Lead Investigator: Xiaoling Shang, Shandong University
Title of Proposal Research: A clinical variable based-Nomogram could predict survival for Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide
Vivli Data Request: 8344
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Small cell lung cancer accounts for approximately 15% of all lung cancer. The prognosis of patients with small cell lung cancer is dismal with a 5-year survival rate of less than 5% and an average overall survival period of only 2–4 months for patients not receiving any active treatment. According to the Veterans Administration Lung Study Group (VALG) which is a lung cancer staging system that is used worldwide, small cell lung cancer is divided into limited and extensive stages. Patients with extensive stages mean that cancers have spread widely throughout the lung, to the other lung, to lymph nodes on the other side of the chest, or to other parts of the body (including the bone marrow). And nearly 2/3 of patients with small cell lung cancer have extensive stage at the time of diagnosis. Therapeutic options for small cell lung cancer are limited. Platinum chemotherapy means that platinum-based drugs have the metal element platinum as part of their molecular structure and work by causing damage to the DNA of cancer cells to prevent them from multiplying. Platinum chemotherapy (carboplatin or cisplatin) combined with etoposide has always been the standard treatment for small cell lung cancer with extensive stage. The median overall survival for extensive stage small cell lung cancer patients treated with standard frontline chemotherapy is only approximately 10 months.
Immunotherapy has demonstrated improved prognosis in patients with extensive-stage small cell lung cancer, especially the application of immune checkpoint inhibitors. Immune checkpoint inhibitors (ICIs) could prevent the cancer cells from “hiding” from the immune system and result in cancer cells being destroyed by the immune system. Additionally, ICIs could reduce the immunosuppression in the tumor microenvironment and reactivate the antitumor function of T cells (T cells are part of the immune system that destroy foreign particles, including cancer cells) through inhibiting the cytotoxic T lymphocyte-associated protein 4 and programmed cell death-1 and programmed cell death receptor ligand-1 pathway. Based on data from previous clinical studies, an initial phase II study evaluated the safety and efficacy of ipilimumab in combination with carboplatin and etoposide as first-line chemotherapy for patients with extensive stage small cell lung cancer. In this trial, 42 patients were enrolled, and 72.4% of patients achieved an objective response, while 84.8% achieved an immune-related objective response. KEYNOTE-028 was a phase Ib trial conducted to evaluate the safety and efficacy of pembrolizumab in 24 recurrent small cell lung cancer patients with PD-L1 positive tumors. And pembrolizumab demonstrated promising antitumor activity in patients with pretreated small cell lung cancer.
Nomograms are a pictorial representation of a complex mathematical formula. Medical nomograms use biologic and clinical variables, such as tumor grade and patient age, to graphically depict a statistical prognostic model that generates a probability of a clinical event, such as cancer recurrence or death. Nomogram prognostic models could greatly facilitate risk stratification and treatment planning, as well as more refined enrollment criteria for clinical trials. The nomograms could provide useful tools for clinicians and researchers to stratify the risk of small cell lung cancer patients. However, to date, no nomogram model has been constructed to predict survival for extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide.
A Phase I/III, Randomized, Double-Blind, Placebo-Controlled Study of Carboplatin Plus Etoposide With or Without Atezolizumab (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02763579
Sponsor ID: GO30081