Martin Reck, MD, PhD
Two-year results from the phase III KEYNOTE-024 trial showed that frontline pembrolizumab (Keytruda) more than doubled median overall survival (OS) compared with standard chemotherapy in patients with high PD-L1 expressing non–small cell lung cancer (NSCLC).
The median OS with the PD-1 inhibitor was 30.2 months versus 14.2 months with chemotherapy, representing a 37% reduction in the risk of death (hazard ratio, 0.63; 95% CI, 0.47-0.86; P
= .002). The findings, based on an additional 6 months of analysis from previous reporting, were presented at the 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan.1
“As we continue to see updated findings from this study of patients with non–small cell lung cancer in the first-line setting, practitioners are gaining valuable insights into the longer-term clinical benefit of Keytruda,” study author Martin Reck, MD, PhD, head of the department of thoracic oncology, LungenClinic Grosshansdorf, Germany, said in a press release. “The significant overall survival findings observed in KEYNOTE-024, which includes patients who have a poor prognosis, reinforce the use of Keytruda in appropriate patients in the first-line treatment of this disease.”
In the open-label trial, treatment-naive patients with advanced NSCLC were randomly assigned to pembrolizumab monotherapy (n = 154) or standard of care platinum-based chemotherapy (n = 151). therapy. Eligible patients had not undergone systemic chemotherapy treatment for their advanced disease, had tumors without an EGFR
sensitizing mutation or ALK
translocation, and had tumors expressing high levels of PD-L1 expression, defined as a tumor proportion score ≥50%, as determined by a central laboratory FDA-approved test.
Pembrolizumab was administered as a 200 mg IV infusion on the first day of each 21-day cycle until a maximum of 35 cycles or progressive disease. Patients assigned to chemotherapy received paclitaxel plus carboplatin, pemetrexed plus carboplatin, pemetrexed plus cisplatin, gemcitabine plus carboplatin, or gemcitabine plus cisplatin. Patients with nonsquamous NSCLC were allowed to take maintenance pemetrexed. The primary endpoint was PFS, with secondary outcome measures including OS and overall response rate (ORR).
Data presented at WCLC are based on a median follow-up of 25.2 months and included findings from 82 patients who crossed over from the chemotherapy group to receive pembrolizumab and 12 patients who received anti–PD-1 therapy outside of study crossover.
The 24-month OS rate was 51.5% versus 34.5% favoring the pembrolizumab arm. At 12 months, the OS rate was 70.3% in the pembrolizumab arm compared with 54.8% in the chemotherapy group.
The ORR was 45.5% (95% CI, 37.4-53.7) with pembrolizumab compared with 29.8% (95% CI, 22.6-37.8) in the chemotherapy group. Median duration of response was not reached in the pembrolizumab group (range, 1.8+ to 20.6+ months) compared with 7.1 months (range, 2.1+ to 18.1+ months) in the chemotherapy group.
Safety results were consistent with outcomes in previous trials among patients with metastatic NSCLC. In the pembrolizumab group, 31.2% of patients experienced grade ≥3 treatment-related adverse events (TRAEs).
The most common TRAEs were diarrhea, fatigue, pyrexia, pruritus, nausea, decreased appetite and rash. The most common immune-mediated adverse events in patients assigned to pembrolizumab were hypothyroidism, pneumonitis, hyperthyroidism, severe skin toxicity, and infusion reactions. There was 1 treatment-related death in the pembrolizumab group.
In results published in 2016, grade ≥3 TRAEs were twice as common among patients in the chemotherapy group as in the pembrolizumab group (53.3% vs. 26.6%).2
Incidence of serious TRAEs was similar between the two groups group (21.4% for pembrolizumab versus 20.7% for chemotherapy).
In the pembrolizumab group, 7.1% of patients discontinued treatment because of TRAEs compared with 10.7% of patients in the chemotherapy group. One patient in the pembrolizumab group died as a result of TRAEs, a sudden death of unknown cause on day 2. Three patients in the chemotherapy group died as a result of TRAEs, 1 due to pulmonary sepsis on day 25, 1 due to pulmonary alveolar hemorrhage on day 112, and 1 due to unknown cause on day 8).
Based on the initial findings from KEYNOTE-024, the FDA approved pembrolizumab in October 2016 for the frontline treatment of patients with metastatic NSCLC whose tumors have ≥50% PD-L1 expression based on an FDA-approved test and who do not harbor EGFR
- Brahmer JR, Rodríguez-Abreu D, Robinson AG, et al. Updated analysis of KEYNOTE-024: pembrolizumab vs platinum-based chemotherapy for advanced NSCLC with PD-L1 TPS ≥50%. Presented at: the IASLC 18th World Conference on Lung Cancer; October 15-18; Yokohama, Japan. Abstract OA 17.06 (ID 9582).
- Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833.