scholarly journals Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH)

2017 ◽  
Vol 35 (24) ◽  
pp. 2781-2789 ◽  
Author(s):  
Solange Peters ◽  
Scott Gettinger ◽  
Melissa L. Johnson ◽  
Pasi A. Jänne ◽  
Marina C. Garassino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Independent Review

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti–programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non–small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1–expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility–assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility–assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1–selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab.

scholarly journals First-line pembrolizumab in programmed death ligand 1 positive non-small cell lung cancer

2019 ◽  
Vol 8 (7) ◽  
pp. 2514-2516
Author(s):  
Camille Travert ◽  
Pascale Tomasini ◽  
Arnaud Jeanson ◽  
Laurent Greillier ◽  
Fabrice Barlesi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals 38 Clinical validation of an image analysis assay for determining programmed death-ligand 1 (22C3) in non-small cell lung cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A39-A39
Author(s):  
Roberto Gianani ◽  
Will Paces ◽  
Elliott Ergon ◽  
Kristin Shotts ◽  
Vitria Adisetiyo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Image Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Clinical Validation ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

BackgroundDetermination of programmed death-ligand 1 (PD-L1) level in tumor by immunohistochemistry (IHC) is widely used to predict response to check point inhibitor therapy. In particular, the Dako PD-L1 (22C3) antibody is a common companion diagnostic to the monoclonal antibody drug Keytruda® (pembrolizumab) in non-small cell lung cancer (NSCLC).1 However, for the practicing pathologist, interpretation of the PD-L1 (22C3) assay is cumbersome and time consuming. Manual pathologist scoring also suffers from poor intra- and inter-pathologist precision, particularly around the cut-off point.2 In this clinical validation study, we developed an image analysis (IA) based solution to accurately and precisely score digital images obtained from PD-L1 stained NSCLC tissues for making clinical enrollment decisions.Methods10 NSCLC tissue samples were purchased from a qualified vendor and IHC stained for PD-L1; 4 of these samples had serial sections stained on two separate days. Stained slides were scanned at 20X magnification and analyzed using Flagship Biosciences’ IA solutions that quantify PD-L1 expression and separate tumor and stromal compartments. Resulting image markups of cell detection and PD-L1 expression were reviewed by an MD pathologist for acceptance. PD-L1 staining was evaluated by digital IA in the sample’s tumor compartment for Total Proportion Score (TPS,%). Assay specificity was defined by ≥ 90% of the tissue cohort exhibiting appropriate cell recognition (≥ 90% cells correctly recognized as determined by the pathologist), with ≤ 10% false positive rate for staining classification. Sensitivity was defined by ≥ 90% of the cohort exhibiting appropriate cell identification (≥ 90% cells correctly identified), with ≤ 10% false negative rate for staining classification. Accuracy was defined by the combination of sensitivity and specificity and precision was defined by concordance of the binned TPS (<1%, ≥ 1%, ≥ 50%) in ≥ 80% of the samples stained on multiple days.ResultsThe preliminary results show that IA can yield high analytical sensitivity, specificity, accuracy, and precision in the determination of the PD-L1 score. 100% of the tissue cohort met criteria for analytical specificity, sensitivity, and accuracy and 100% of the samples stained on multiple days met the precision criteria.ConclusionsThis data demonstrates the feasibility of an IA approach as applied to PD-L1 (22C3) scoring. Ongoing experiments include application of the developed 22C3 algorithm on a separate cohort of 20 NSCLC samples to determine the correlation of digital scoring and scoring obtained by three pathologists. Additionally, we will evaluate the precision obtained by digital scoring in relation to the intra- and inter-pathologist concordance.ReferencesIncorvaia L, Fanale D, Badalamenti G, et al. Programmed death ligand 1 (PD-L1) as a predictive biomarker for pembrolizumab therapy in patients with advanced non-small-cell lung cancer (NSCLC). Adv Ther 2019;36:2600–2617.Rimm DL, Han G, Taube JM, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non–small cell lung cancer. JAMA Oncol 2017;3:1051–1058.

scholarly journals Programmed Death-Ligand-1 Expression in Non-Small Cell Lung Cancer and Prognosis

2019 ◽  
Vol 36 (3) ◽  
pp. 184-189
Author(s):  
Songül Şahin ◽  
Şebnem Batur ◽  
Övgü Aydın ◽  
Tülin Öztürk ◽  
Akif Turna ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals Programmed Death Ligand-1 Immunohistochemistry— A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society

2016 ◽  
Vol 140 (4) ◽  
pp. 341-344 ◽  
Author(s):  
Lynette M. Sholl ◽  
Dara L. Aisner ◽  
Timothy Craig Allen ◽  
Mary Beth Beasley ◽  
Alain C. Borczuk ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Clinical Practice ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

The binding of programmed death ligand-1 and ligand-2 (PD-L1 and PD-L2) to PD-1 blocks T-cell–mediated immune response to tumor. Antibodies that target programmed death receptor-1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non–small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non–small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay–one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice.

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