Abstract
BackgroundThis 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. MethodsPD-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. ResultsIn 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. ConclusionsDespite 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.
Highlights
Docetaxel was a long-standing standard of care for the secondor third-line treatment of advanced non–small cell lung cancer (NSCLC) based on improved overall survival (OS) in controlled phase III studies.[1,2,3] The introduction of checkpoint inhibitors targeting the programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1) pathway has dramatically altered the management of NSCLC, with shown OS benefits in patients with advanced disease, both in first and subsequent lines of therapy.[4]
When defined by the SP142 assay, prevalence rates for PD-L1– positive (TC1/2/3 or IC1/2/3) subgroups were similar between the SP142-intention to treat (ITT) population (56%)[11] and 22C3-BEP (62%) (Table 2)
It should be noted that the prevalence rates for the 22C3-defined PD-L1–positive subgroup (47%) were slightly lower than previously reported in the published literature (22C3 tumor proportion score (TPS) ≥ 1% PD-L1 prevalence is approximately 57% of the ITT population[26,40]). This is unlikely to be explained by pre– cut slide–stability issues and epitope deterioration because samples in this study were stored and prepared in line with manufacturer instructions for the 22C3 assay. This current analysis from OAK provides further support that, each assay has a different scoring algorithm and differing levels of sensitivity, both SP142 and 22C3 assays are predictive for atezolizumab benefit at validated PD-L1 expression thresholds in patients with NSCLC
Summary
Docetaxel was a long-standing standard of care for the secondor third-line treatment of advanced non–small cell lung cancer (NSCLC) based on improved overall survival (OS) in controlled phase III studies.[1,2,3] The introduction of checkpoint inhibitors targeting the programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1) pathway has dramatically altered the management of NSCLC, with shown OS benefits in patients with advanced disease, both in first and subsequent lines of therapy.[4]. Atezolizumab has been approved as a second- or later-line treatment for patients with metastatic NSCLC.[12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
