What are the long-term effects of treatment with a biological drug versus chemotherapy for patients with advanced non-small cell lung carcinoma?

This study compared the long-term effects of biological drug pembrolizumab (Keytruda) with chemotherapy drug docetaxel (Taxotere) in patients with advanced non-small cell lung carcinoma (NSCLC). The study found that pembrolizumab increased survival and had fewer side effects than docetaxel.

Patients with advanced NSCLC require treatments that increase survival and prevent cancer progression. Many patients with NSCLC have increased amounts of a protein called PD-L1. This protein is used by the cancer to turn off the immune system in tumors. Pembrolizumab is a biological drug that blocks PD-L1 and allows the immune system to be switched on. 

Previous studies have shown that pembrolizumab has successfully improved treatment results for patients compared with chemotherapy. These results include patients with little PD-L1 amounts in their tumors.  However, it is unclear if these results continue over the long-term for patients.

1034 patients with advanced NSCLC were divided into two groups. The first group (691 patients) were given pembrolizumab. The second group (343 patients) were given docetaxel. Patients were followed for 35.2 to 53.2 months (average 42.6 months).

Pembrolizumab increased the survival of patients over docetaxel. Patients with a high amount of PD-L1 had a 47% higher chance of survival with pembrolizumab than docetaxel.  Patients with a low amount of PD-L1 had a 31% higher chance of survival with pembrolizumab. Patients with a high amount of PD-L1 survived for an average of 16.9 months with pembrolizumab compared to 8.2 months with docetaxel.  Patients with a low amount of PD-L1 survived for an average of 11.8 months with pembrolizumab and 8.4 months with docetaxel.

Pembrolizumab increased the chance of survival without cancer progression by 43% in patients with high PD-L1 and by 17% in patients with low PD-L1. After 36 months, 21.9% of patients with high PD-L1 did not have cancer progression with pembrolizumab treatment compared to 1.2% with docetaxel.  12.7% of patients with low PD-L1 did not have cancer progression after pembrolizumab compared to 1% with docetaxel.

The percentage of patients who developed side effects was 67.7% in the pembrolizumab group and 82.5% in the docetaxel group. Fatigue was the most common side effect, with 15.8% of the pembrolizumab group and 24.9% of the docetaxel experiencing it. 

The authors concluded that pembrolizumab is more effective and safer than docetaxel long-term for patients with advanced NSCLC regardless of the amount of PD-L1.

The manufacturer of pembrolizumab, Merck Sharpe and Dohme, funded this study.