Dataset Information

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 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).

SUBMITTER: Hui R

PROVIDER: S-EPMC6354672 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Hui R R Garon E B EB Goldman J W JW Leighl N B NB Hellmann M D MD Patnaik A A Gandhi L L Eder J P JP Ahn M-J MJ Horn L L Felip E E Carcereny E E Rangwala R R Lubiniecki G M GM Zhang J J Emancipator K K Roach C C Rizvi N A NA

Annals of oncology : official journal of the European Society for Medical Oncology 20170401 4

<h4>Background</h4>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.<h4>Patients and methods</h4>In the open-label phase 1b KEYNOTE-001 trial, treatment-naive ...[more]

PMID: 28168303

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Dataset Information

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

Background

Patients and methods

Results

Conclusions

Clinical trial name and number

Publications

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

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