Abstract 1357
Background
Among lung cancers, non- small cell lung cancer (NSCLC) accounts for approximately 80% of cases. It is one of the leading causes of cancer related mortality in US. Atezolizumab is a humanized monoclonal antibody against the programmed cell death-ligand 1 (PD-L1) protein. We have conducted a meta-analysis to evaluate the risk of first-line atezolizumab chemoimmunotherapy- associated immune-related adverse events (IRAEs) in patients with advanced NSCLC.
Methods
PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019 were queried. Phase III RCTs that mention IRAEs as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied.
Results
A total of 2725 patients with advanced NSCLC from four phase III RCTs were eligible. The study arm used standard chemotherapy regimens in combination with atezolizumab while control arm utilized only standard chemotherapy regimens. The RR of all-grade side effects were as follows: rash, 1.68 (95% CI: 1.13 – 2.50, p = 0.01); hepatitis, 2.57 (95% CI: 1.21– 5.49; p = 0.01); hypothyroidism, 6.27 (95% CI: 2.55 – 15.44, p < 0.0001); hyperthyroidism, 3.95 (95% CI: 1.77– 8.78; p = 0.0008); pneumonitis, 3.29 (95% CI: 1.98– 5.46; p < 0.0001); and colitis, 5.02 (95% CI: 1.74–14.50; p = 0.003). The RR of high-grade side effects were as follows: rash, 2.70 (95% CI: 1.20 – 6.10, p = 0.02); hepatitis, 4.35 (95% CI: 1.80– 10.51; p = 0.001); hypothyroidism, 3.51 (95% CI: 0.75 – 16.46, p = 0.11); hyperthyroidism, 2.48 (95% CI: 0.50– 12.25; p = 0.27); pneumonitis, 1.63 (95% CI: 0.72– 3.72; p = 0.24); and colitis, 3.86 (95% CI: 1.19–12.53; p = 0.02).
Conclusions
Our meta-analysis showed that the addition of atezolizumab to standard chemotherapy, contributed to higher incidence of all grades of rash, hepatitis and colitis with RR of 4.35 for grade 3 and 4 hepatitis. They also increased the risk of all-grade hypothyroidism, hyperthyroidism and pneumonitis. Timely intervention with proper supportive care will enhance patients’ quality of life, ultimately affecting patients’ compliance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5103 - CANOPY phase 3 program: Three studies evaluating canakinumab in patients with non-small cell lung cancer (NSCLC)
Presenter: Luis Paz-Ares
Session: Poster Display session 1
Resources:
Abstract
3666 - The Elderly Patient Individualized Chemotherapy (EPIC) trial, a study for an aged population of non-small cell lung cancer.
Presenter: Francesco Passiglia
Session: Poster Display session 1
Resources:
Abstract
4799 - KEYNOTE-495/KeyImPaCT: A Randomized, Biomarker-Directed, Phase 2 Trial of Pembrolizumab-Based Therapy for Non–Small Cell Lung Cancer (NSCLC)
Presenter: Martin Gutierrez
Session: Poster Display session 1
Resources:
Abstract
6035 - Safety, tolerability and activity of autologous T cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non small cell lung cancer: A Phase 1b/2a randomised pilot study
Presenter: Karen Reckamp
Session: Poster Display session 1
Resources:
Abstract
2176 - IFCT-1701 DICIPLE: a randomized phase 3 trial comparing continuation Nivolumab-Ipilimumab doublet immunotherapy until progression versus observation in patients with PDL1-positive stage IV Non-Small Cell Lung Cancer (NSCLC) after Nivolumab-Ipilimumab induction treatment
Presenter: Gerard Zalcman
Session: Poster Display session 1
Resources:
Abstract
2352 - ATALANTE-1 randomized phase 3 trial, OSE-2101 versus standard treatment as second or third line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
2451 - Phase Ib dose-escalation/expansion study of BI 836880, a VEGF/Ang2-blocking nanobody®, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumours
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
4285 - Radiosurgery followed by Tumor Treating Fields (TTFields) for brain metastases (1-10) from NSCLC in the phase 3 METIS trial
Presenter: Minesh Mehta
Session: Poster Display session 1
Resources:
Abstract
4909 - Nivolumab plus ipilimumab (NI) versus chemotherapy plus nivolumab (CN) in squamous cell lung cancer (SqCLC): the SQUINT trial
Presenter: Lorenza Landi
Session: Poster Display session 1
Resources:
Abstract
4125 - DUBLIN-3, a Stage IIIb/IV NSCLC Phase (Ph)3 Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone
Presenter: Ramon Mohanlal
Session: Poster Display session 1
Resources:
Abstract