Which immunotherapy is the most effective for non-small cell lung cancer?

This article compared the safety and effectiveness of PD-L1/PD-1 immunotherapies (IT) for non-small cell lung cancer (NSCLC). The authors found that in the first-line setting, the most effective treatments for PD-L1 positive NSCLC were atezolizumab (Tecentriq), pembrolizumab (Keytruda)/chemotherapy (CT) combination, and nivolumab (Opdivo)/ipilimumab (Yervoy). 

NSCLC is a form of lung cancer. It is responsible for around 85% of all lung cancer diagnoses. Despite many existing treatment options, NSCLC can spread quickly and become resistant to treatments. Immunotherapies such as anti-PD-L1/PD-1 inhibitors have become an important treatment for these patients. 

PD-L1/PD-1 or programmed death cell protein is a protein found on certain cancer cells. This protein can stop certain cancer treatments from working by shutting down the immune system. Atezolizumab (Ate), pembrolizumab (Pem), and nivolumab (Niv) are anti-PD-1/PD-L1 drugs. They block this protein from working which can help turn the immune system back on to detect and kill cancer cells. Nivolumab is frequently combined with another immunotherapy, ipilimumab (Ipi). Despite existing trials showing the effectiveness of these drugs, the optimum treatment regimen for patients with NSCLC has not yet been found due to difficulty in comparing existing trials. 

The authors carried out an analysis of 19 articles with 12,753 patients with NSCLC. 9 treatment regimens were evaluated in these trials. These included Pem alone or combined with chemotherapy (CT), Ate alone or with CT, Niv alone, Niv+CT, Niv+Ipi, and durvalumab (Dur; Infinzi) alone. All these regimens were compared to CT. 

Patients who received Pem+CT had the best outcome in terms of overall survival. Pem+CT was associated with a 37% higher survival compared to CT alone. Niv+Ipi was associated with a 27% higher survival compared to CT alone. Pem alone was associated with a 26% higher survival compared to CT, followed by Ate which had a 23% higher chance of survival, and Niv alone and Niv+CT with a 19% higher chance of survival compared to CT. Dur did not have a significant benefit in overall survival compared to CT.

Pem+CT also had the most benefit in survival without cancer worsening compared to CT (48% increase).

In terms of severe side effects, Niv, Ate, Pem, and Dur, all had lower risks of side effects compared to CT.

In patients with 50% or more cancer cells positive for the PD-L1 protein, Ate had the most benefit in survival compared to CT (51% increase). In those with 1-49% cancer cells positive for the PD-L1 protein, Pem+CT combination was associated with a 40% increase in survival and Pem alone with a 15% increase in survival compared to CT alone. In patients with less than 1% cancer cells positive for the PD-L1 protein, Niv+Ipi combination had a 38% better chance of survival compared to CT alone. 

The authors found that the most effective treatments for PD-L1 positive NSCLC were atezolizumab, pembrolizumab+CT, and nivolumab/ipilimumab.

This study did not directly compare these therapies.