Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study
- PMID: 31154919
- PMCID: PMC6768611
- DOI: 10.1200/JCO.19.00934
Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study
Abstract
Purpose: Pembrolizumab monotherapy has demonstrated durable antitumor activity in advanced programmed death ligand 1 (PD-L1)-expressing non‒small-cell lung cancer (NSCLC). We report 5-year outcomes from the phase Ib KEYNOTE-001 study. These data provide the longest efficacy and safety follow-up for patients with NSCLC treated with pembrolizumab monotherapy.
Patients and methods: Eligible patients had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumor sample for PD-L1 evaluation by immunohistochemistry using the 22C3 antibody. Patients received intravenous pembrolizumab 2 mg/kg every 3 weeks or 10 mg/kg every 2 or 3 weeks. Investigators assessed response per immune-related response criteria. The primary efficacy end point was objective response rate. Overall survival (OS) and duration of response were secondary end points.
Results: We enrolled 101 treatment-naive and 449 previously treated patients. Median follow-up was 60.6 months (range, 51.8 to 77.9 months). At data cutoff-November 5, 2018-450 patients (82%) had died. Median OS was 22.3 months (95% CI, 17.1 to 32.3 months) in treatment-naive patients and 10.5 months (95% CI, 8.6 to 13.2 months) in previously treated patients. Estimated 5-year OS was 23.2% for treatment-naive patients and 15.5% for previously treated patients. In patients with a PD-L1 tumor proportion score of 50% or greater, 5-year OS was 29.6% and 25.0% in treatment-naive and previously treated patients, respectively. Compared with analysis at 3 years, only three new-onset treatment-related grade 3 adverse events occurred (hypertension, glucose intolerance, and hypersensitivity reaction, all resolved). No late-onset grade 4 or 5 treatment-related adverse events occurred.
Conclusion: Pembrolizumab monotherapy provided durable antitumor activity and high 5-year OS rates in patients with treatment-naive or previously treated advanced NSCLC. Of note, the 5-year OS rate exceeded 25% among patients with a PD-L1 tumor proportion score of 50% or greater. Pembrolizumab had a tolerable long-term safety profile with little evidence of late-onset or new toxicity.
Trial registration: ClinicalTrials.gov NCT01295827.
Figures
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Comment in
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Five-year overall survival of pembrolizumab in advanced non-small cell lung cancer: another step from care to cure?Ann Transl Med. 2019 Sep;7(Suppl 6):S212. doi: 10.21037/atm.2019.08.91. Ann Transl Med. 2019. PMID: 31656791 Free PMC article. No abstract available.
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Are we facing a cure in lung cancer?-KEYNOTE-001 insights.Ann Transl Med. 2019 Sep;7(Suppl 6):S215. doi: 10.21037/atm.2019.08.87. Ann Transl Med. 2019. PMID: 31656794 Free PMC article. No abstract available.
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Breakthrough 5-year survival with pembrolizumab in Keynote-001 study: horizon shifting in advanced non-small cell lung cancer with immune check point inhibition.Ann Transl Med. 2020 Apr;8(8):555. doi: 10.21037/atm.2020.01.87. Ann Transl Med. 2020. PMID: 32411778 Free PMC article. No abstract available.
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Long-term survivors with immunotherapy in advanced NSCLC: is 'cure' within reach?Transl Cancer Res. 2020 Feb;9(2):409-414. doi: 10.21037/tcr.2019.12.82. Transl Cancer Res. 2020. PMID: 35117384 Free PMC article. No abstract available.
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