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FDA Approves Atezolizumab for Lung Cancer

Jason M. Broderick @jasoncology
Published: Tuesday, Oct 18, 2016

Sandra Horning, MD

Sandra Horning, MD

The FDA has approved atezolizumab (Tecentriq) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) who have progressed after a platinum-containing regimen and an FDA-approved targeted therapy for those patients harboring EGFR or ALK abnormalities. 

The approval is based on multiple clinical trials, the largest being the phase III OAK trial, which was presented at the 2016 ESMO Congress.1 In the study, atezolizumab reduced the risk of death by 26% compared with docetaxel in patients with advanced NSCLC following the failure of platinum-based chemotherapy. The median overall survival (OS) was improved by 4.2 months with the PD-L1 inhibitor versus chemotherapy. The survival benefit with atezolizumab was observed regardless of PD-L1 status or histology.

“Tecentriq is a new option to help people with this type of previously treated metastatic lung cancer, regardless of PD-L1 expression, live longer than chemotherapy,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, the developer of atezolizumab, said in a statement. “Tecentriq is the first and only approved cancer immunotherapy designed to target the PD-L1 protein, which may play an important role in the way the medicine works.”

The international, open-label randomized phase III OAK trial included 1225 patients with locally advanced or metastatic NSCLC—regardless of histology or PD-L1 status—who progressed during or after platinum-containing chemotherapy. Patients were randomized in a 1:1 ratio to 75 mg/m2 of intravenous docetaxel or 1200 mg of intravenous atezolizumab every 3 weeks.

Patient demographics were well balanced between the 2 arms at baseline. The median patients age was 64 years, 61% of patients were male, 18% had never smoked, and 25% had received 2 prior lines of therapy. Patients had an ECOG performance status of 0 (37%) or 1 (63%). Among patients randomized to docetaxel, 17% received immunotherapy as their next treatment.

The coprimary endpoints of the trial were OS in the entire study population and in a PD-L1–defined subgroup. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR). The primary efficacy assessment included only the initial 850 randomized patients, and the secondary efficacy analysis will include data from all 1225 randomized patients.

In the intent to treat population (N = 850), the median OS was 13.8 months in the atezolizumab arm (n = 425) versus 9.6 months in the docetaxel arm (n = 425; HR, 0.74; 95% CI, 0.63-0.87; P = .0004). The PFS was 2.8 months versus 4 months (HR, 0.95), respectively. The ORR and DoR were 13.6% versus 13.4%, and 16.3 versus 6.2 months, respectively.

In nonsquamous patients, the median OS was 15.6 months in the atezolizumab group (n = 313) compared with 11.2 months in the control group (n = 315; HR, 0.73; 95% CI, 0.60-0.89). Among patients with squamous histology, the median OS was 8.9 months in the atezolizumab cohort (n = 112) versus 7.7 months on the docetaxel arm (n = 110; HR, 0.73; 95% CI, 0.54-0.98).

Regarding PD-L1 status, PD-L1–positive patients (TC1/2/3 or IC1/2/3) had expression on at least 1% of their tumor cells (TC) or tumor-infiltrating immune cells (IC). PD-L1 negative patients (TC0 or IC0) had less than 1% expression on their TC and IC.

Among the PD-L1–positive group, the median OS was 15.7 months in the atezolizumab arm (n = 241) compared with 10.3 months in the control arm (n = 222; HR, 0.74; 95% CI, 0.58-0.93; P = .0102). Among PD-L1–negative patients, the median OS was 12.6 months in the atezolizumab cohort (n = 180) versus 8.9 months in the docetaxel group (n = 199; HR, 0.75; 95% CI 0.59-0.96; P = .0205).

The safety profile with atezolizumab in the OAK trial was consistent with adverse event (AE) outcomes observed in previous studies of the PD-L1 inhibitor. AEs occurring more frequently in the atezolizumab arm included musculoskeletal pain (11% vs 4% with docetaxel) and pruritus (8% vs 3%).

The rate of grade 3/4 AEs was lower in the atezolizumab arm versus the control arm at 15% versus 43%, respectively. No treatment-related deaths occurred in the atezolizumab cohort compared with 1 in the docetaxel arm.

The phase II BIRCH2 and POPLAR3,4 studies also demonstrated the efficacy of atezolizumab in this setting. In the BIRCH study, responses were observed in up to 27% (P = .0001) of previously treated patients with NSCLC who had the highest levels of PD-L1 expression

The open-label, single-arm study enrolled 667 patients with stage IIIB/IV or recurrent NSCLC who did not have active CNS metastases. Patient characteristics were balanced across cohorts; the median age was 64 years, 35% were ECOG PS 0, 28% had squamous NSCLC, and 17% of patients were never-smokers. EGFR and KRAS mutations were identified in 327 and 177 patients overall, respectively.


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