The recent phase II KEYNOTE-427 study investigated the efficacy and safety of pembrolizumab in patients with untreated advanced clear cell renal cell carcinoma (RCC) and non-clear cell RCC. Pembrolizumab is a type of immunotherapy (an immune checkpoint inhibitor called a programmed death 1 inhibitor, PD-1), which has been shown to be effective in untreated patients with various cancer types.
In this open-label phase II study, 110 patients with advanced, untreated clear cell RCC and 165 patient with advanced, untreated non-clear cell RCC were given pembrolizumab every 3 weeks for up to 24 months. The primary end point was cancer shrinkage (response rate).
For patients with clear cell RCC, response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% and most patients (68.2%) had cancer shrinkage, with almost a third with more than 60% shrinkage. Median duration of response was nearly 19 months and 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Colitis and diarrhoea were the most frequently reported side effects.
For patients with non-clear cell RCC, 71.5% had papillary, 12.7% had chromophobe, and 15.8% had unclassified RCC. Two-thirds of patients had intermediate or poor risk disease. Response rate to treatment was 26.7% and the median duration of response was 29 months; nearly 60% of responses lasted longer than 12 months. Response rate was 28.8% for papillary, 9.5% for chromophobe, and 30.8% for unclassified RCC. Overall, the median progression-free survival was 4.2 months and median overall survival was 28.9 months. Overall, nearly 70% of patients reported treatment-related side effects, most commonly itchy skin (pruritus, 20.0%) and low thyroid activity (hypothyroidism, 14.5%). Two deaths were treatment related (lung inflammation (pneumonitis) and cardiac arrest).
This study showed that pembrolizumab is promising as a first-line treatment for patients with advanced clear cell and non-clear cell RCC. Safety and tolerability of pembrolizumab was comparable to what has been previously reported for other tumour types.