Oncotarget

Reviews:

Comparative safety analysis of immunotherapy combined with chemotherapy versus monotherapy in solid tumors: a meta-analysis of randomized clinical trials

Alberto Carretero-González, David Lora, Ismael Ghanem, Irene Otero, Flora López, Daniel Castellano and Guillermo de Velasco _

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Oncotarget. 2019; 10:3294-3301. https://doi.org/10.18632/oncotarget.26908

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Abstract

Alberto Carretero-González1, David Lora2, Ismael Ghanem3, Irene Otero1, Flora López1, Daniel Castellano1 and Guillermo de Velasco1

1 Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain

2 Clinical Research Unit (imas12-CIBERESP), University Hospital 12 de Octubre, Madrid, Spain

3 Medical Oncology Department, University Hospital La Paz, Madrid, Spain

Correspondence to:

Guillermo de Velasco,email: gdvelasco.gdv@gmail.com

Keywords: immunotherapy; chemotherapy; combination treatment; safety profile; adverse events

Received: January 31, 2019     Accepted: April 21, 2019     Published: May 14, 2019

ABSTRACT

Background: Combination treatment (chemotherapy plus immune checkpoint blockade [ICB]) has shown promising activity in terms of efficacy, but it has been suggested that its toxicity profile is less favorable compared to monotherapy.

Methods: We conducted a meta-analysis of published randomized clinical trials comparing combination treatment to monotherapy (chemotherapy or ICB) in patients with metastatic solid tumors. Differences in rates of safety issues (all-grade adverse events, grade 3/4 adverse events, treatment-related deaths, treatment discontinuations) between groups were estimated. Subgroup analyses for the control group (chemotherapy or ICB as monotherapy) and immune checkpoint inhibitor (anti-CTLA-4 or anti-PD-1/PD-L1 antibodies) were performed.

Results: A total of 4379 patients (ten studies) were included (monotherapy: 2026 patients; combination treatment: 2353 patients). Combination treatment presented more grade 3/4 adverse events (RR 1.32, 95% CI 1.12–1.55) and discontinuations (RR 2.31, 95% CI 1.28–4.16). There were no differences in the mortality rate between groups. Subgroup analyses showed a potentially more toxic profile with anti-CTLA-4 agents.

Conclusions: Combination treatment is associated with an increase in grade 3/4 adverse events and treatment discontinuations compared to monotherapy, but not increased mortality. The toxicity profile of combination therapy should be considered with regard to the overlapping safety profiles.


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