Should durvalumab be considered a first-line treatment for extensive small cell lung cancer?

This study looked at the effectiveness of durvalumab (Imfinzi) with or without tremelimumab plus platinum-etoposide (Etopophos) (PE) versus PE-alone for the treatment of extensive-stage small-cell lung cancer (ESCLC). The authors found that durvalumab plus PE showed sustain survival improvement in these patients.

Small-cell lung cancer (SCLC) is responsible for 15% of all lung cancer diagnoses. First-line care for ES-SCLC remains chemotherapy with etoposide and/or platinum drugs such as carboplatin (Paraplatin). SCLC spreads quickly around the body. SCLC is usually responsive to chemotherapy, however, this response does not usually last. To improve responses, other therapies are needed.

Durvalumab is an immunotherapy. Some cancers have on their surface a protein called PD-L1. This protein blocks the immune system's 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. 

In the short term, durvalumab plus PE CT has shown to improve survival in patients with extensive-stage SCLC. However, longer-term data for this combination are missing. 

There were 805 patients with extensive-stage SCLC included in this trial. Patients were randomly assigned to one of 3 groups. 268 patients received durvalumab, tremelimumab, and PE (DTPE group). 268 patients received durvalumab plus PE (DPE group). 269 patients received PE alone (PE group). The average length of follow-up was 25.1 months. 

DTPE was not associated with an increase in overall survival (OS) when compared to PE alone treatment (10.4 months vs. 10.5 months). However, the DPE combination showed an improved OS of 12.9 months compared to PE alone (10.5 months). The addition of durvalumab to PE was associated with a 25% higher chance of survival compared to PE alone.

After 18 months, 32% of patients in the DPE group were alive compared to 24.8% in the PE group. 58% in the DTPE and PE group had a tumor response. Tumor response was higher in the DPE group (68%).

Side effects were experienced in all groups. The most common severe side effect experienced by all groups was low white blood cell counts (33% – DTPE, 24% – DPE group, and 33% – PE). 

The authors concluded that the addition of durvalumab to PE improved the survival of patients with extensive-stage SCLC and should be considered as a first-line treatment for these patients. 

This study was funded by AstraZeneca, the manufacturers of durvalumab and tremelimumab. The patients were aware of the medication they received. This may have influenced the results.