The Phase 3 KEYNOTE-042 trial, evaluating pembrolizumab (Keytruda) for participants with programmed cell death-ligand 1 (PD-L1)-positive advanced or metastatic non-small cell lung cancer (NSCLC), reached primary completion on 2018-09-04. The study demonstrated that pembrolizumab significantly prolonged overall survival, with a median of 20.0 months compared to 12.2 months for platinum-based chemotherapy in participants with a tumor proportion score (TPS) of ≥50%.

Background

The trial investigated pembrolizumab for the treatment of participants with programmed cell death-ligand 1 (PD-L1)-positive advanced or metastatic non-small cell lung cancer (NSCLC). This condition is a significant area of unmet medical need.

Trial design

The Phase 3 KEYNOTE-042 trial (NCT02220894), titled "Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer," enrolled 1274 participants. The study focused on participants with non-small cell lung cancer who had PD-L1-positive tumors. Participants were randomized to receive either single-agent pembrolizumab for up to 35 treatments or standard of care platinum-based chemotherapy, which included carboplatin plus paclitaxel or carboplatin plus pemetrexed for 4 to 6 21-day cycles. The primary study hypothesis was that pembrolizumab prolongs overall survival compared to standard of care chemotherapy.

Key results

The trial reported key measurements and analyses for overall survival (OS) and progression-free survival (PFS) across different tumor proportion score (TPS) thresholds:

  • For participants with a TPS of ≥50%, median OS was 20.0 months for the pembrolizumab arm compared to 12.2 months for the chemotherapy arm. The hazard ratio (HR) for OS was 0.7 (95.0% CI: 0.58, 0.86; p=0.0003).
  • For participants with a TPS of ≥20%, median OS was 18.0 months for the pembrolizumab arm compared to 13.0 months for the chemotherapy arm. The HR for OS was 0.77 (95.0% CI: 0.65, 0.91; p=0.0012).
  • For participants with a TPS of ≥1%, median OS was 16.4 months for the pembrolizumab arm compared to 12.1 months for the chemotherapy arm. The HR for OS was 0.82 (95.0% CI: 0.71, 0.93; p=0.0013).
  • For participants with a TPS of ≥50%, median PFS was 6.5 months for the pembrolizumab arm compared to 6.4 months for the chemotherapy arm. The HR for PFS was 0.83 (95.0% CI: 0.69, 1.0; p=0.026).
  • For participants with a TPS of ≥20%, median PFS was 6.2 months for the pembrolizumab arm compared to 6.7 months for the chemotherapy arm. The HR for PFS was 0.94 (95.0% CI: 0.8, 1.1; p=0.2134).
  • For participants with a TPS of ≥1%, median PFS was 5.4 months for the pembrolizumab arm compared to 6.6 months for the chemotherapy arm. The HR for PFS was 1.05 (95.0% CI: 0.93, 1.19; p=0.7964).

What this means

The results from the KEYNOTE-042 trial indicate that pembrolizumab significantly improves overall survival compared to platinum-based chemotherapy in patients with PD-L1-positive advanced or metastatic NSCLC, particularly in those with higher PD-L1 expression (TPS ≥50%, ≥20%, and ≥1%). While the OS benefit was consistent across all PD-L1 expression levels, the most pronounced difference was observed in the highest expression group. The PFS data showed a more modest benefit, or even a slight disadvantage, for pembrolizumab compared to chemotherapy, especially in the broader TPS ≥1% and ≥20% populations, suggesting that OS is the primary driver of benefit in this setting.

Source

The primary completion status and results for the KEYNOTE-042 trial were posted on 2018-09-04 on ClinicalTrials.gov, an official database of clinical studies. The full details are available on clinicaltrials.gov under the identifier NCT02220894.