In patients with previously treated non-small cell lung cancer (NSCLC), atezolizumab increases overall survival compared with docetaxel, regardless of programmed death ligand 1 (PD-L1) status, histology, and subsequent immunotherapy, according to a new study published in the Journal of Thoracic Oncology.
"In clinical trials conducted with immunotherapy, the benefit to patients is usually sustained over time," write the investigators, led by first author Julien Mazieres, MD, PhD, Professor of Respiratory Medicine at Toulouse University Hospital in Toulouse, France. "However, response rates and progression-free survival cannot give a complete picture of the full benefit of immunotherapy treatment as well as the entire patient journey. Thus, an analysis of long-term survival and other outcomes is needed to assess the benefit of treatment in these patients."
The study analyzed the results of two clinical trials: POPLAR, a phase 2 trial, and OAK, a phase 3 trial. The two studies enrolled 287 and 1,225 patients, respectively, with locally advanced or metastatic NSCLC whose disease progressed after platinum-containing chemotherapy. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients in both trials were randomized to receive intravenous atezolizumab 1,200 mg or docetaxel 75 mg/m2 once every 3 weeks, until disease progression or loss of clinical benefit.
Atezolizumab significantly increased median overall survival in both POPLAR (12.6 vs 9.7 months) and OAK (13.3 vs 9.8 months) compared with docetaxel. Four-year overall survival rates were also higher with atezolizumab in POPLAR (14.8% vs 8.1%) and OAK (15.5% vs 8.7%). In both trials, the survival benefit of atezolizumab was consistent across all PD-L1 expression and histology subgroups. Among four-year survivors in the atezolizumab group, treatment-related grade 3/4 adverse events occurred in 27% of patients in POPLAR and 16% of patients in OAK.
"In conclusion, long-term follow-up from these two randomized phase 2 and 3 clinical trials suggests a consistently greater survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC, regardless of the level of PD-L1 expression or histology," write Dr. Mazieres and colleagues. "Atezolizumab has shown a consistent and manageable safety profile with fewer treatment-related adverse events and fewer treatment discontinuations due to adverse events than docetaxel. Most patients continued atezolizumab or received immunotherapy beyond progression, indicating the potential for long-term clinical benefit from these therapies."
For More Information
Mazieres J, Rittmeyer A, Gadgeel S, et al (2020). Atezolizumab vs docetaxel in pretreated patients with non-small cell lung cancer: final results from the randomized phase II POPLAR and phase III OAK clinical trials. J Thorac Oncol. [Epub ahead of print] DOI:10.1016/j.jtho.2020.09.022
Fehrenbacher L, Spira A, Ballinger M, et al (2016). Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet, 387(10030):1837-1846. DOI:10.1016/S0140-6736(16)00587-0
Fehrenbacher L, von Pawel J, Park K, et al (2018). Updated efficacy analysis including secondary population results for OAK: a randomized phase III study of atezolizumab versus docetaxel in patients with previously treated advanced non-small cell lung cancer. J Thorac Oncol, 13(8):1156-1170. DOI:10.1016/j/jtho.2018.04.039
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