Does durvalumab with or without tremelimumab offer potential as a third line or later treatment of advanced non-small-cell lung cancer?

This study assessed whether patients with metastatic non-small-cell lung cancer (mNSCLC) would benefit from treatment using durvalumab (Imfinzi) with or without tremelimumab (CP-675,206) as a later treatment. The authors concluded that durvalumab showed improvement in overall survival (OS) and progression-free survival (PFS) in these patients. 

Patients with mNSCLC often experience disease progression (DP) following first- and second-line treatment. mNSCLC remains a difficult to treat cancer. It accounts for around 85% of all lung cancers. Pre-treated patients traditionally have a poor prognosis. More treatment options are required for these patients. Durvalumab plus tremelimumab are being assessed as treatment options for these patients. 

Durvalumab is an immunotherapy. Some cancers have on their surface a protein called PD-L1. This protein blocks the immune system function so the cancer can grow undetected. Durvalumab blocks the PD-L1 protein, therefore the immune system can detect and attack the cancer. Tremelimumab is also an immunotherapy that binds to a protein receptor called CTLA-4. It works in a similar way as durvalumab, on the immune system.

The safety and effectiveness of durvalumab with or without tremelimumab in patients with mNSCLC that have been heavily treated previously are still under investigation.

This study consisted of two independent studies. Study A consisted of 126 patients with mNSCLC and 25% of more cancer cells expressing the protein PD-L1 on their surface. These patients received either durvalumab or standard of care (SoC; standard medication for mNSCLC that their doctor chose – control group). Study B consisted of 469 patients with mNSCLC and fewer than 25% of cancer cells expressing the PD-L1 protein. These patients received durvalumab plus tremelimumab, or SoC (control group). 

In study A, the durvalumab group had an average overall survival (OS) of 11.7 months when compared to 6.8 months in the SoC group. The progression-free survival (PFS) for the durvalumab group was 3.8 months compared to 2.2 months in the SoC group. After 1 year, 49.3% of patients treated with durvalumab and 31.3% of those treated with SoC were alive.

In study B, the average OS of patients treated with durvalumab and tremelimumab was 11.5 months compared to 8.7 months with SoC. However, PFS was 3.5 months for both groups. 

In study A, 96.8% of the durvalumab group and 100% of the control group experienced side effects. Serious side effects were reported in 44.4% for the SoC group and 9.7% for the durvalumab group. In study B, treatment-related side effects were present in 36.4% in the SoC group and 22% in the durvalumab and tremelimumab group.

The authors concluded that in patients who had received several lines of treatment for progressive mNSCLC, the use of durvalumab with or without tremelimumab showed improved survival and was well tolerated.

This work was supported by AstraZeneca, the manufacturer of durvalumab and tremelimumab. Tremelimumab is currently undergoing clinical trials for the treatment of melanoma, mNSCLC, and mesothelioma.