From the Guidelines
The KEYNOTE-A18 trial results are not directly mentioned in the provided evidence, however, based on the available data from other KEYNOTE trials, pembrolizumab has shown significant efficacy in improving outcomes for patients with non-small cell lung cancer (NSCLC). The evidence from the KEYNOTE-024 study 1 demonstrates that pembrolizumab monotherapy significantly improved median progression-free survival (PFS) and overall survival (OS) versus platinum-based chemotherapy in treatment-naive patients with metastatic NSCLC and high tumor programmed death ligand 1 (PD-L1) expression. Some key points to consider include:
- Pembrolizumab’s approval was based on results from the phase III KEYNOTE-024 study, which showed a significant improvement in median PFS and OS compared to platinum-based chemotherapy 1.
- The KEYNOTE-001 study also demonstrated a response rate of 41% in patients with advanced NSCLC and PD-L1 expression in at least 50% of tumor cells 2.
- The KEYNOTE-010 study showed that pembrolizumab at either 2 mg/kg or 10 mg/kg demonstrated longer OS compared with docetaxel in patients with advanced NSCLC expressing PD-L1 2, 3. It is essential to note that the provided evidence does not directly discuss the KEYNOTE-A18 trial, but the available data from other KEYNOTE trials suggest that pembrolizumab is an effective treatment option for patients with NSCLC, particularly those with high PD-L1 expression. Therefore, pembrolizumab can be considered a viable treatment option for patients with NSCLC, especially those with high PD-L1 expression, based on the evidence from other KEYNOTE trials 1, 2, 3.
From the FDA Drug Label
The trial demonstrated a statistically significant improvement in PFS in the overall population In an exploratory subgroup analysis for the 462 patients (44%) with FIGO 2014 Stage IB2-IIB disease, the PFS HR estimate was 0.91 (95% CI: 0.63, 1. 31), indicating that the PFS improvement in the overall population was primarily attributed to the results seen in the subgroup of patients with FIGO 2014 Stage III-IVA disease. Table 87: Efficacy Results in KEYNOTE-A18 (Patients with FIGO 2014 Stage III-IVA Cervical Cancer) EndpointKEYTRUDA200 mg every 3 weeks and400 mg every 6 weekswith CRTn=293Placebo with CRTn=303 PFS by Investigator Number of patients with event (%)61 (21%)94 (31%) Median in months (95% CI)NR (NR, NR)NR (18.8, NR) 12-month PFS rate (95% CI)81% (75, 85)70% (64, 76) Hazard ratio* (95% CI)0.59 (0.43, 0. 82)
The results of the KEYNOTE-A18 trial regarding Pembrolizumab efficacy are:
- A statistically significant improvement in PFS was demonstrated in the overall population.
- In patients with FIGO 2014 Stage III-IVA disease, the 12-month PFS rate was 81% for the Pembrolizumab arm and 70% for the placebo arm.
- The hazard ratio for PFS was 0.59 (95% CI: 0.43, 0.82), indicating a significant reduction in the risk of progression or death in the Pembrolizumab arm compared to the placebo arm 4.
From the Research
KEYNOTE-A18 Trial Results
The KEYNOTE-A18 trial is not directly mentioned in the provided evidence. However, the KEYNOTE-024, KEYNOTE-042, and KEYNOTE-091 trials are mentioned, which are related to pembrolizumab efficacy in non-small cell lung cancer (NSCLC) treatment.
Pembrolizumab Efficacy in NSCLC
- Pembrolizumab has shown improved overall survival (OS) and progression-free survival (PFS) in patients with advanced NSCLC with PD-L1 expression on at least 50% of tumor cells compared to platinum-based chemotherapy 5, 6.
- In the KEYNOTE-042 trial, pembrolizumab monotherapy improved OS in patients with a PD-L1 tumor proportion score (TPS) of 1% or greater, with a median OS of 16.7 months compared to 12.1 months with chemotherapy 6.
- The KEYNOTE-091 trial demonstrated that pembrolizumab significantly improved disease-free survival compared to placebo in completely resected stage IB-IIIA NSCLC, with a median disease-free survival of 53.6 months versus 42.0 months with placebo 7.
Pembrolizumab in Small Cell Lung Cancer (SCLC)
- A phase II study of maintenance pembrolizumab in patients with extensive-stage SCLC showed a median PFS of 1.4 months and a median OS of 9.6 months, with a 1-year OS rate of 37% 8.
- The study suggested that a subset of patients with SCLC may benefit from pembrolizumab, particularly those with PD-L1 expression in the tumor cells or stroma.
Note: The KEYNOTE-A18 trial is not mentioned in the provided evidence, and the results of the other KEYNOTE trials may not be directly applicable to the KEYNOTE-A18 trial.