Durvalumab as third-line treatment in advanced lung cancer – does gene expression affect response?

This study investigated if durvalumab (Infinzi) is effective in advanced non-small cell lung cancer (NSCLC) that has progressed on previous therapies. 

They found that the response to durvalumab was greatest in patients with high PD-L1 expression.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. In many cases, NSCLC is diagnosed at an advanced stage. Chemotherapy is the first-line therapy for NSCLC. In many cases, it is not successful. New drugs are in development to treat advanced cancer. Immune checkpoint inhibitors (ICIs) are one of these new treatment options. Durvalumab (DVB) is an ICI. It binds to a protein called PD-L1. By blocking PD-L1, the immune system can better detect and kill cancer cells. 

Some studies suggest that patients respond better to ICIs if the tumor cells have a high expression of PD-L1. Some NSCLC tumors also express mutated proteins that cause cancer cells to grow quickly. These include mutations (abnormalities) in the EGFR and ALK genes. It is unclear if EGFR/ALK-positive NSCLC can also benefit from DVB treatment. Also, it is not clear if patients who have had cancer progression after 2 or more therapies can benefit from DVB.

This study included 444 patients with advanced NSCLC. All patients had disease progression after at least 2 previous treatments. Patients were separated into 3 groups depending on tumor protein expression. One group had patients with EGFR/ALK-positive patients. A second group had EGFR/ALK-negative patients. The third group had EGFR/ALK-negative tumors that were also at least 90% PD-L1 positive. Patients were treated with DVB. The trial lasted up to 12 months. 

Overall, the response to DVB was positive in all groups. The response to DVB treatment was greater in patients with high PD-L1 level (30.9% vs. 12.2- 16.4%). Disease control (DC) rates were higher in patients with EGFR/ALK- negative tumors vs. EGFR/ALK-positive. DC rates were also higher in patients with higher PD-L1 expression levels. Progression-free survival rates were higher in high PD-L1 expression versus low PD-L1 expression patients. 

The authors concluded that the response to DVB was greatest in patients with high PD-L1 expression.

This study included a relatively small number of patients in each group. More investigation is needed.