in Solid Tumors v1.1) and an investigator-assessed ORR dependent on immune-modified RECIST.
The IMvigor 210 study found that 15% of patients responded to treatment with atezolizumab (95% confidence interval [CI], 11-20, p=0.0058): 5% of all patients achieved complete response (CR) and 10% achieved partial response (PR).2 The median duration of response was not determined despite a median follow-up time of 11.7 months. A subgroup analysis using modified RECIST criteria found patients who displayed ≥5% expression of PD-L1 in tumor infiltrating cells had better outcomes with atezolizumab than those with <5% PD-L1 expression. One hundred patients with ≥5% expression had an ORR of 27%, with CR 8% and PR 19% (95% CI, 19-37, p<0.0001), whereas 107 patients with ≥1% but <5% expression had an ORR of 17%, with CR 6% and PR 11%. The remaining 103 patients with <1% expression had an ORR of 13%, with CR 2% and PR 11%.
Atezolizumab was approved to treat NSCLC based on results of both a phase 2 study (POPLAR, n=287) and a phase 3 study (OAK, n=850).3 These international, multicenter, open-label studies randomized patients with advanced or metastatic NSCLC patients who progressed after previous treatment. In a 1:1 ratio patients were assigned to receive either 1200mg IV atezolizumab or 75mg/m2 IV docetaxel.4 In each case the infusion was given once every 3 weeks and both studies used overall survival (OS) as their primary endpoint.