Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity, and cost-effectiveness.
Expert commentary: The combination of trastuzumab/pertuzumab is approved in all disease settings, while trastuzumab/neratinib is approved in the adjuvant setting and trastuzumab/lapatinib in metastatic disease. Meanwhile, as breast cancer biology and resistance mechanisms become clearer, combinations with drugs like PI3K/Akt/mTOR inhibitors, CDK4/6 inhibitors, anti-PD(L)1 antibodies, endocrine therapy, and new anti-HER2 agents (panHER and HER2 tyrosine kinase inhibitors, bispecific antibodies, anti-HER3 antibodies, and antibody-drug conjugates) are being extensively tested in clinical trials. More specific strategies for the ‘triple-positive’ (estrogen receptor-positive/HER2-positive) disease are also being explored. However, there is an urgent need for the development of predictive biomarkers for a better tailoring of anti-HER2 directed therapy. This is the only way to further improve clinical outcomes and quality of life and to decrease costs and toxicities of unnecessary treatments. 相似文献
Areas covered: Anti-HER2 targeting drugs such as trastuzumab, pertuzumab, and T-DM1 have shown significant results in (neo)adjuvant setting. In this article, we will focus on available data for neratinib to reduce BC recurrence based mainly on the results of the ExteNET trial. This trial aimed to investigate whether neratinib can further reduce the risk of recurrence of patients diagnosed with HER2-positive BC. This trial demonstrated a significant reduction in the risk of invasive disease-free survival, particularly in hormone receptor-positive population. In addition, this review provides an expert opinion and analysis of the current situation in the adjuvant HER2-positive BC setting and in particular the escalation strategy of HER2 targeting.
Expert opinion: The treatment landscape of HER2 positive BC in this setting will evolve in the coming years with a need for clinical and molecular perspective tools to guide therapy. 相似文献
Areas covered: Here we look at the clinical relevance of pCR and compare rates of total pCR (defined as ypT0/is ypN0) and breast pCR (defined as ypT0/is) in clinical trials of reference and biosimilar trastuzumab.
Expert commentary: In order to evaluate the efficacy of neoadjuvant systemic therapies in a uniform way, standardization of trial endpoints is necessary. Future studies in HER2-positive breast cancer should include full assessment of the breast and lymph node basin before and after neoadjuvant systemic therapy, and the use of total pCR as the primary outcome. 相似文献
Areas covered: There are ongoing efforts to augment further the use of targeted agents as adjuvant treatment in BC, hoping that early introduction of targeted therapy blocking key oncogenic drivers of micro-residual disease, will significantly improve clinical outcomes. In the present Review, we present data through extensive search of PubMed about the following targeted adjuvant therapeutic strategies in BC: i) HER2 blockade and ongoing efforts to further augment its efficacy for patients with HER2-positive disease, ii) angiogenesis inhibition, iii) PI3K-mTOR- AKT pathway inhibition, iv) CDK4/6 inhibition, v) PARP inhibition.
Expert commentary: we provide insights about challenges and potential ways to overcome them, in terms of successful clinical development of targeted agents as adjuvant therapy for patients with BC. In particular, we emphasize the need to systematically assess minimal residual cancer burden as a way to increase the rates of successful clinical development of targeted agents in the adjuvant setting. 相似文献
Areas covered: This review gives an overview of available preclinical and clinical data regarding olaparib, including its chemistry, mechanism of action, pharmacokinetics and pharmacodynamics, and evidence supporting antitumor efficacy and safety profile in breast cancer patients.
Expert commentary: Olaparib improves progression-free survival in germline BRCA mutated HER2 negative metastatic breast cancer patients as compared to standard chemotherapy, with a manageable toxicity profile. Efficacy is of clinical relevance especially in the context of triple negative breast cancer. However, several aspects, such as sequencing or combination of these agents with other anticancer agents and identification of appropriate biomarkers, still need to be clearly defined. 相似文献
Areas covered: This review presents the main achievements in the systemic treatment of IBC during the past 30 years. It focuses more specifically on recent results obtained with targeted therapies, including anti-HER2 and anti-angiogenic agents. Novel approaches under investigation are presented.
Expert commentary: Current management of IBC is subtype-specific and the largest benefit has been achieved in HER2-positive disease. The identification of breakthrough therapeutic advances is eagerly awaited and will require the development of IBC-specific clinical trials. Future clinical investigations should not only aim to increase the pathological response rate but also to eradicate distant metastases, which ultimately lead to patient death. 相似文献
Areas covered: This review covers the major randomized European and Canadian trials comparing HF-WBI to CF-WBI with long-term follow-up, as well as additional recently closed randomized trials that further seek to define the applicability of HF-WBI in clinical practice. Randomized data is summarized in terms of clinical utility and for a variety of clinical applications. Recently published consensus guidelines and practical implementation of HF-WBI including its broader effect on the healthcare system are reviewed. Finally, an assessment of the emerging evidence in support of hypofractionation for locally advanced disease is presented.
Expert commentary: HF-WBI has replaced CF-WBI as the accepted standard of care in most women with early-stage breast cancer who do not require regional nodal irradiation. Early data supports the continued study of hypofractionation in the locally advanced setting, however broad adoption awaits longer follow-up and additional data from ongoing clinical trials. 相似文献
Areas covered: The present review summarizes the current progress and future directions for HER2 targeted therapies in GI cancers, including esophagogastric, pancreaticobiliary, and colon cancers. To date trastuzumab is the only anti-HER2 therapy approved for metastatic esophagogastric adenocarcinoma. Efforts are ongoing to expand the therapeutic role of HER2 to other GI cancers and overcome mechanisms of drug resistance. Novel agents and combinations are being tested in most HER2 positive GI cancers including early stage disease. These are of recent interest in colorectal cancer with studies indicating that HER2 overexpression might increase resistance to anti-EGFR therapy and may be potentially targeted.
Expert commentary: With the current ability to sequence tumors and detect genetic alterations, emphasis should be put on genomically-selected pan-tumor targeted therapies. HER2 is a perfect example of a promising drug target in GI cancers. 相似文献
Areas covered: This article discusses the journey of fulvestrant licensing, its efficacy in combination with other endocrine therapies and the future role it may have within breast cancer treatment.
Expert commentary: Within phase III trials, fulvestrant has demonstrated equivalent or improved clinical efficacy when compared with established endocrine agents. In the recent decade, fulvestrant has achieved licensing as a second line agent in non-operative advanced breast cancer at initially 250mg, increasing to 500mg. Presently, fulvestrant is licensed globally as first line endocrine management for advanced breast cancer in post-menopausal women. Early combination trials of fulvestrant and cyclin dependent kinase 4/6 inhibitors have demonstrated good clinical efficacy with improved progression free survival when compared to fulvestrant alone. 相似文献
Areas covered: This review aims to summarize the data from clinical trials assessing the effect of BMI on response to AI-based therapy in the setting of breast cancer.
Expert commentary: Our conclusion made on the data available to date does not exclude BMI from the list of potential predictive factors however further research in this area is warranted. 相似文献
Areas covered: Herein we evaluate the new molecular proposal of gastric cancer classification, offering the possibility to recognize different pathogenetic mechanisms and molecular biomarkers potentially useful for target therapies.
Expert commentary: The possibility of introducing new specific tests for identification of molecular biomarkers critical for targeted therapies response represents the new frontier in the selection of gastric cancer patients to improve their survival. Besides HER2, already used in clinical settings as a target biomarker for biological therapy in gastric cancer patients with tissue cancer cells overexpressing HER2, other promising target biomarkers which are deregulated in gastric cancer, such as MET and FGFR, could be identified in tissue and then used for therapeutic purposes. In addition immunotherapy represents the most promising possibility of advanced gastric cancer treatment. In particular, as in other solid tumors, PD-1/PDL1 pathway has emerged in several clinical trials as an interesting therapeutic target. 相似文献
Areas covered: In this review, we discuss hormone resistance and strategies to overcome it, from the pre-clinical and clinical perspectives. This review includes a discussion of inhibition of the PI3K/AKT/mTOR, CDK 4/6, histone deacetylation, fibroblast growth factor receptor, and immune pathways, based on review of relevant literature.
Expert commentary: Several emerging novel therapies to improve the response to hormone therapy are approved or are in development. The most promising agents at present are inhibitors of CDK 4/6 and mTOR, which have already been incorporated into treatment in the advanced stage setting and are under study for early stage disease. 相似文献
Areas covered: In this paper, we present an in depth overview on the state of the art on these key issues of refining decision-making in adjuvant anti-HER2 therapy.
Expert commentary: Despite many important research efforts in the field, chemotherapy plus trastuzumab for a total duration of 1 year remains the standard of care. However, recent data showed that besides standard anthracycline- and taxane-based cytotoxic therapy, alternative chemotherapy regimens can now be proposed to patients with small tumors without nodal involvement and to women at high-risk of developing cardiotoxicity. Of note, besides HER2 itself, biomarkers predicting patients who may truly benefit from anti-HER2 agents are still lacking. 相似文献
Areas covered: This review examines the spectrum and consequences of adverse effects of tamoxifen and aromatase inhibitors, and the pharmacological and non-pharmacological approaches to mitigate some of the most frequent and disturbing side effects of endocrine therapy (including vasomotor, musculoskeletal, and vulvovaginal symptoms). The authors performed a qualitative analysis of English papers indexed in PubMed through May 2017, including meta-analysis, randomized controlled trials, observational studies, and systematic reviews.
Expert commentary: Side effects of endocrine treatments are frequent and often underestimated in the care of breast cancer survivors, leading to a poor adherence to treatments that can compromise oncological outcomes. Many of the most common adverse events can be mitigated through pharmacological and non-pharmacological approaches that should be discussed and offered to patients in a dedicated setting of care. 相似文献
Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of systemic treatment of metastatic colorectal cancer. This article reviews the current evidence for targeted therapies in advanced colorectal cancer, including up-to-date data regarding anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF) agents, the relevance of primary tumor location and novel subgroups such as BRAF mutated, HER2 amplified, and mismatch-repair-deficient cancers.
Expert commentary: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for metastatic colorectal cancer (mCRC). The use of EGFR-targeted antibodies should be restricted to patients with extended RAS wild-type profiles, and there is evidence that they should be further restricted to patients with left-sided tumors. Clinically, mCRC can be divided into subgroups based on RAS, BRAF, HER2, and MMR status, each of which have distinct treatment pathways. 相似文献
Areas covered: The review provides an overview on the significance of the presence of the T790M mutation, its detection, treatment options and subsequent mechanisms of resistance.
Expert commentary: Osimertinib is the current treatment option for T790M mutation positive NSCLC after progression to first or second-generation EGFR TKIs, with activity also on brain metastasis. However, the scenario is in continuous evolution and results from clinical trials are awaited in first-line setting and in combination strategies. 相似文献
Areas covered: In this review, the authors have concisely explained doxorubicin chemotherapy and the photobiological processes of phthalocyanine triggered photodynamic therapy (PDT). A literature search was conducted and reports demonstrating the use of doxorubicin and photodynamic therapy as a treatment modality for breast cancer were identified. More emphasis was made on studies demonstrating the efficacy and improved anticancer effect of combining chemotherapy with photodynamic therapy. However, it was concluded that for this combination therapy, still in it’s infancy, it could be relevant when integrated into standard treatment.
Expert Commentary: To these effects, comprehensive models based on experimental evaluations are needed for rational design of anthracycline-based chemotherapy and PDT to be integrated into the clinical setting. 相似文献
Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers.
Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer. 相似文献
Areas covered: This review highlights how treatment-focussed genetic testing for BRCA1 and BRCA2 mutations can potentially influence cancer treatment and secondary prevention decisions in women with breast cancer.
Expert commentary: Testing women with breast cancer for BRCA1 and BRCA2 germline mutations has the potential to decrease cancer burden and improve cancer outcomes. It can help optimise surgical and systemic therapy approaches. Clinicians should actively consider whether genetic testing is appropriate for each woman with breast cancer, and if so should instigate it early in the treatment trajectory when it can most influence cancer care. 相似文献
A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC.
Methods: We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included.
Results: Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation.
Conclusion: There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed. 相似文献