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



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).



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.



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%.



KEYNOTE-001 (ClinicalTrials.gov, NCT01295827).
Medical Oncology, Westmead Hospital and the University of Sydney, Sydney, Australia.
R
R
Hui
Hematology/Oncology, David Geffen School of Medicine at UCLA, Santa Monica, USA.
E B
EB
Garon
Hematology/Oncology, David Geffen School of Medicine at UCLA, Santa Monica, USA.
J W
JW
Goldman
Department of Medicine, Princess Margaret Cancer Centre, Toronto, Canada.
N B
NB
Leighl
Hematology/Oncology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
M D
MD
Hellmann
Oncology and Hematology Clinical Research, South Texas Accelerated Research Therapeutics, San Antonio, TX, USA.
A
A
Patnaik
Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
L
L
Gandhi
Medical Oncology, Yale University, New Haven, CT, USA.
J P
JP
Eder
Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
M-J
MJ
Ahn
Thoracic Oncology, Vanderbilt Ingram Cancer Center, Nashville, TN, USA.
L
L
Horn
Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
E
E
Felip
Medical Oncology, Catalan Institute of Oncology Badalona, Badalona, Spain.
E
E
Carcereny
Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA.
R
R
Rangwala
Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA.
G M
GM
Lubiniecki
Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA.
J
J
Zhang
Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA.
K
K
Emancipator
Companion Diagnostics, Dako, an Agilent Technologies Company, Carpinteria, CA, USA.
C
C
Roach
Thoracic Oncology, Columbia University, New York, USA.
N A
NA
Rizvi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C582435:pembrolizumab
anti-PD-1; immunotherapy; non-small cell lung cancer; pembrolizumab