Lead Investigator: Qian Chen, Hubei Cancer Hospital
Title of Proposal Research: Retrospective analysis of the effect of first-line bevacizumab treatment on survival and prognosis of patients with advanced non-small cell lung cancer treated with second-line immunotherapy
Vivli Data Request: 6758
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Lung cancer is the leading cause of cancer death globally, and outcomes for patients diagnosed with advanced non-small-cell lung cancer (NSCLC) are poor despite recent advances in treatment. Chemotherapy is one of the basic treatments by using one or more cytotoxic drugs to destroy or inhibit the growth and division of malignant cells. However, the efficacy of chemotherapy in NSCLC is limited. At present, there is a lot of evidence that the combination of anti-angiogenic drugs with chemotherapy can further prolong the survival time of patients. Angiogenesis is defined as the formation of new blood vessels from preexisting vessels and has been characterized as an essential process for tumor cell proliferation and viability. The mechanism of anti-angiogenesis drugs is to disrupt the vascular supply and starve tumor of nutrients and oxygen, primarily through blockade of VEGF/VEGFR signaling. Bevacizumab is the first available anti-angiogenic agent, which can block the interaction of vascular endothelial growth factor (VEGF) with its receptors, thereby inhibiting the activation of VEGF signaling pathways that tumor blood vessel development.
In recent years, Immunotherapy, which harnesses the power of the immune system of human body to fight against cancer, has changed the landscape of cancer therapy. The most effective immunotherapy agents currently used against advanced NSCLC are drugs known as checkpoint inhibitors, which are antibodies blocking PD-1 or PD-L1. PD-1 is a protein found on T cells in the blood. T cells are an important part of the body’s immune response, attacking foreign particles. When PD-1 is bound to another protein, PD-L1, it stops T cells from attacking foreign cells such as cancer cells. However, the efficacy for anti-PD-1/PD-L1 immunotherapy is relatively low (objective response rate <20%). Pre-clinical studies have shown that anti-angiogenic drugs, such as bevacizumab, are able to boost the immune system and improve the efficacy of immunotherapy. Therefore, we will explore whether the use of anti-angiogenic drugs followed by immunotherapy can further improve the survival of patients.
Statistical Analysis Plan:
Baseline patient characteristics of the pooled population were recorded according to use of bevacizumab and second-line immunotherapy drugs. Variables for the statistical model were selected based on their prognostic values in non-small-cell lung cancer (NSCLC), and included age, sex, race, Eastern Cooperative Oncology Group (ECOG), performance status (PS 0-1), tobacco use, histology (non-squamous, squamous), immune cell score, and number of prior therapies.
The study endpoints were patient response rate (ORR), progression free survival (PFS) and overall survival time (OS) which were first identified by a screening process via univariate Cox models. The response rate endpoint will be assessed through the estimation of individual odds ratios within each subgroup. The PFS and OS endpoints will be assessed with Kaplan-Meier curves and log-rank test. The Cox’s proportional hazards model will be used to calculate the hazard ratio and 95% Confidence Interval. Multivariate analysis will be performed using Cox’s model, adjusting for age, sex, performance status (ECOG), PD-L1 status. Variables with a P value ＜0.15 were then tested in separate multivariate Cox models. Additionally, HRs for subgroup analyses and within treatment effects were evaluated with an unstratified Cox model. Logistic regression modelling will be used to assess the impact of prior anti-angiogenic therapy. Also, a multivariate analysis will be performed using logistic regression modeling, adjusting for age, sex, performance status (ECOG), PD-L1 status. All statistical tests will be two-sided. For the primary objective, we will consider a P-value <0.05 as statistically significant.
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
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 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
Public Disclosures:
Chen, Q., Yuan, S., Liu, N., Wang, H., Shang, X., Ma, X., Sun, Y., Wei, C., Liu, L., Wang, X. and Liu, Y. Effect of first-line bevacizumab on prognosis of second or later-line immunotherapy in patients with advanced non-squamous non-small cell lung cancer: A retrospective analysis. JCO 42, 20570. (2024). Doi :10.1200/JCO.2024.42.16_suppl.e20570