Could immunotherapy be more beneficial than chemotherapy at treating some types of NSCLC?

This trial determined whether pembrolizumab (Keytruda) is more effective at treating advanced NSCLC than chemotherapy in patients with high levels of a specific protein called PD-L1. The authors concluded that, for this subgroup of patients, pembrolizumab was more effective and safer than chemotherapy.

In some patients with NSCLC, tumor cells may express (produce) a protein called PD-L1. PD-L1 stops the activity of the immune system. There are now therapies which can target this directly and help activate the patients’ own immune cells against the cancer. Pembrolizumab is one example of this type of therapy. Pembrolizumab has been shown to be an effective treatment for advanced NSCLC with high PD-L1 expression. Currently, the first line treatment for most patients with NSCLC is chemotherapy. It remains unknown whether targeted immunotherapy would be more effective than chemotherapy at treating certain types of NSCLC.

The authors aimed to establish whether pembrolizumab was more effective than chemotherapy at treating advanced NSCLC with high PD-L1 expression.

305 patients who had not been previously treated were included. Of these, 154 patients were treated with pembrolizumab (group 1) and 151 were treated with chemotherapy. Following treatment, the patients were assessed for progression free survival (PFS; time from beginning trial to disease progression or death), overall survival (OS; time from beginning of trial to death) and objective response rate (percent of patients who responded to the treatment).

The average follow up was 11.2 months. The average PFS for group 1 was 10.3 months compared to 6 months for group 2 patients. Six-month OS was 80.2% in group 1 compared to 72.4% for group 2. Patients in group 1 were 40% more likely to have a longer overall survival. 44.8% of patients in group 1 saw a response to the treatment, compared to 27.8% in group 2.

73.4% of patients in group 1 and 90% of patients in group 2 had an adverse effect. 7% of patients in group 1 had to stop treatment due to side effects compared to 10.7% in group 2. The most common side effects in group 1 were diarrhea (14.3%), fatigue (10.4%) and fever (10.4%). The most common side effects in group 2 were nausea (43.3%), anemia (low red blood cell levels, 44%) and fatigue (28.7%). One patient in group 1 and three patients in group 2 died due to treatment related side effects.

The authors concluded that for patients with high levels of PD-L1 expression, pembrolizumab was more associated with improved PFS and OS compared to chemotherapy.

The study was funded by Merck, the manufacturers of pembrolizumab.