Cancer vaccines (CVs) represent a long-sought therapeutic and prophylactic immunotherapy strategy to obtain antigen (Ag)-specific T-cell responses and potentially achieve long-term clinical benefit. ...However, historically, most CV clinical trials have resulted in disappointing outcomes, despite promising signs of immunogenicity across most formulations. In the past decade, technological advances regarding vaccine delivery platforms, tools for immunogenomic profiling, and Ag/epitope selection have occurred. Consequently, the ability of CVs to induce tumor-specific and, in some cases, remarkable clinical responses have been observed in early-phase clinical trials. It is notable that the record-breaking speed of vaccine development in response to the coronavirus disease-2019 pandemic mainly relied on manufacturing infrastructures and technological platforms already developed for CVs. In turn, research, clinical data, and infrastructures put in place for the severe acute respiratory syndrome coronavirus 2 pandemic can further speed CV development processes. This review outlines the main technological advancements as well as major issues to tackle in the development of CVs. Possible applications for unmet clinical needs will be described, putting into perspective the future of cancer vaccinology.
•CVs have been characterized by positive safety and immunogenicity profiles but low levels of clinical efficacy.•Novel CV strategies entail personalized formulations and effective combinatorial regimens.•Positive momentum from the coronavirus disease-2019 vaccination campaign can in turn accelerate CV clinical testing.
Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 ...antibody–drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement.
•Targeting HER2-low expression with novel antibody-drug conjugates has reshaped the treatment of metastatic breast cancer.•This advancement raised relevant questions pertaining to the definition, diagnosis and management of HER2-low breast cancer.•We gathered 32 international experts to build consensus regarding key controversial topics pertaining HER2-low breast cancer.•A modified Delphi voting methodology was deployed, leading to 20 consensus statements, each with at least 90% consensus among experts.•Ongoing studies may lead to further refinement in our understanding of HER2-low breast cancer.
Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptors family, having as its main ligands neuregulins 1 and 2. Although its poor tyrosine kinase ...activity entails a weak oncogenic power on its own, HER3 can heterodimerize with HER2 and/or epidermal growth factor receptor (EGFR), leading to a drastic enhancement of transphosphorylation and activation of downstream signaling pathways, ultimately promoting oncogenesis, metastatic dissemination, and drug resistance. Given its ubiquitous expression across solid tumors, multiple efforts have been done to therapeutically target HER3 by blocking either the ligand binding domain or its dimerization with other receptors. Treatment with anti-HER3 monoclonal antibodies or bispecific antibodies, both as single agents and in combination with other compounds, unfortunately led to unsatisfactory results across several tumor types. The HER3-directed delivery of cytotoxic payloads through antibody-drug conjugates has recently demonstrated encouraging activity in several tumor types, however, suggesting a potential role for the therapeutic targeting of HER3 in cancer treatment.
•HER3 is a tyrosine kinase receptor belonging to the HER family, ubiquitously expressed across different solid tumors.•HER3 has a role in tumorigenesis, disease progression, metastatic dissemination and anticancer drugs’ resistance.•Monoclonal antibodies and bispecific antibodies targeting HER3 have led to unsatisfactory results.•More promising results have been observed with novel ADCs, although burdened with hematologic and serious pulmonary toxicity•Biomarkers of response to HER3-directed agents need to be explored and prospectively validated.
•We explored the role of adjuvant chemotherapy in the treatment of patients with localized lobular breast cancer (ILC)?•In this systematic review of the literature and metanalysis, a role of the ...adjuvant chemotherapy in the setting of ILC was not confirmed. The analysis on 38,387 patients across 8 studies did not show an additional benefit of chemotherapy (Hazard Ratio for Overall Survival: 0.99; 95%CI 0.86–1.14). However, all the investigations were retrospective, and subgroup analyses in high-risk patients showed some signals of possible adjunctive benefits.•Prospective investigations of adjuvant therapies in high-risk patients with ILC are highly warranted. The current decision- making is largely based on evidence from non-randomized clinical investigations, prompting controlled clinical studies.
The role of adjuvant chemotherapy (aCT) for patients with localized lobular breast cancer (ILC) is still controversial. It is unclear what is the magnitude of benefit of the CT in this setting. In this systematic review of the literature and metanalysis, we aimed to estimate the benefit of aCT in addition to the standard treatments in the early ILC setting. We identified the records by searching Medline, CENTRAL, Web of Science, SCOPUS, and Google Scholar, and the meeting proceeding of the principal oncology meetings of the last 10 years, with no language or time restriction. A research strategy was developed with mapped and MeSH terms. Studies on the clinical use of aCT reporting survival outcomes in the ILC setting were double-screened and tabulated. PRISMA methodology was used for data extraction and synthesis. We extracted information on the study design and setting, eligible population and population size, histology variants, menopausal status, treatment regimens, follow-up duration. Hazard ratios (HR) and 95% confidence interval (CI) were extracted and transformed into logHR and corresponding standard error to obtain the Summary HR (SHR). Heterogeneity (I2 statistics) and publication bias (Macaskill test) were tested; a random effect models provided by SAS Proc Mixed was used for data analysis. Sensitivity analysis was conducted to examine the impact of inclusion criteria on the summary results.
Disease-free (DFS), overall (OS) and cancer-specific survival (BCSS) were the primary endpoints of the investigation. The systematic review and metanalysis included 38,387 patients across 8 clinical studies. aCT was not associated with an improvement of OS (SHR 0.99; 95%CI 0.86–1.14), with low heterogeneity (I2 = 28%) and no publication bias (p = 0.43). Sensitivity analysis resulted in unchanged conclusions. We did not perform a metanalysis of the DFS estimates, as only reported in 3 studies. The value of aCT in improving DFS was unconfirmed, consistently with the OS results. Our research did not confirm a certain role of aCT for patients with ILC. Research gaps were identified, warranting the development of prospective, controlled ad hoc investigations.
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