Efficacy of cancer vaccines in selected gynaecological breast and ovarian cancers: A 20-year systematic review and meta-analysis.

BACKGROUND

Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far.

DESIGN

A systematic review and meta-analysis was conducted to evaluate vaccines' efficacy on breast cancer (BC) and ovarian cancer (OC) patients. Our search was based on the PubMed electronic database, from 1st January 2000 to 4th February 2020.

OBJECTIVE

response rate (ORR) was the primary end-point of interest, while progression-free survival (PFS), overall survival (OS) and toxicity were secondary end-points. Analysis was performed separately for BC and OC patients. Pooled ORRs were estimated by fixed or random effects models, depending on the detected degree of heterogeneity, for all studies with more than five patients. Subgroup analyses by vaccine type and treatment schema as well as sensitivity analyses, were implemented.

RESULTS

Among 315 articles initially identified, 67 were eligible for our meta-analysis (BC: 46, 1698 patients; OC: 32, 426 patients; where both BC/OC in 11). Dendritic-cell and peptide vaccines were found in more studies, 6/10 BC and 10/13 OC studies, respectively. In our primary BC analysis (21 studies; 428 patients), the pooled ORR estimate was 9% (95%CI[5%,13%]). The primary OC analysis (12 studies; 182 patients), yielded pooled ORR estimate of 4% (95%CI[1%,7%]). Similar were the results derived in sensitivity analyses. No statistically significant differences were detected by vaccine type or treatment schema. Median PFS was 2.6 months (95% confidence interval (CI)[1.9,2.9]) and 13.0 months (95%CI[8.5,16.3]) for BC and OC respectively, while corresponding median OS was 24.8 months (95%CI[15.0,46.0]) and 39.0 months (95%CI[31.0,49.0]). In almost all cases, the observed toxicity was only moderate.

CONCLUSION

Despite their modest results in terms of ORR, therapeutic vaccines in the last 20 years display relatively long survival rates and low toxicity. Since a plethora of different approaches have been tested, a better understanding of the underlying mechanisms is needed in order to further improve vaccine efficacy.

Informations de copyright

Copyright © 2020. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Conflict of interest statement UD has served as advisor/consultant for Roche. GC has received grants, research support and/or is coinvestigator in clinical trials by BMS, Celgene, Boehringer Ingelheim, Roche, Iovance and Kite; has received honoraria for consultations or presentations by Roche, Genentech, BMS, AstraZeneca, Sanofi-Aventis, Nextcure and GeneosTx; has patents in the domain of antibodies and vaccines targeting the tumour vasculature as well as technologies related to T-cell expansion and engineering for T-cell therapy; and receives royalties from the University of Pennsylvania related to T-cell therapy. KZ has provided consulting or participation in advisory boards of: AstraZeneca, Daiichi, Genomic Health (Exact Science), Lilly, MSD, Mylan, Novartis, Pfizer, Roche; has received travel funding by AstraZeneca, Pfizer, Roche, Pierre Fabre; has unrestricted funding for organisation of scientific events by AstraZeneca, Daiichi, Eisai, Exact Science, Lilly, MSD, Mylan, Novartis, Pfizer, Roche, Synlab; has research funding by Roche. AS has served as advisor/consultant for Roche, AstraZenca, Tesaro-GSK, Celgene-BMS; has received travel/educational/research grants by Roche, AstraZenca-MSD, GSK, Celgene, Agen, BMS, Pfizer, Clovis, Novartis. LK has received grants in clinical trials by BMS, BTG and Nestle.; has received honoraria for consultations GeneosTx. All remaining authors have declared no conflicts of interest.