Studies Supporting the Use of PD-L1 Therapy Plus Chemo in ES-SCLC


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Federico Albrecht, MD, comments on clinical trials supporting the use of PD-L1 inhibitor therapy in combination with standard chemotherapy for the treatment of patients with extensive-stage small cell lung cancer.

Federico Albrecht, MD, an oncologist/hematologist at Miami Cancer Institute, discusses evidence-based treatment of extensive-stage small cell lung cancer (ES-SCLC).

Albrecht says that ES-SCLC is aggressive and progresses quickly. Therefore, after initial treatment patients with ES-SCLC experience disease recurrence. There were 2 important clinical trials that provide guidance on how to approach treatment of these patients.

First, adding PD-L1 to standard chemotherapy was shown to improve survival in patients with ES-SCLC in the IMpower133 study (NCT02763579), which evaluated the use of atezolizumab (Tecentriq) in combination with the chemotherapy doublet, carboplatin plus etoposide. Initial findings published in the New England Journal of Medicine showed a median overall survival (OS) of 12.3 months with the addition of atezolizumab vs 10.3 months with chemotherapy alone. The median progression-free survival shown was 5.2 months with atezolizumab and chemotherapy compared with 4.3 months with chemotherapy alone. Updated findings published in the Journal of Clinical Oncology confirmed that chemotherapy plus atezolizumab is a standard of care.

In another study, CASPIAN (NCT03043872), the addition of durvalumab (Imfinzi) to platinum-etoposide or of tremelimumab (Imjudo) to platinum-etoposide led to significant improvements in OS in patients with ES-SCLC. Primary results showed a median OS of 13.0 months with added durvalumab vs 10.3 months with platinum-etoposide alone. Three-year OS analysis results from CASPIAN were presented at the European Society of Medical Oncology Congress in 2022, further demonstrating the durvalumab added to platinum-etoposide if a standard of care therapy for ES-SCLC.


0:09 | As you know, small cell lung cancer is an aggressive and rapidly progressing malignancy. So, while typically respond to initial chemotherapy, the orphans recur and in in a matter of months resulting in a poor prognosis. So, 2 crucial phase three trials have been conducted in recent years. The first one is called the IMpower133, which was initially published in the New England Journal of Medicine in2018 and subsequently updated and published in the Journal of Clinical Oncology. This study demonstrated that adding a PD-L1 monoclonal antibody to the standard treatment of carboplatin and etoposide improved survival. Furthermore, patients were able to continue receiving this immunotherapy as maintenance treatment until this is progression.

1:08 | The second study, known as the CASPIAN trial, [which] investigated the use of durvalumab and other PD-L1 monoclonal antibody, in combination with carboplatin or cisplatin and etoposide. It was first published in The Lancet into 2019, and it also received recent updates.

1:43 | So, once again, both trials showed an improvement in survival rates for the first time in more than 20 years. So, both of these agents have now been approved by the FDA and have become the standard of care for patients with extensive disease small cell lung cancer. Currently, research is underway to determine whether similar benefits can be achieved in patients with limited-stage disease small cell lung cancer.

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