1. Comparison of SP142 and 22C3 Immunohistochemistry PD-L1 Assays for Clinical Efficacy of Atezolizumab in Non–Small Cell Lung Cancer: Results From the Randomized OAK Trial
- Author
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Fred R. Hirsch, Sarah M. Paul, Keunchil Park, C. Matheny, Achim Rittmeyer, Jing Yi, Wei Zou, Marcus Ballinger, Mark McCleland, Fabrice Barlesi, Keith M. Kerr, Shirish M. Gadgeel, Hartmut Koeppen, David R. Gandara, David S. Shames, and Namrata Bhatia
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Population ,Antineoplastic Agents ,Subgroup analysis ,Docetaxel ,Antibodies, Monoclonal, Humanized ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Atezolizumab ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Progression-free survival ,education ,Lung cancer ,Immune Checkpoint Inhibitors ,Retrospective Studies ,education.field_of_study ,business.industry ,Hazard ratio ,medicine.disease ,Immunohistochemistry ,Confidence interval ,Treatment Outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
BACKGROUND This phase III OAK trial (NCT02008227) subgroup analysis (data cutoff, January 9, 2019) evaluated the predictive value of 2 PD-L1 IHC tests (VENTANA SP142 and Dako 22C3) for benefit from atezolizumab versus docetaxel by programmed death ligand 1 (PD-L1) status in patients with previously treated metastatic non-small cell lung cancer. METHODS PD-L1 expression was assessed prospectively with SP142 on tumor cells (TC) and tumor-infiltrating immune cells (IC) and retrospectively with 22C3 using a tumor proportion score (TPS) based on TC membrane staining. Efficacy was assessed in the 22C3 biomarker-evaluable population (22C3-BEP) (n = 577; 47.1% of SP142-intention-to-treat population) and non-22C3-BEP (n = 648) in PD-L1 subgroups (high, low, and negative) and according to selection by 1 or both assays. RESULTS In the 22C3-BEP, overall survival benefits with atezolizumab versus docetaxel were observed across PD-L1 subgroups; benefits were greatest in SP142-defined PD-L1-high (TC3 or IC3: hazard ratio [HR], 0.39 [95% confidence interval (CI), 0.25-0.63]) and 22C3-defined PD-L1-high (TPS ≥ 50%: HR, 0.56 [95% CI, 0.38-0.82]) and low (TPS, 1% to < 50%: HR, 0.55 [95% CI, 0.37-0.82]) groups. Progression-free survival improved with increasing PD-L1 expression for both assays. SP142 and 22C3 assays identified overlapping and unique patient populations in PD-L1-high, positive, and negative subgroups. Overall survival and progression-free survival benefits favored atezolizumab over docetaxel in double PD-L1-positive and negative groups; patients with both SP142- and 22C3-positive tumors derived the greatest benefit. CONCLUSIONS Despite different scoring algorithms and differing sensitivity levels, the SP142 and 22C3 assays similarly predicted atezolizumab benefit at validated PD-L1 thresholds in patients with non-small cell lung cancer.
- Published
- 2022
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