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.

FIG 1.

Kaplan-Meier estimates of 5-year overall survival. (A) Treatment-naive patients. (B) Previously treated patients. (C) Treatment-naive patients by programmed death ligand 1 (PD-L1) tumor proportion score (TPS) status. (D) Previously treated patients by PD-L1 TPS status. NOTE. There were too few patients (n = 12) in the treatment-naive PD-L1 TPS < 1% group to evaluate overall survival (OS).

FIG 2.

Time to response and time to progression by immune-related response criteria (irRC) per investigator assessment. Bars indicate time to last follow-up or disease progression, whichever occurred earlier. Response per irRC per investigator assessment, rather than per RECIST version 1.1, is reported for this analysis because central assessment of response ceased in April 2016. If the investigator considered a patient to be experiencing clinical benefit with continued treatment after disease progression and the patient was clinically stable and tolerating pembrolizumab, he or she was permitted to continue on pembrolizumab with the approval of the study sponsor. (A) Treatment-naive patients. (B) Previously treated patients. (*) Four patients in the previously treated group and one patient in the treatment-naive group received 3 or more years of pembrolizumab therapy and experienced disease progression. Baseline characteristics for these patients are summarized in the Data Supplement. (§) One patient in the previously treated group (marked with a purple triangle) received a second course of pembrolizumab therapy. The patient experienced a partial response (PR) during the first course and continued therapy for 44.4 months. After progressive disease (PD) at 47.2 months, the patient initiated a second course of pembrolizumab at 48.0 months and achieved a PR at 50.9 months. The patient received his last dose of pembrolizumab at 53.0 months and subsequently experienced PD at 53.7 months and died at 55.8 months. CR, complete response; PD-L1, programmed death ligand 1; TPS, tumor proportion score.

FIG 3.

Immune-mediated adverse events at 3 years (September 6, 2016) and at 5 years (November 5, 2018) of follow-up. Immune-mediated AEs were classified based on a list of preferred terms identified by the sponsor as having an immune etiology. Because there were changes in events included in this list between the 3- and 5-year analyses, certain events classified as immune-mediated at 3 years may not have been so-classified at 5 years.