From the Guidelines
The KEYNOTE A18 trial results are not directly available in the provided evidence, however, based on the available data from KEYNOTE-427 (Cohort B), pembrolizumab monotherapy demonstrated promising antitumor activity in patients with advanced non-clear cell renal cell carcinoma (anccRCC), particularly in those with papillary or unclassified histology, with an overall response rate (ORR) of 24.8% and a median follow-up of 11.1 months 1.
Trial Overview
The KEYNOTE-427 (Cohort B) trial evaluated the efficacy and safety of pembrolizumab monotherapy in patients with anccRCC.
- A total of 165 treatment-naive patients with anccRCC received pembrolizumab at 200 mg IV Q3W for 35 cycles, lasting about two years or until PD, unacceptable toxicity, or withdrawal.
- Confirmed histologies included: papillary 72% (n = 118), chromophobe 13% (n = 21), unclassified 16% (n = 26).
Efficacy and Safety
- At a median follow-up of 11.1 months, 56% of patients discontinued anti-PD-1 therapy due to PD or clinical progression.
- ORR was 24.8% (95% CI, 18.5–32.2), with 8 [4.8%] CRs and 33 [20%] PRs.
- Grade 3–5 TRAEs occurred in 11% of patients, while 6% discontinued due to TRAEs.
- Two patients died from TRAEs including pneumonia and cardiac arrest.
Patient Subgroups
- ORR (95% CI) was 25.4% (17.9–34.3) in patients with papillary histology tumors, 9.5% (1.2–30.4) in those with chromophobe tumors, and 34.6% (17.2–55.7) in those with unclassified nccRCC.
- ORR (95% CI) was 28.3% (16.8–42.3) for patients with favorable and 23.2% (15.8–32.1) with intermediate/poor IMDC risk and 33.3% (24.3–43.4) and 10.3% (3.9–21.2) for patients with tumor CPS ≥ 1 and CPS < 1 expression, respectively. It is essential to note that the provided evidence does not directly mention the KEYNOTE A18 trial, but the results from KEYNOTE-427 (Cohort B) can be used to inform treatment decisions for patients with anccRCC, as seen in 1.
From the Research
Results of the KEYNOTE (Pembrolizumab) A18 Trial
There are no research papers provided to directly answer the question about the results of the KEYNOTE (Pembrolizumab) A18 trial. However, the provided studies discuss the results of other KEYNOTE trials:
- KEYNOTE-042: 2
- First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater.
- The median survival values by TPS population were 20.0 months for pembrolizumab versus 12.2 months for chemotherapy.
- KEYNOTE-024: 3
- Pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy in patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells.
- The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group.
- KEYNOTE-001: 4, 5
- Pembrolizumab provides promising long-term OS benefit with a manageable safety profile for PD-L1-expressing treatment-naive advanced NSCLC, with greatest efficacy observed in patients with TPS ≥50%.
- At 36 months, investigator-assessed objective response according to immune-related response criteria was achieved for 41 of 101 treatment naive patients (41% [95% CI 30·9-50·8]; median duration of response was 16·7 months [95% CI 12·6-not reached]).
Some key points from the studies include:
- Pembrolizumab has shown antitumour activity and is a first-line and second-line treatment option for patients with programmed death ligand 1 (PD-L1)-expressing advanced non-small-cell lung cancer.
- Pembrolizumab provides durable response and long-term effects on overall survival, with tolerable safety, for treatment naive and previously treated patients with advanced non-small-cell lung cancer expressing PD-L1.
- PD-L1 tumour proportion score ≥50% was associated with longer median overall survival versus tumour proportion score 1-49%.