TY - JOUR
T1 - Comparison of SP142 and 22C3 Immunohistochemistry PD-L1 Assays for Clinical Efficacy of Atezolizumab in Non–Small Cell Lung Cancer
T2 - Results From the Randomized OAK Trial
AU - Gadgeel, Shirish
AU - Hirsch, Fred R.
AU - Kerr, Keith
AU - Barlesi, Fabrice
AU - Park, Keunchil
AU - Rittmeyer, Achim
AU - Zou, Wei
AU - Bhatia, Namrata
AU - Koeppen, Hartmut
AU - Paul, Sarah M.
AU - Shames, David
AU - Yi, Jing
AU - Matheny, Christina
AU - Ballinger, Marcus
AU - McCleland, Mark
AU - Gandara, David R.
N1 - Funding Information:
The authors thank the patients and the patients’ families. Medical writing assistance for this manuscript was provided by Anusha Bolonna, PhD, of Health Interactions and funded by F. Hoffmann-La Roche Ltd.
Funding Information:
Dr. Gadgeel reports personal fees from Genentech/Roche, AstraZeneca, Merck, Bristol Myers Squibb, Novartis, Daichii-Sanyko, Boehringer-Ingelheim, Xcovery, Jazz Pharmaceuticals, Pfizer, and Janssen, outside the submitted work. Dr. Hirsch reports scientific advisory board for Genentech/Roche, Merck, Bristol Myers Squibb, Novartis, AstraZeneca/Daiichi, Regeneron/Sanofi, and Amgen, outside the submitted work. Dr. Kerr reports personal fees from AbbVie, Amgen, AstraZeneca, Archer Diagnostics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Debiopharm, Diaceutics, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, and Roche Diagnostics/Ventana, outside the submitted work. Dr. Barlesi reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda, outside the submitted work. Dr. Park has nothing to disclose. Dr. Rittmeyer reports grants from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Pfizer, Roche, and Novartis, outside the submitted work. Dr. Zou reports employment from Genentech, outside the submitted work. Dr. Bhatia reports employment from Genentech, outside the submitted work. Dr. Koeppen reports employment from Genentech, outside the submitted work. Dr. Paul reports employment from Genentech, outside the submitted work. David Shames reports employment from Genentech and stock ownership from Roche, outside the submitted work. Dr. Yi reports employment and spousal employment from Genentech and stock ownership from Roche, outside the submitted work. Dr. Matheny reports employment from Genentech, during the conduct of the study, and employment from Genentech, outside the submitted work. Dr. Ballinger reports employment from Genentech and stock ownership from Roche, outside the submitted work. Dr. McCleland reports employment from Genentech, outside the submitted work. Dr. Gandara reports personal fees and institutional grants from Genentech, outside the submitted work.
Funding Information:
This work was supported by F. Hoffmann-La Roche Ltd and Genentech Inc, a member of the Roche Group. The sponsor was involved in study design; collection, analysis and interpretation of data, and development and submission of this report. Editorial support, funded by the sponsor, was provided by an independent medical writer under the guidance of the authors.
Publisher Copyright:
© 2021 The Authors
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - Biomarker-evaluable population
KW - Inter-assay concordance
KW - Overall survival
KW - Programmed death ligand 1
KW - Progression-free survival
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U2 - 10.1016/j.cllc.2021.05.007
DO - 10.1016/j.cllc.2021.05.007
M3 - Article
C2 - 34226144
AN - SCOPUS:85109065638
SN - 1525-7304
VL - 23
SP - 21
EP - 33
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 1
ER -