E J Aguilar1, B Ricciuti1, J F Gainor2, K L Kehl1, S Kravets3, S Dahlberg3, M Nishino4, L M Sholl5, A Adeni1, S Subegdjo1, S Khosrowjerdi2, R M Peterson2, S Digumarthy2, C Liu6, J Sauter7, H Rizvi8, K C Arbour8, B W Carter9, J V Heymach10, M Altan10, M D Hellmann11, M M Awad12. 1. Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, USA. 2. Department of Medicine, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, USA. 3. Department of Data Sciences, Dana-Farber Cancer Institute, Boston, USA. 4. Departments of Radiology, Brigham and Women's Hospital, Boston, USA. 5. Departments of Pathology, Brigham and Women's Hospital, Boston, USA. 6. Departments of Radiology, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, USA. 7. Departments of Pathology, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, USA. 8. Departments of Medicine, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, USA. 9. Departments of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, USA. 10. Departments of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 11. Departments of Medicine, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, USA. 12. Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, USA. Electronic address: mark_awad@dfci.harvard.edu.
Abstract
BACKGROUND: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. PATIENTS AND METHODS: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . RESULTS: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. CONCLUSION: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.
BACKGROUND: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. PATIENTS AND METHODS: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . RESULTS: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. CONCLUSION: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.
Authors: Diego L Kaen; Nicolas Minatta; Alessandro Russo; Umberto Malapelle; Diego de Miguel-Pérez; Christian Rolfo Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675
Authors: Boris Duchemann; Jordi Remon; Marie Naigeon; Lydie Cassard; Jean Mehdi Jouniaux; Lisa Boselli; Jonathan Grivel; Edouard Auclin; Aude Desnoyer; Benjamin Besse; Nathalie Chaput Journal: Transl Lung Cancer Res Date: 2021-06