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.

Read more in UroToday here for clear cell RCC

Read more in UroToday here for non-clear cell RCC