Emerging treatments for HER2-positive early-stage breast cancer: Focus on neratinib

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib

A prospective, real‑world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN : a MASCC neutropenia, infection, and myelosuppression study group initiative

DATA AVAILABILITY : Novartis supports the publication of scientifically rigorous analysis that is relevant to patient care, regardless of a positive or negative outcome. Qualified external researchers can request access to anonymized patient-level data, respecting patient-informed consent, through www. clini calst udyda tareq uest. com, according to requirements noted on the web portal.PURPOSE : Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10–20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS : This prospective, real-world, observational, multinational, multicenter study (December 2016–October 2019) recruited patients with solid tumors or Hodgkin’s/non-Hodgkin’s lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS : In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2–3, and 1% in cycles 4–6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS : Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician’s judgement.Open access funding provided by University of Pretoria. This work was supported by research funding from Novartis Pharma AG, Basel, Switzerland.https://www.springer.com/journal/520am2024ImmunologySDG-03:Good heatlh and well-bein

Will modern immunotherapies become the standard of care for advanced synchronous or metachronous cancers?

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Immune checkpoint inhibitors side effects and management

The next decade in cancer therapy will be marked by the expansion of immunotherapies, namely immune checkpoint inhibitors. The increasing number and combination of checkpoint inhibitors and the variety of their mechanisms of action and indications will most likely multiply the side effects associated with these therapies and make their management more complicated and diversified. Given the growing rate of approval of different checkpoint inhibitors in different cancers in multiple settings, a review summarizing the major side effects of the new agents in use today and their management seems to be appropriate. Highlighting these adverse events and their management in a single review might help the daily practice of the physicians and consequently contribute the patient's safety and quality of life.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Physical long-Term side-effects in young adult cancer survivors: Germ cell tumors model

Purpose of review After the important advances in the treatment of germ cell tumors (GCTs) leading to high cure rates, physical long-Term side-effects represent an important cause of death in these young adult survivors. Highlighting these physical long-Term side-effects, their monitoring and their prevention modalities is necessary for a better management of these cancer survivors. Recent findings Impaired fertility, increased risk of developing a second cancer, cardiac, pulmonary, renal and neural toxicity, hearing and vision impairment are the major physical side-effects in young adult cancer survivors. Long-Term cardiac toxicity, next to second malignancies, represents life-Threatening conditions in testicular cancer survivors. The long-Term nephrotoxity in testicular GCTs survivors is most frequently associated to the treatment either in those treated with cisplatin-based chemotherapy, mainly Bleomycine, Etoposide, Cisplatin, or those receiving infradiaphragmatic radiation therapy, whereas pulmonary toxicity is mainly attributed to bleomycin related toxicities. Summary There are no clear and comprehensive data concerning the monitoring and prevention of long-Term side-effects in testicular cancer survivors. Physical activity and interventions in modifiable cardiovascular risk factors and lifestyles may reduce the incidence of long-Term side-effects in these cancer survivors.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Side-effects of checkpoint inhibitor-based combination therapy

Purpose of review After the dramatic and often long-standing response rates of checkpoint inhibitors as single agents, the new era for checkpoint inhibitors is combined therapy (either with other checkpoint inhibitors, chemotherapies, targeted therapies or immunotherapies) that is aiming to do even better. Although one can speculate that these combinations will result in improved results, high cost and potential toxicity are limiting factors for their use. In this review, we plan to report on the different side-effects of the checkpoint inhibitor-based combination therapies and to discuss the future perspectives of these new modalities. Recent findings Many checkpoint inhibitor-based combinations are associated with high response rates (>50%) in melanomas and nonsmall cell lung cancers (NSCLCs). As a result, the combination of nivolumab and ipilimumab for metastatic melanoma was recently approved by the Food and Drug Administration; however, 30% of the patients had to discontinue this combination because of high toxicity. In NSCLC, the combination of chemotherapy and anti-programmed cell death protein 1 or anti-programmed cell death protein ligand 1 agents is leading to high response rate (exceeding 65%) but with more than 40% of the patients presenting grade 3/4 toxicities. Despite the discouraging results with the combination of ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) with vemurafenib (anti-proto-oncogene protein B-raf-targeted therapy) due to hepatotoxicity, more recent trials are showing less frequent and severe toxicities with other combinations of checkpoint inhibitors and targeted therapies. Summary Despite the high toxicity rates observed with some checkpoint inhibitor-based combination therapies, these combinations will likely become the new paradigm for the management of various malignancies, namely, melanomas, renal cell carcinomas and NSCLC, provided that their side-effects can be effectively managed.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Why balls are not put inside the basket? A reflection on testicular cancer clinical trial design

New concepts of trial design are being developed based on biomarkers, namely basket and umbrella trials. Basket trials appear optimally positioned to evaluate new molecular markers for testicular germ cell tumors, a rare heterogeneous disease with relatively few molecular alterations. However, not uncommonly, the “balls” fall outside the “basket”. In this short communication, we discussed the different causes limiting the inclusion of TGCT in basket trials and we proposed a new design for trials suitable for this malignancy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Adding checkpoint inhibitors to tyrosine kinase inhibitors targeting EGFR/ALK in non-small cell lung cancer: a new therapeutic strategy

After the massive approval of checkpoint inhibitors in the treatment of numerous malignancies and settings, checkpoint inhibitors-based combination therapies are emerging as a new therapeutic modality. Nivolumab and pembrolizumab (anti-PD1 agents) were recently approved as second-line treatment in NSCLC after progression on platinum-doublets. In parallel, targeting EGFR/ALK in NSCLC using tyrosine kinase inhibitors (TKI) demonstrated remarkable outcomes and was approved as standard treatment, in patients with EGFR mutation or ALK rearrangement. Combining TKI targeting EGFR/ALK with checkpoint inhibitors seems a promising therapeutic option and is being evaluated in different trials. We aimed in this paper to elucidate the rationale behind this combination, to report the premilinary results of ongoing trials evaluating this association and finally, to discuss briefly the possible future indication of this treatment modality.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Rare side-effects of checkpoint inhibitors

Purpose of review The aim of this review is to draw the attention of the physicians and oncologists on the rare side-effects of checkpoint inhibitors not usually reported in clinical trials to treat them quickly and render their prognosis better. Recent findings Rare side-effects of checkpoint inhibitors are mainly neurologic, haematologic, rheumatologic, renal, and cardiac. The majority of reported side-effects are consequent of the treatment by ipilimumab in patients diagnosed with melanomas. Neurologic side-effects have poorer prognosis compared with other rare side-effects. There is no relationship between developing rare side-effects and the outcome of the disease. Summary It is important to be aware, when treating patients with checkpoint inhibitors, to detect as early as possible the unpredictable and uncontrollable rare side-effects of these agents. The large spectrum of these rare side-effects should be well documented and reported to assure to the physicians a road map for the diagnosis and the management of these toxicities.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Will gemcitabine monotherapy be dethroned as the adjuvant chemotherapy in pancreatic adenocarcinoma?

SCOPUS: re.jinfo:eu-repo/semantics/publishe