Lead Investigator: Laura Mezquita, Hospital Clinic and the Translational Genomics Group at IDIBAPS
Title of Proposal Research: Prospective validation of the Lung Immune Prognostic Index in patients with non-small cell and small cell lung cancers.
Vivli Data Request: 7163
Funding Source: None
Potential Conflicts of Interest: For Dr. Mezquita: Research grant/Funding (self): Bristol Myers Squibb, Boehringer Ingelheim, Amgen, Stilla, Inivata; Advisory/Consultancy: Roche Diagnostics, Takeda; Honoraria (self): Bristol Myers Squibb, Tecnofarma, Roche; Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies: AstraZeneca.
The current research is not funded by the data contributor Roche.
For Dr. Auclin: Travel/Accommodation/Expenses: Mundipharma; Honoraria (self): Sanofi Genzymes. Consultant: Amgen, Sanofi
Summary of the Proposed Research:
Lung cancer is the first cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is a type of cancer that accounts for 85% of lung cancer. Its major risk factor is smoking. In patients with metastases, the main treatments combine chemotherapy and immunotherapy. lmmunotherapy involves boosting the immune system in order to unmask cancer cells and destroy them. Inflammation is a negative factor for immunotherapy efficacy. Inflammation is identified by several components in blood (i.e.) inflammatory biomarkers which can be measured in blood tests. Our team has created the Lung Immune Prognostic Index (LIPI) based on inflammatory biomarkers levels at the introduction of immunotherapy. The objective of this research is to apply the LIPI on a large population of patients included in prospective trials and to assess the potential value in the treatment choice for patients with lung cancer
Statistical Analysis Plan:
STUDIES SELECTION
We selected the trials according to the following criteria:
– patients with NSCLC and SCLC
– patients treated with ICI in monotherapy or in combination
– for the predictive analysis: randomized trials with ICI and non-ICI containing arms.
STATISTICAL ANALYSIS
A description of the population will be provided. Median values (interquartile range) and frequencies (percentage) were provided for description of continuous and categorical variables, respectively. Medians and proportions were compared using Student’s t test and chi-square test (or Fisher’s exact test, if appropriate), respectively.
The association of LIPI along with demographic, clinical, biological and molecular factors with survival will be first assessed by the univariate Cox-proportional-hazard model, providing hazard ratios (HRs) and 95% CIs. Parameters with P values of <0.10 in univariate analysis and/or clinically relevant variables will be entered into the multivariable Cox-regression model.
The predictive value of LIPI on ICI benefit will be explored with an interaction term in a the Cox-regression model and illustrated with Kaplan Meier curves.
Firstly, each study will be analyzed separately in order to verify the concordance of the treatment effect with the publication and to assess the LIPI prognostic and predictive value according to the treatment arms of each study (some requested studies are not randomized). Then, we will pool the studies in order to analyse the global prognostic value of LIPI and to gain power for the predictive analysis.
MISSING DATA HANDLING
As we will have access to prospective trials, we think that the missing data rate will be low.
We will perform our statistical analyses on the raw dataset first. Then we will dot a sensitivity analysis with imputation of the missing data in order to confirm our first results.
Requested Studies:
A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02008227
Sponsor ID: GO28915
Phase 2 Study of Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib in Patients With Untreated Extensive Stage Small Cell Lung Cancer
Data Contributor: Project Data Sphere
Study ID: NCT03041311
Sponsor ID: G1T28-05
A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Carboplatin+Nab-Paclitaxel in Chemotherapy-Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367794
Sponsor ID: GO29437
A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367781
Sponsor ID: GO29537
A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02366143
Sponsor ID: GO29436
A Phase II, Multicenter, Single-Arm Study OF Atezolizumab In Patients With PD-L1-Positive Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02031458
Sponsor ID: GO28754
A Phase II, Open-label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of MPDL3280A (Anti−PD-L1 Antibody) Compared With Docetaxel in Patients With Non−Small Cell Lung Cancer After Platinum Failure
Data Contributor: Roche
Study ID: NCT01903993
Sponsor ID: GO28753
A Phase II, Multicenter, Single-arm Study of MPDL3280A in Patients With PD-L1-Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT01846416
Sponsor ID: GO28625
Public Disclosures:
- M. Roulleaux Dugage, M. Tagliamento, T. Gorria, A. Rochand, L. Garcin, S. Oudard, C. Thibault, V.M. Albarran Artahona, J.C. Laguna Montes, I. Nalda Ariza, F.J. Muñoz i Carrillo, L. Aguilar, A. Arcocha, L. Lupinacci, C. Teixido, B. Besse, L. Mezquita, E. Auclin. 1450P – Addition of bevacizumab to first-line chemoimmunotherapy in NSCLC with liver metastases. Annals of Oncology (2023) 34 (suppl_2): S755-S851. doi: 10.1016/annonc/annonc1331
- M. Roulleaux Dugage, T. Gorria, A. Rochand, L-M. Garcin, S. Oudard, V. Albarrán-Artahona, J.C. Laguna, I. Nalda, F.J. Muñoz-Carrillo, L. Aguilar, A. Arcocha, L. Lupinacci, C. Teixidó, B. Besse, L. Mezquita, E. Auclin. Lung Immune Prognostic Index Predicts Outcomes from Upfront Chemotherapy + Immunotherapy +/- Antiangiogenic in Advanced NSCLC. World Conference on Lung Cancer. (2023).