The FDA has expanded the approval of atezolizumab (Tecentriq®, Genentech, Inc.) to include adults with untreated metastatic non-small cell lung cancer (NSCLC) with high expression of programmed death ligand-1 (PD-L1). High PD-L1 expression is defined as PD-L1 staining on at least 50% of tumor cells or tumor-infiltrating immune cells covering at least 10% of the tumor area. In addition, the FDA has approved a companion diagnostic device, the Ventana PD-L1 (SP142) Assay (Ventana Medical Systems, Inc.), for determining eligibility for treatment with atezolizumab
The atezolizumab approval was based on IMpower110 (NCT02409342), a phase 3 trial which enrolled 572 patients with chemotherapy-naive stage IV NSCLC and PD-L1 expression of at least 1%; 205 patients had high tumor PD-L1 expression. Eligible patients had no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic aberrations. Patients were randomized in a 1:1 ratio to receive either atezolizumab 1,200 mg every three weeks or platinum-based chemotherapy, consisting of cisplatin or carboplatin, until unacceptable toxicity or disease progression. The study's primary end point was overall survival.
In patients with high PD-L1–expressing tumors, atezolizumab significantly increased median overall survival compared with platinum-based chemotherapy (20.2 months vs 13.1 months) at a median follow-up of 15.7 months. There were no statistically significant differences in overall survival for the other two subgroups with lower levels of PD-L1 expression. Atezolizumab produced a longer median progression-free survival (8.1 months vs 5.0 months) and a higher confirmed overall response rate (38% vs 29%).
Adverse reactions, including fatigue, decreased appetite, nausea, pyrexia, dyspnea, constipation, cough, and diarrhea, occurred in 60.5% of patients receiving atezolizumab, compared with 85.2% of patients receiving chemotherapy. Grade 3/4 adverse reactions were also less frequent for atezolizumab (12.9% vs 44.1%).
"IMpower110 met the primary overall survival end point with statistically significant and clinically meaningful improvement in the [high PD-L1–expressing] population," concluded the trial's investigators, led by first author David Spigel, MD, Chief Scientific Officer of Sarah Cannon Research Institute at HCA Healthcare in Nashville, Tennessee, in the abstract of their interim analysis presentation last October at the European Society for Medical Oncology (ESMO) 2019 Congress. "The safety profile favored [atezolizumab], with no new or unexpected safety signals seen."
The recommended dose of atezolizumab for patients with high PD-L1–expressing metastatic NSCLC is 840 mg every two weeks; 1,200 mg every three weeks; or 1,680 mg every four weeks. Atezolizumab should be administered intravenously over 60 minutes.
For More Information
Spigel D, de Marinis F, Giaccone G, et al (2019). IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC. Ann Oncol (ESMO Congress Abstracts), 30(suppl_5):v851-v934. Abstract 6256. DOI:10.1093/annonc/mdz394
Clinicaltrials.gov (2020). A study of atezolizumab (MPDL3280A) compared with a platinum agent (cisplatin or carboplatin) + (pemetrexed or gemcitabine) in participants with stage IV non-squamous or squamous non-small cell lung cancer (NSCLC) [IMpower110]. NLM identifier: NCT02409342.
US Food & Drug Administration (2020). FDA approves atezolizumab for first-line treatment of metastatic NSCLC with high PD-L1 expression. Available at: https://www.fda.gov/drugs/ resources-information-approved-drugs/fda-approves-atezolizumab-first-line-treatment-metastatic-nsclc-high-pd-l1-expression?utm_campaign=Oncology%205-18-2020%20atezolizumab&utm_medium=email&utm_source=Eloqua
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