Prognostic and predictive value of the lung immune prognostic index in patients with advanced small cell lung cancers treated with immune checkpoint inhibitors

Lead Investigator: Edouard Auclin, Assistance Publique des Hôpitaux de Paris
Title of Proposal Research: Prognostic and predictive value of the lung immune prognostic index in patients with advanced small cell lung cancers treated with immune checkpoint inhibitors
Vivli Data Request: 9735
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

In 2020, lung cancer was responsible for 1.8 millions death worldwide. Among, lung cancer subtypes, small cell neuroendocrine tumours (cancers which arises from neuroendocrine cells in the bronchial tissue) account for approximately 15% of the cases. These tumours are aggressive with a poor prognostic and a metastatic presentation (have spread to other areas of the body) in most cases. In the last decade, immunotherapy with immune checkpoint inhibitors have revolutionised the therapeutic landscape of small cell lung cancers.
Immunotherapy, such as with immune checkpoint inhibitors, works by helping the immune system recognise and attack cancer cells. T cells are one type of immune cell and they have proteins on them that can turn the immune response on or off. These are called checkpoint proteins. Some types of cancers produce high levels of checkpoint proteins, turning off the T cells. Immune checkpoint inhibitors work by blocking the checkpoint proteins that turn off the immune response and therefore allow the immune system to recognise and attack the cancer cells.

Among these drugs, atezolizumab and durvalumab are immune checkpoint inhibitor treatments that have obtained their approval following two randomised trials. Programmed death-ligand 1 (PD-L1) is a checkpoint protein blocked by these two therapies. In combination with platinum-based chemotherapy they have been shown to prolong overall survival in patients with non-treated advanced small cell lung cancers. However, median overall survival was hardly longer than 12 months in the durvalumab or atezolizumab plus chemotherapy arms. Little is known regarding prognostic factors (variables that can be used to estimate the chance of recovery or relapse) in this population and predictive factors (a measurement associated with response or lack of response to a particular therapy) of durvalumab response.

The lung immune prognostic index (LIPI) is a simple low-cost prognostic tool which reflects the patient’s immune inflammation state (i.e. how much their immune system is responding to the cancer) before they start immunotherapy treatment.. This score was created in advanced non small cell lung cancer and then validated in several tumour types. It measures the levels of certain molecules in the blood and patients are then separated into three prognostic groups (good, intermediate and poor) depending on levels found.

In this study we aim to assess the prognostic and predictive values of the LIPI in patients treated with immunotherapy and chemotherapy for small cell lung cancer during their first treatment. This research could help clinician to decide wheither the addition of immune checkpoint inhibitors will have a real efficacy in patients, and thus avoid to expose the patients in which no activity is forecast to potential side effects.

Requested Studies:

A Phase III, Randomized, Multicenter,Open-Label, Comparative Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for the First-Line Treatment in Patients With Extensive Disease Small-Cell Lung Cancer (SCLC) (CASPIAN)
Data Contributor: AstraZeneca
Study ID: NCT03043872
Sponsor ID: D419QC00001

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