Can pembrolizumab combined with chemotherapy slow the progression of extensive stage small-cell lung cancer?

The study evaluated the addition of pembrolizumab (Keytruda) to etoposide (Etopophos) and platinum chemotherapy drugs for patients with untreated extensive-stage (ES) small-cell lung cancer (SCLC). The study found that pembrolizumab improved progression-free survival (PFS; survival without cancer getting worse) when added to etoposide and platinum (EP) chemotherapy in these patients.

SCLC is an aggressive type of lung cancer that accounts for 15% of all lung cancers. SCLC is a difficult to treat cancer. It grows rapidly and spreads quickly around the body. SCLC is more responsive to chemotherapy than non-small cell lung cancer (NSCLC), however, responses usually do not last. First-line care for ES-SCLC remains chemotherapy with etoposide or platinum drugs such as carboplatin (Paraplatin). To improve responses, other therapies are needed.

Monoclonal antibodies (mAb) are y-shaped proteins that bind to one site on the surface of another cell. Pembrolizumab is a mAb. It binds to PD-L1 (a protein found in cancer cells that block the immune system). Therefore, pembrolizumab reactivates the immune system to kill cancer cells. Pembrolizumab alone has shown good responses used alone in patients with SCLC. However, it is not known if adding pembrolizumab to EP chemotherapy would be effective in these patients. 

There were 453 participants in this study. The patients had SCLC that had not been previously treated with systemic (whole-body) therapy. Patients were randomly assigned to a pembrolizumab plus EP chemotherapy (228) or a placebo plus EP (225) group. Tumor imaging was used to assess PFS. The average follow-up period was 21.6 months. 

The pembrolizumab plus EP group showed an improved PFS of 13.6% over 12-months. In comparison the placebo plus EP had a PFS of 3.1%. The addition of pembrolizumab significantly improved PFS by 25%. The overall survival rate at 12 months was slightly higher in the pembrolizumab group (45.1%) compared tot he placebo group (39.6%).

The overall response rate was 70.6% in the pembrolizumab group compared to 61.8% in the placebo group. The average time the response lasted was 4.2 months in the pembrolizumab group compared to 3.7 months in the placebo group.

14.3% of the pembrolizumab group and 6.3% of the placebo group stopped treatment because of side effects. The most common side effects in both groups were low levels of white and red blood cell counts, nausea, and hair loss.

The authors concluded that pembrolizumab plus EP improved PFS as treatment for patients with ES-SCLC

Pembrolizumab was approved as a third-line or later therapy for patients with metastatic SCLC in several countries, including the United States. This study was supported by Merck Sharp & Dohme Corp, the manufacturer of pembrolizumab.