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Ann Oncol. 2017 Apr 1;28(4):874-881. doi: 10.1093/annonc/mdx008.

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

Author information

1
Medical Oncology, Westmead Hospital and the University of Sydney, Sydney, Australia.
2
Hematology/Oncology, David Geffen School of Medicine at UCLA, Santa Monica, USA.
3
Department of Medicine, Princess Margaret Cancer Centre, Toronto, Canada.
4
Hematology/Oncology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
5
Oncology and Hematology Clinical Research, South Texas Accelerated Research Therapeutics, San Antonio, TX, USA.
6
Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
7
Medical Oncology, Yale University, New Haven, CT, USA.
8
Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
9
Thoracic Oncology, Vanderbilt Ingram Cancer Center, Nashville, TN, USA.
10
Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
11
Medical Oncology, Catalan Institute of Oncology Badalona, Badalona, Spain.
12
Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA.
13
Companion Diagnostics, Dako, an Agilent Technologies Company, Carpinteria, CA, USA.
14
Thoracic Oncology, Columbia University, New York, USA.

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 long-term 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).

KEYWORDS:

anti-PD-1; immunotherapy; non-small cell lung cancer; pembrolizumab

PMID:
28168303
PMCID:
PMC6354672
DOI:
10.1093/annonc/mdx008
[Indexed for MEDLINE]
Free PMC Article

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