Checkpoint Inhibitor + Chemotherapy for Treatment of Small Cell Lung Cancer
by Dr. C.H.Weaver M.D. 3/2019
The U.S. Food and Drug Administration (FDA) has approved Tecentriq® (atezolizumab), in combination with carboplatin and etoposide (chemotherapy), for the initial treatment of extensive-disease small cell lung cancer (ED-SCLC). The approval represents the first new initial treatment option approved for SCLC in more than 20 years. (1)
Lung cancer is the leading cause of cancer death globally resulting in more than 4,800 deaths worldwide every day. Lung cancer is broadly divided into two major types: non-small cell lung cancer (NSCLC) and SCLC which is less common accounting for approximately 15% of all lung cancer diagnosis. (2,3)
About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death-ligand 1), which is expressed on cancer cells and cancer-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, Tecentriq enables the activation of T cells, restoring their ability to effectively detect and attack cancer cells.
The FDA approval is based on results from the IMpower133 clinical trial which were initially presented at the 2018 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine in late 2018.
IMpower133 directly compared Tecentriq in combination with chemotherapy (carboplatin and etoposide) to chemotherapy alone in 403 patients with newly diagnosed ED-SCLC. Tecentriq in combination with chemotherapy helped people live longer compared to chemotherapy alone (12.3 vs 10.3 months)
Imfinzi (durvalamab) is another checkpoint inhibitor designed to bind with PD-L1. Similar results for Imfinizi were presented at the 2019 Lung Cancer meetings showing an approximate 3 month improvement, ultimately leading to FDA approval in March of 2020. (5,6,7)
The Tecentriq and chemotherapy combination appeared to be well tolerated. The most common side effects were feeling tired or weak nausea, hair loss, decreased appetite, and constipation.
- Horn L et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018; DOI: 10.1056/NEJMoa1809064.
- World Health Organization. GLOBOCAN 2018; Lung Cancer: Estimated cancer incidence, mortality and prevalence worldwide. [Internet]: Lung fact sheet. Accessed January 2019.
- Alvarado-Luna G and Morales-Espinosa D. Treatment for small cell lung cancer, where are we now?- a review. Transl Lung Cancer Res. 2016;5(1):26-38
- FDA approves Roche’s Tecentriq in combination with chemotherapy for the initial treatment of adults with extensive-stage small cell lung cancer
- Paz-Ares L, Chen Y, Reinmuth N, et al. Overall survival with durvalumab plus etoposide-platinum in first-line extensive-stage SCLC: results from the CASPIAN study. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract PL02.11.
- International Association for the Study of Lung Cancer. Durvalumab combined with chemotherapy improves overall survival in patients with extensive stage small-cell lung cancer; first-line treatment reduced mortality risk by 27 percent. Published September 9, 2019. Accessed September 9, 2019.
- Imfinzi approved in the US for extensive-stage small cell lung cancer