Abstract 5783
Background
Six anti–PD-1/PD-L1 agents have been FDA approved for various cancers. Despite a lack of head-to-head trials, there is a perception that the irAE profiles are comparable between agents. We hypothesized that the irAE profiles vary between anti–PD-1 and anti–PD-L1 agents and among individual agents. Since prospective comparison is unlikely, we conducted a trial-level meta-analysis of irAEs reported in phase I–IV trials evaluating anti–PD-1/L1 agents in various tumor types.
Methods
We analyzed data from 35 manuscripts reporting phase I (n = 18), 2 (n = 15), 3 (n = 9) or 4 (n = 1) trials, comprising 8,730 patients treated with anti–PD-1/PD-L1 monotherapy. The incidence and odds ratios (ORs) for selected clinically relevant irAEs (colitis, elevated AST, hypothyroidism, pneumonitis or rash; any grade and grade ≥3) and irAEs overall were estimated using random-effects models for anti–PD-L1 agents atezolizumab, avelumab and durvalumab; for anti–PD-1 agents nivolumab and pembrolizumab; and as pooled estimates for anti–PD-1 and anti–PD-L1 agents.
Results
The risk of any grade (OR = 4.34) and grade ≥3 rash (OR = 4.38); grade ≥3 hypothyroidism (OR = 2.85); any grade (OR = 2.53) and grade ≥3 colitis (OR = 3.79); and any grade ≥3 irAE (OR = 1.89) was higher with anti–PD-1 vs anti–PD-L1 agents. When comparing the risk of all selected irAEs for each agent with pooled estimates for all other agents combined, atezolizumab had the lowest risk, followed by avelumab; pembrolizumab had a higher risk, except for grade ≥3 elevated AST. In pairwise comparisons, the risks associated with atezolizumab vs avelumab were not significantly different, likewise for nivolumab vs pembrolizumab. The largest decrease in risk for all grade ≥3 irAEs except elevated AST was for avelumab vs pembrolizumab.
Conclusions
Overall, the risk of grade ≥3 irAEs was higher with anti–PD-1 vs anti–PD-L1 agents. Compared with other agents, avelumab had a lower risk of individual grade ≥3 irAEs except elevated AST, whereas atezolizumab had the lowest risk of irAEs of any grade. Limitations include the retrospective nature of the meta-analysis and varied tumor types, trial designs, treatment durations and irAE evaluations.
Clinical trial identification
Editorial acknowledgement
ClinicalThinking, funded by Merck Healthcare KGaA and Pfizer Inc.
Legal entity responsible for the study
Merck Healthcare KGaA.
Funding
Merck Healthcare KGaA and Pfizer Inc.
Disclosure
G.P. Sonpavde: Honoraria (self): UpToDate; Advisory / Consultancy: Agensys; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Eisai; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Merck & Co.; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Speaker Bureau / Expert testimony: Clinical Care Options/NCCN; Speaker Bureau / Expert testimony: Onclive; Speaker Bureau / Expert testimony: Physician Education Resource; Speaker Bureau / Expert testimony: Research to Practice; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Onyx; Research grant / Funding (institution): Pfizer. P. Grivas: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Biocept; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy: Driver, Inc; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Heron; Advisory / Consultancy, Research grant / Funding (institution): Merck & Co.; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: QED Therapeutics; Advisory / Consultancy: Seattle Genetics; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Oncogenex. D. Hennessy: Full / Part-time employment: EMD Serono. J.D. Hunt: Full / Part-time employment: EMD Serono. All other authors have declared no conflicts of interest.
Resources from the same session
2115 - Preclinical in vivo screening to predict responder patients depend on EGFR status
Presenter: Yejin Kim
Session: Poster Display session 3
Resources:
Abstract
3349 - Interplay between miR-17-5p and MALAT-1 Shapes The Cytokine Storm in Triple Negative Breast Cancer (TNBC) Tumor Microenvironment
Presenter: Raghda Soliman
Session: Poster Display session 3
Resources:
Abstract
4014 - Clinical verification on the relationship between lipid metabolism and the immune microenvironment of breast cancer
Presenter: Wataru Goto
Session: Poster Display session 3
Resources:
Abstract
4158 - The clinical and transcriptional signatures of human CD204 reveal an applicable marker for tumor associated macrophage in breast cancer
Presenter: Yunjie He
Session: Poster Display session 3
Resources:
Abstract
5392 - Activated effector T cells co-expressing multiple inhibitory receptors (IRs) are enriched in the tumor immune microenvironment in high grade serous ovarian cancer (HGSOC)
Presenter: Alice Bergamini
Session: Poster Display session 3
Resources:
Abstract
2617 - Oncolytic reovirus as a new anti-tumor strategy in castration resistant prostate cancer
Presenter: Yunlim Kim
Session: Poster Display session 3
Resources:
Abstract
2995 - Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21
Presenter: Ali Memarian
Session: Poster Display session 3
Resources:
Abstract
3597 - Myeloid derived suppressor cells but not regulatory T cells are associated with adaptive immunity and clinical outcomes in anal squamous cell carcinoma
Presenter: Christophe Borg
Session: Poster Display session 3
Resources:
Abstract
3430 - Evaluation of immune responses among responders (R) and non-responders (non-R) in a humanized mouse model with colorectal cancer (CRC) xenografts treated with combination immunotherapy
Presenter: Juan Marín Jiménez
Session: Poster Display session 3
Resources:
Abstract
1995 - ¬¬Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy
Presenter: Hansol Lee
Session: Poster Display session 3
Resources:
Abstract