Here is a quick guide to the KEYNOTE trials of the PD-1 inhibitor pembrolizumab in the renal cell carcinoma (RCC) setting. We outline the data that has been published in journals or presented at conferences thus far, and summarize the current regulatory status of the agent.
All trials are sponsored by the drug manufacturer Merck Sharp & Dohme.
KEYNOTE-426: Published
Phase 3 | |
Patient population: Treatment-naïve recurrent or metastatic clear-cell RCC | Treatment groups: Pembrolizumab 200 mg every 3 weeks plus axitinib 5 mg twice a day; sunitinib 50 mg/day on a 4 weeks on, 2 weeks off schedule |
As reported in The New England Journal of Medicine, pembrolizumab plus axitinib was associated with a significant 47% reduction in the risk for death relative to sunitinib, while the risk for disease progression or death was a significant 31% lower with the combination.
Subgroup analyses from the trial, presented at the 2019 ASCO Annual Meeting, favored pembrolizumab–axitinib in patients with IMDC intermediate/poor-risk disease and those with sarcomatoid features.
A report from China, published in Clinical Drug Investigation, showed that the combination is unlikely to be cost-effective versus sunitinib, with a total cost per patient of US$ 178,725 (€ 162,256) for pembrolizumab–axitinib and US$ 87,693 (€ 79,612) for sunitinib, for an additional 2.461 life–years (1.650 quality-adjusted life–years) with the combination.
Related news stories:
• Pembrolizumab–axitinib boosts untreated advanced RCC survival
• KEYNOTE-426 subgroup analyses confirm pembrolizumab–axitinib efficacy
• FDA approves first-line pembrolizumab–axitinib for advanced RCC
• EMA adopts new indications for pembrolizumab, atezolizumab
KEYNOTE-427: Ongoing
Phase 2 | |
Patient population: Treatment-naïve recurrent or metastatic clear-cell or non-clear-cell RCC | Treatment: Pembrolizumab 200 mg every 3 weeks |
This study is investigating front-line treatment with up to 35 doses of pembrolizumab for advanced clear-cell or non-clear-cell RCC.
Results from the clear-cell cohort were reported at the 2018 ASCO Annual Meeting, and showed an objective response rate (ORR) of 38.2%, with the median duration of response unreached at data cutoff (median follow-up of 12.1 months).
The PD-1 inhibitor also showed promised in patients with non-clear-cell disease, with an ORR of 24.8% over a median follow-up of 11.1 months. The median duration of response was again unreached. These data were presented at the 2019 ASCO Genitourinary Cancers Symposium.
Related news story: Immunotherapy-based regimens show promise in non-clear-cell RCC
KEYNOTE-564: Ongoing
Phase 3 | |
Patient population: Clear-cell RCC with an intermediate to high recurrence risk after nephrectomy | Treatment groups: Pembrolizumab 200 mg every 3 weeks; placebo |
This trial aims to evaluate the efficacy and safety of pembrolizumab in the adjuvant setting. Participants are required to have undergone nephrectomy following a diagnosis of clear-cell RCC and have an intermediate to high risk for recurrence. They will receive up to 17 cycles of either adjuvant pembrolizumab or placebo, with a view to assess disease-free survival as the primary endpoint.
Summary of approvals |
| The pembrolizumab–axitinib combination was approved by the US FDA in April 2019 for RCC patients who have not received prior treatment for advanced disease. Related news story: FDA approves first-line pembrolizumab–axitinib for advanced RCC |
| The EMA has also given the nod – in July 2019 – to pembrolizumab plus axitinib for adult patients with a new diagnosis of advanced RCC. Related news story: EMA adopts new indications for pembrolizumab, atezolizumab |
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This independent article was supported by an educational grant from Pfizer and Merck KGaA