Jacek Jassem1, Filippo de Marinis2, Giuseppe Giaccone3, Alain Vergnenegre4, Carlos H Barrios5, Masahiro Morise6, Enriqueta Felip7, Cristina Oprean8, Young-Chul Kim9, Zoran Andric10, Simonetta Mocci11, Ida Enquist11, Kimberly Komatsubara11, Mark McCleland11, Hiroshi Kuriki11, Monette Villalobos11, See Phan11, David R Spigel12, Roy S Herbst13. 1. Medical University of Gdańsk, Gdansk, Poland. 2. European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy. 3. Weill Cornell Medical Center, New York, New York. 4. University Hospital Limoges, Limoges, France. 5. Centro de Pesquisa Clínica, Hospital São Lucas, PUCRS, Porto Alegre, Brazil. 6. Nagoya University Graduate School of Medicine, Nagoya, Japan. 7. Vall d'Hebron University Hospital, Barcelona, Spain. 8. Oncomed SRL and Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. 9. Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, South Korea. 10. Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia. 11. Genentech, Inc., South San Francisco, California. 12. Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee. 13. Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut. Electronic address: roy.herbst@yale.edu.
Abstract
INTRODUCTION: IMpower110 previously revealed significant overall survival (OS) benefit with atezolizumab versus chemotherapy in patients with treatment-naive EGFR- and ALK-negative (wild type [WT]) metastatic NSCLC with high programmed death-ligand 1 (PD-L1) expression (≥50% on tumor cells [TCs] or ≥10% on tumor-infiltrating immune cells [ICs], per SP142 immunohistochemistry assay; p = 0.0106). We present primary OS analyses in lower PD-L1 expression groups and an updated, exploratory analysis in the high PD-L1 expression group. METHODS: This open-label, phase 3 trial randomized patients with PD-L1 expression on greater than or equal to 1% of TC or IC to receive atezolizumab or platinum-based chemotherapy. The primary end point was OS, hierarchically tested in PD-L1 expression WT subgroups: first the high PD-L1 expression subgroup, then the high-or-intermediate PD-L1 expression subgroup (≥5% on TC or IC), and then the any PD-L1 expression subgroup (≥1% on TC or IC). RESULTS: The any PD-L1 expression WT population included 554 patients (excluded 18 EGFR- or ALK-positive patients). With 17 months' additional follow-up, OS improvement in the atezolizumab versus chemotherapy arm was not statistically significant in high-or-intermediate PD-L1 expression WT patients (n = 328; hazard ratio = 0.87, 95% confidence interval: 0.66-1.14, p = 0.3091; median = 19.9 versus 16.1 mo), precluding formal OS testing in any PD-L1 expression WT patients. Exploratory analysis in high PD-L1 expression WT patients (n = 205) revealed maintained OS benefit in the atezolizumab arm (hazard ratio = 0.76, 95% confidence interval: 0.54-1.09; median = 20.2 versus 14.7 mo). Updated safety data continued to favor atezolizumab. CONCLUSIONS: Statistical significance for OS was not revealed in the high-or-intermediate expression WT group, and, as a result, OS in the any PD-L1 expression WT group was not formally tested. No new safety signals were found. This updated analysis of IMpower110 supports using atezolizumab in treatment-naive, metastatic WT NSCLC with high PD-L1 expression.
INTRODUCTION: IMpower110 previously revealed significant overall survival (OS) benefit with atezolizumab versus chemotherapy in patients with treatment-naive EGFR- and ALK-negative (wild type [WT]) metastatic NSCLC with high programmed death-ligand 1 (PD-L1) expression (≥50% on tumor cells [TCs] or ≥10% on tumor-infiltrating immune cells [ICs], per SP142 immunohistochemistry assay; p = 0.0106). We present primary OS analyses in lower PD-L1 expression groups and an updated, exploratory analysis in the high PD-L1 expression group. METHODS: This open-label, phase 3 trial randomized patients with PD-L1 expression on greater than or equal to 1% of TC or IC to receive atezolizumab or platinum-based chemotherapy. The primary end point was OS, hierarchically tested in PD-L1 expression WT subgroups: first the high PD-L1 expression subgroup, then the high-or-intermediate PD-L1 expression subgroup (≥5% on TC or IC), and then the any PD-L1 expression subgroup (≥1% on TC or IC). RESULTS: The any PD-L1 expression WT population included 554 patients (excluded 18 EGFR- or ALK-positive patients). With 17 months' additional follow-up, OS improvement in the atezolizumab versus chemotherapy arm was not statistically significant in high-or-intermediate PD-L1 expression WT patients (n = 328; hazard ratio = 0.87, 95% confidence interval: 0.66-1.14, p = 0.3091; median = 19.9 versus 16.1 mo), precluding formal OS testing in any PD-L1 expression WT patients. Exploratory analysis in high PD-L1 expression WT patients (n = 205) revealed maintained OS benefit in the atezolizumab arm (hazard ratio = 0.76, 95% confidence interval: 0.54-1.09; median = 20.2 versus 14.7 mo). Updated safety data continued to favor atezolizumab. CONCLUSIONS: Statistical significance for OS was not revealed in the high-or-intermediate expression WT group, and, as a result, OS in the any PD-L1 expression WT group was not formally tested. No new safety signals were found. This updated analysis of IMpower110 supports using atezolizumab in treatment-naive, metastatic WT NSCLC with high PD-L1 expression.
Authors: Rianne D W Vaes; Kobe Reynders; Jenny Sprooten; Kathleen T Nevola; Kasper M A Rouschop; Marc Vooijs; Abhishek D Garg; Maarten Lambrecht; Lizza E L Hendriks; Marijana Rucevic; Dirk De Ruysscher Journal: Cancers (Basel) Date: 2021-12-13 Impact factor: 6.639