Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: A phase 1 trial Journal Article


Authors: Hui, R.; Garon, E. B.; Goldman, J. W.; Leighl, N. B.; Hellmann, M. D.; Patnaik, A.; Gandhi, L.; Eder, J. P.; Ahn, M. J.; Horn, L.; Felip, E.; Carcereny, E.; Rangwala, R.; Lubiniecki, G. M.; Zhang, J.; Emancipator, K.; Roach, C.; Rizvi, N. A.
Article Title: Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: A phase 1 trial
Abstract: Background: Pembrolizumab improved survival as first- and second-line therapy compared with chemotherapy in patients with highly programmed death ligand 1 (PD-L1) expressing advanced non-small cell lung cancer (NSCLC). We report the longterm safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy. Patients and methods: In the open-label phase 1b KEYNOTE-001 trial, treatment-naive patients with advanced NSCLC whose tumors expressed PD-L1 (≥1% staining, assessed using a prototype assay) were randomly assigned to intravenous pembrolizumab 2 or 10 mg/kg every 3 (Q3W) or 2 (Q2W) weeks. Response was assessed per central RECIST v1.1 every 9 weeks in all patients who received≥1 pembrolizumab dose. Using pre-treatment tumor tissue, a clinical assay quantified the percentage of tumor cells expressing PD-L1 as tumor proportion score (TPS). Results: Between 1 March 2013 and 18 September 2015, 101 patients received pembrolizumab 2 mg/kg Q3W (n=6), 10 mg/ kg Q3W (n=49), or 10 mg/kg Q2W (n=46). Of these, 27 (26.7%) had TPS≥50%, 52 (51.5%) had TPS 1%-49%, and 12 (11.9%) had TPS<1%. The objective response rate (ORR) was 27% (27/101, 95% CI 18-37) and median overall survival was 22.1 months (95% CI 17.1-27.2). In patients with PD-L1 TPS≥50%, ORR, 12-month PFS, and 12-month OS were higher [14/27 (51.9%; 95% CI 32%-71%), 54%, and 85%, respectively] than the overall population [27/101 (26.7%; 95% CI 18.4%-36.5%), 35%, 71%]. Pembrolizumab was well tolerated, with only 12 (11.9%) patients experiencing grade 3/4 treatment-related adverse events and no treatment-related deaths. Conclusions: Pembrolizumab provides promising long-term OS benefit with a manageable safety profile for PD-L1- expressing treatment-naive advanced NSCLC, with greatest efficacy observed in patients with TPS ≥ 50%. Clinical trial name and number: KEYNOTE-001 (ClinicalTrials.gov, NCT01295827). © The Author 2017.
Keywords: immunotherapy; non-small cell lung cancer; anti-pd-1; pembrolizumab
Journal Title: Annals of Oncology
Volume: 28
Issue: 4
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2017-01-01
Start Page: 874
End Page: 881
Language: English
DOI: 10.1093/annonc/mdx008
PUBMED: 28168303
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 2 June 2017 -- Source: Scopus
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MSK Authors
  1. Matthew David Hellmann
    168 Hellmann