Does durvalumab (generic name) or atezolizumab (generic name) have a benefit in small cell lung cancer even if programmed death-ligand 1 (PD-L1) expression is low?

From the Guidelines

Durvalumab and atezolizumab have shown benefit in small cell lung cancer (SCLC) regardless of PD-L1 expression levels, including in patients with low PD-L1 expression. The most recent and highest quality study, a 2023 guideline published in the Journal of Clinical Oncology 1, recommends first-line systemic therapy with CE or PE plus immunotherapy (atezolizumab or durvalumab) followed by maintenance immunotherapy for patients with extensive-stage small-cell lung cancer (ES-SCLC). This recommendation is based on high-quality evidence and has a strong strength of recommendation.

Key Points

• The CASPIAN trial demonstrated improved overall survival when durvalumab was added to standard platinum-etoposide chemotherapy in extensive-stage SCLC, with benefits observed across all PD-L1 subgroups 1.
• The IMpower133 trial similarly showed survival benefits when combined with carboplatin-etoposide in extensive-stage SCLC, regardless of PD-L1 status 1.
• The recommended regimen for durvalumab is 1500 mg every 3 weeks with chemotherapy for 4 cycles, followed by maintenance durvalumab 1500 mg every 4 weeks until disease progression.
• The standard regimen for atezolizumab is 1200 mg every 3 weeks with chemotherapy for 4 cycles, followed by maintenance atezolizumab until progression.
• These immunotherapy agents work by blocking the PD-1/PD-L1 pathway, enhancing T-cell activity against cancer cells.

Benefits and Risks

• The addition of durvalumab or atezolizumab to chemotherapy has been shown to improve overall survival and progression-free survival in patients with ES-SCLC, regardless of PD-L1 expression levels 1.
• The toxicity profile of durvalumab and atezolizumab is generally manageable, with similar rates of grade 3-4 adverse events compared to chemotherapy alone 1.
• Immune-related adverse events are more common with durvalumab and atezolizumab, but are generally manageable with appropriate monitoring and treatment 1.

From the Research

Efficacy of Durvalumab and Atezolizumab in Small Cell Lung Cancer

• The efficacy of durvalumab and atezolizumab in small cell lung cancer, even with low PD-L1 expression, has been investigated in several studies 2, 3, 4.
• A retrospective study found that durvalumab was associated with improved overall survival in patients with extensive-stage small cell lung cancer, with a median overall survival of 14.7 months compared to 11.6 months with atezolizumab (HR 0.59; 95% CI, 0.38-0.92; P = 0.020) 2.
• Another study found that the median overall survival of patients who received atezolizumab or durvalumab was 10.0 and 17.1 months, respectively (p = 0.163), although this difference was not statistically significant 3.
• A retrospective comparative cohort study found that the median OS of patients who received durvalumab or atezolizumab as the first-line treatment were 22.0 and 10.0 months, respectively (P = 0.03) 4.

Safety of Durvalumab and Atezolizumab

• The safety of durvalumab and atezolizumab in small cell lung cancer has also been investigated in several studies 2, 3, 4.
• A study found that atezolizumab was associated with a numerically higher incidence of immune-related adverse events (47.8% versus 32.7%, P = 0.157) and hospitalization rates for those with an immune-related adverse event (36.4% versus 16.7%, P = 0.204) 2.
• Another study found that there was no significant difference in the incidence of immune-related adverse events between the two groups (P > 0.05) 3.
• A retrospective comparative cohort study found that there was no significant difference in the incidence of immune-related adverse events during PD-L1 inhibitor therapy between the two groups (P > 0.05) 4.

PD-L1 Expression

• The studies did not specifically investigate the efficacy of durvalumab and atezolizumab in small cell lung cancer with low PD-L1 expression 2, 3, 4.
• However, a study on non-small cell lung cancer found that atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type 5.
• The relevance of PD-L1 expression to the efficacy of durvalumab and atezolizumab in small cell lung cancer is not well established and requires further investigation.