FDA Approves Atezolizumab for Extensive-Stage Small Cell Lung Cancer
On March 18, 2019, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
Approval was based on IMpower133 (NCT02763579), a randomized (1:1), multicenter, double-blind, placebo-controlled trial in 403 patients with ES-SCLC who received no prior chemotherapy for extensive stage disease and had ECOG performance status zero or one.
Patients were randomized to one of the following:
- Atezolizumab 1,200 mg and carboplatin AUC 5 mg/ml per minute on day one and etoposide 100 mg/m2 via IV on days one, two, and three of each 21-day cycle for a maximum of four cycles, followed by atezolizumab 1,200 mg once every three weeks until disease progression or unacceptable toxicity.
- Placebo and carboplatin AUC 5 mg/ml per minute on day one and etoposide 100 mg/m2 via IV on days one, two, and three of each 21-day cycle for a maximum of four cycles, followed by placebo once every three weeks until disease progression or unacceptable toxicity.
Major efficacy outcome measures were overall survival (OS) and progression-free survival (PFS) as assessed by investigator per RECIST 1.1 in the intent-to-treat population. Median OS was 12.3 months (10.8, 15.9) for patients receiving atezolizumab with chemotherapy and 10.3 months (9.3, 11.3) for those receiving placebo with chemotherapy (hazard ratio [HR] = 0.70; 95% CI = 0.54, 0.91; p = 0.0069).
Median PFS was 5.2 months (4.4, 5.6) compared with 4.3 months (4.2, 4.5) in the atezolizumab and placebo arms, respectively (HR = 0.77; 0.62, 0.96; p = 0.0170).
The most common adverse reactions reported in ≥ 20% of patients who received atezolizumab in IMpower133 were fatigue/asthenia, nausea, alopecia, constipation, and decreased appetite.
The recommended atezolizumab dose for patients with ES-SCLC is 1,200 mg via IV for 60 minutes every three weeks. When administered on the same day, atezolizumab should be administered prior to chemotherapy. If the first infusion is tolerated, all subsequent infusions may be delivered for 30 minutes.
FDA granted this application priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home) or by calling 800-FDA-1088.
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