What is the role of immunotherapy in small cell lung cancer (SCLC)?

From the Guidelines

Immunotherapy, specifically atezolizumab or durvalumab, in combination with platinum-based chemotherapy, should be offered as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) due to its proven benefit in improving overall survival. This recommendation is based on high-quality evidence from recent studies, including the 2023 guideline by the American Society of Clinical Oncology (ASCO) and Ontario Health (Cancer Care Ontario) 1. The standard regimen involves four cycles of combination therapy followed by maintenance immunotherapy until disease progression or unacceptable toxicity. For atezolizumab, the typical dose is 1200 mg IV every 3 weeks, while durvalumab is given at 1500 mg every 3 weeks.

Key points to consider when using immunotherapy in ES-SCLC include:

• The combination of immunotherapy with chemotherapy has been shown to improve overall survival by 2-3 months compared to chemotherapy alone 1
• Patients should be monitored for immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions
• Patients with autoimmune disorders or history of organ transplantation require careful consideration before initiating immunotherapy due to potential exacerbation of underlying conditions
• The role of PD-L1 or tumor mutational burden (TMB) as predictive biomarkers for immunotherapy efficacy in SCLC is still unclear, as studies have not shown a significant correlation 1

In terms of specific treatment regimens, the choice between atezolizumab and durvalumab should be based on individual patient factors and clinical judgment. Both agents have been shown to be effective in improving overall survival in ES-SCLC, and the decision to use one over the other should be made on a case-by-case basis. Overall, the use of immunotherapy in combination with chemotherapy has revolutionized the treatment of ES-SCLC, and its incorporation into clinical practice has the potential to improve outcomes for patients with this disease.

From the FDA Drug Label

TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: Small Cell Lung Cancer (SCLC) in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). (1.2)

Immunotherapy in small cell lung cancer is indicated with atezolizumab (TECENTRIQ) in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) 2.

• The recommended dosage is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.
• TECENTRIQ should be administered prior to chemotherapy when given on the same day.

From the Research

Immunotherapy in Small Cell Lung Cancer

• Immunotherapy has shown promise in the treatment of extensive-stage small-cell lung cancer, with studies demonstrating improved overall survival and progression-free survival when combined with chemotherapy 3, 4.
• The addition of immune checkpoint inhibitors, such as atezolizumab, to standard platinum-based chemotherapy has been shown to have a synergistic effect and improve efficacy in the treatment of small cell lung cancer 3, 5.
• However, despite these advances, the majority of patients do not respond to immunotherapy or relapse rapidly, highlighting the need for better understanding of the biology and molecular pathways of small cell lung cancer 5, 6.

Clinical Trials and Studies

• A phase 3 trial evaluating the efficacy and safety of atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer demonstrated significantly longer overall survival and progression-free survival compared to chemotherapy alone 3.
• A narrative review of immunotherapy in small cell lung cancer highlighted the need for further research to identify optimal predictive biomarkers and develop individualized therapeutic strategies 5.
• A single-center experience evaluating the efficacy and safety of atezolizumab in combination with etoposide and carboplatin in the first-line treatment of extensive-stage small-cell lung cancer demonstrated improved clinical outcomes and manageable safety profiles 7.

Future Perspectives

• Further efforts are required to better understand the role of immunotherapy in the treatment of small cell lung cancer and to identify patients most likely to benefit from this treatment strategy 4.
• Opportunities for further improvement of therapies include the addition of radiotherapy, co-stimulatory antibodies, and other immune-modifying agents 5, 6.
• The development of new treatment strategies, such as repurposing drugs, optimizing targets, and combination therapy strategies, may also enhance therapeutic effects and decrease adverse event rates in small cell lung cancer patients 6.