Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms

2018 ◽  
Vol 108 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Jaume Capdevila ◽  
Lisa Bodei ◽  
Philippa Davies ◽  
Vera Gorbounova ◽  
Robert T. Jensen ◽  
...  

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

2021 ◽  
Vol 9 (9) ◽  
pp. e003032
Author(s):  
James Harber ◽  
Tamihiro Kamata ◽  
Catrin Pritchard ◽  
Dean Fennell

Malignant pleural mesothelioma (MPM) is an incurable cancer with a dismal prognosis and few effective treatment options. Nonetheless, recent positive phase III trial results for immune checkpoint blockade (ICB) in MPM herald a new dawn in the fight to advance effective treatments for this cancer. Tumor mutation burden (TMB) has been widely reported to predict ICB in other cancers, but MPM is considered a low-TMB tumor. Similarly, tumor programmed death-ligand 1 (PD-L1) expression has not been proven predictive in phase III clinical trials in MPM. Consequently, the precise mechanisms that determine response to immunotherapy in this cancer remain unknown. The present review therefore aimed to synthesize our current understanding of the tumor immune microenvironment in MPM and reflects on how specific cellular features might impact immunotherapy responses or lead to resistance. This approach will inform stratified approaches to therapy and advance immunotherapy combinations in MPM to improve clinical outcomes further.


2009 ◽  
Vol 21 (S2) ◽  
pp. 27-34 ◽  
Author(s):  
Sven G. Meuth ◽  
Stefan Bittner ◽  
Heinz Wiendl

Abstract:Multiple sclerosis (MS) is regarded as a prototypic inflammatory autoimmune central nervous system disorder causing neurological disability in young adults. Recommended basic immunomodulatory therapies of MS are currently interferon beta and glatiramer acetate. Both have proven to be clinically and paraclinically effective and clinical evidence suggests that treatment should be initiated as early as possible.However, despite the fact that therapeutic options for MS have significantly been widened over the past decade there is still tremendous activity in the search for new treatment options for MS.One important development in the field is reflected by the substantial number of promising results for oral therapies. Various phase III clinical trials are currently being initiated or are already underway evaluating the efficacy of a variety of orally administered agents, including cladribine, teriflunomide, laquinimod, fingolimod and fumaric acid. It is hoped that these oral therapies for MS further broaden our armament for MS therapy.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
James Burton ◽  
Sebastian Walpen ◽  
Sandrine Danel ◽  
Lucy Snowdon ◽  
Bernd Schroeppel

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is a common yet under-recognised condition in patients with CKD undergoing haemodialysis (HD), in whom it is associated with reduced health-related quality of life (HRQoL), poor sleep quality, and a greater risk of depression. This real-world study obtained insights from nephrologists in Europe and Australia into the current practices, attitudes and unmet medical needs relating to the diagnosis and treatment of CKD-aP. Method Qualitative data were obtained from structured interviews conducted Oct–Nov 2019 with 72 nephrologists from France, Germany, Italy, Spain, UK and Australia (n=12 in each country). Quantitative data relating to diagnostic/treatment practices for CKD-aP were collected May–July 2020 by a 20-minute physician survey and collection of patient record forms (PRF). The survey was completed by 301 nephrologists from France (n=50), Germany (n=56), Italy (n=58), Spain (n=55), UK (n=52), and Australia (n=30). Respondents’ level of agreement was assessed using a 7-point scale, from 1 (do not agree at all) to 7 (strongly agree). PRF data were also captured for 1435 HD patients with CKD-aP from all countries. All nephrologists who completed the interviews and surveys were currently treating >5 HD patients with CKD-aP. Results Most nephrologists (75%) agreed that CKD-aP is under-diagnosed in HD patients, which is mainly driven by the lack of systematic screening by nephrologists and under-reporting of the condition by patients. The main barriers to screening for CKD-aP identified by nephrologists included the lack of diagnostic guidelines and absence of standardised pruritus intensity scales to consistently diagnose and classify CKD-aP severity. The majority (74%) agreed new clinical guidelines for nephrologists are needed to aid diagnosis. Nephrologists perceived that on average ∼34% of their HD patients experienced CKD-aP, and that 55% of them had moderate-severe symptoms. However, most nephrologists (79%) do not use any itch scales in clinical practice and 71% agreed a consistent international scale to diagnose CKD-aP is needed. 80% of nephrologists agreed diagnosis of CKD-aP is usually patient-driven, indicating there is a reliance on patients mentioning their symptoms. Less than half of nephrologists (46%) agreed that CKD-aP was easy to diagnose by clinical observation alone. The lack of targeted treatment guidelines and approved therapies for CKD-aP leads to an inconsistent, fragmented approach to management. Analysis of prescription data captured in the PRFs of 1435 HD patients with CKD-aP showed treatment in current clinical practice relies on incremental add-on therapy. The majority of patients (∼85-90%) receiving second- or subsequent lines of therapy for CKD-aP were prescribed combinations of different treatments. Commonly prescribed (off-label) medications for CKD-aP included antihistamines, moisturizers/emollients, corticosteroids and gabapentinoids. However, there was no single standard of care for the treatment of CKD-aP, highlighting the uncertainties nephrologists face relating to best treatment practice. Most nephrologists (72%) agreed that treatment options are very limited for patients with bothersome CKD-aP, and the survey responses indicated a high unmet need for novel treatments. The majority of nephrologists felt a major improvement was needed over current treatments, particularly in terms of improved efficacy for reduction of itch intensity (62%) and the ability to improve the patient HRQoL (57%). Conclusion This real-world international survey study of nephrologists showed that CKD-aP is a frequent, but under-diagnosed condition affecting many HD patients, with a lack of effective treatment options. Furthermore, there is an urgent need to develop guidelines to assist in the diagnosis of CKD-aP and new targeted treatment options that are both effective and well tolerated.


2021 ◽  
Vol 15 ◽  
pp. 117822342110024
Author(s):  
Élia Cipriano ◽  
Alexandra Mesquita

Metastatic triple-negative breast cancer (TNBC) is a heterogeneous disease with a poor prognosis and currently with few treatment options. Treatment of these patients is highly based on systemic chemotherapy. Some targeted drugs were recently approved for these patients: two poly(ADP-ribose) polymerase inhibitors in patients with germline BRCA1/2 mutations (olaparib and talazoparib), immune checkpoint inhibitors in association with chemotherapy if programmed death-ligand 1 positive (atezolizumab plus nabpaclitaxel and pembrolizumab plus chemotherapy [nabpaclitaxel, paclitaxel, and carboplatin plus gemcitabine]), and an antibody-drug conjugate sacituzumab-govitecan in heavily pretreated patients (at least 2 previous lines for the metastatic setting). Combinations using these and other targeted treatment options are under investigation in early and late clinical trials, and we will probably have some practice-changing results in the new future. Other targeted drugs explored in phase II and phase III clinical trials are PI3K/AKT pathway inhibitors and androgen receptor antagonists in patients with alterations in these signaling pathways. The definition of molecular subtypes has been essential for the development of these treatment strategies. Soon, the treatment of metastatic TNBC could be based on personalized medicine using molecular testing for targeted drugs instead of only systemic chemotherapy. The authors present a review of emerging treatment options in metastatic TNBC, focusing on targeted drugs, including the recent data published in 2020.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Eline M. Bunnik ◽  
Nikkie Aarts

Abstract Background Patients with unmet medical needs sometimes resort to non-standard treatment options, including the use of unapproved, investigational drugs in the context of clinical trials, compassionate use or named-patient programs. The views and experiences of patients with unmet medical needs regarding unapproved, investigational drugs have not yet been examined empirically. Methods In this qualitative study, exploratory interviews and focus groups were held with patients with chronic or life-threatening diseases (n = 39), about topics related to non-standard treatment options, such as the search for non-standard treatment options, patients’ views of the moral obligations of doctors, and the conditions under which they would or would not wish to use non-standard treatment options, including expanded access to unapproved, investigational drugs. Results Respondents had very little knowledge about and/or experience with existing opportunities for expanded access to investigational drugs, although some respondents were actively looking for non-standard treatment options. They had high expectations of their treating physicians, assuming them to be aware of non-standard treatment options, including clinical trials elsewhere and expanded access programs, and assuming that they would inform their patients about such options. Respondents carefully weighed the risks and potential benefits of pursuing expanded access, citing concerns related to the scientific evidence of the safety and efficacy of the drug, side effects, drug-drug interactions, and the maintaining of good quality of life. Respondents stressed the importance of education and assertiveness to obtain access to good-quality health care, and were willing to pay out of pocket for investigational drugs. Patients expressed concerns about equal access to new and/or non-standard treatment options. Conclusion When the end of a standard treatment trajectory comes into view, patients may prefer that treating physicians discuss non-standard treatment options with them, including opportunities for expanded access to unapproved, investigational drugs. Although our respondents had varying levels of understanding of expanded access programs, they seemed capable of making well-considered choices with regard to non-standard treatment options and had realistic expectations with regard to the safety and efficacy of such options. Dutch patients might be less likely to fall prey to false hope than often presumed.


2018 ◽  
Vol 14 (2) ◽  
pp. 76
Author(s):  
Emerson Y Chen ◽  
Charles D Lopez ◽  
Gina M Vaccaro ◽  
◽  
◽  
...  

Oncology drug development has recently introduced new systemic treatment options for hepatocellular carcinoma (HCC). Here we consider the general approaches to diagnostic workup, staging, and overall management of HCC with emphasis on systemic treatment options based on recent phase III clinical trials. Novel drug targets involving immunotherapy may change how we treat HCC in the near future.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8542-8542 ◽  
Author(s):  
Taymeyah E. Al-Toubah ◽  
Brian Morse ◽  
Jonathan R. Strosberg

8542 Background: Patients with advanced lung neuroendocrine neoplasms (NENs) have few treatment options. Capecitabine and temozolomide have recently showed significant activity in patients with pancreatic NETs, but data in lung NETs are limited. Methods: We retrospectively reviewed the records of patients treated at a large NET referral center to identify patients seen between 1/2008 and 9/2018 with metastatic lung NENs who received treatment with capecitabine and temozolomide (CAPTEM). Patients who were not seen at the center within the first month of treatment were excluded. Small cell lung cancer patients were also excluded. The primary endpoint was overall response rate per RECIST 1.1. Secondary endpoints included progression free survival, overall survival, and toxicity. Results: 20 patients were identified who received treatment with capecitabine/temozolomide. 14 (70%) were typical lung NETs, 5 (25%) atypical carcinoids, and 1 (5%) was defined as a large cell neuroendocrine carcinoma. 6 patients (30%) exhibited a best response of PR per RECIST 1.1 criteria, 11 (55%) SD, and 2 (10%) PD. 1 patient died 2 months after starting treatment. 11 eventually progressed (radiographically or clinically), only 6 of whom exhibited progression per RECIST 1.1 criteria. Median PFS was 11 months (95% CI, 6 – 16 months). Median OS was 68 months (95% CI, 35 – 101 months). Toxicity profile was mild with mainly grade 1, expected toxicities. 6 patients required dose reduction due to toxicity (2 for diarrhea and nausea, 1 for hand foot syndrome, 3 for thrombocytopenia). Conclusions: We identified a group of patients with metastatic lung NENs who received treatment with the CAPTEM regimen and exhibited a favorable response rate to treatment with a relatively tolerable toxicity profile. This regimen warrants further exploration in a prospective clinical trial.


2020 ◽  
Vol 55 (2) ◽  
pp. 216-221
Author(s):  
Colton H. Funkhouser ◽  
Kathleen M. Coerdt ◽  
Wasim Haidari ◽  
Michael A. Cardis

Objective: Hydrogen peroxide 40% (HP40) was approved by the US Food and Drug Administration for topical treatment of seborrheic keratosis (SK) in December 2017. This article will review phase II and III clinical trials to assess the drug’s efficacy, safety, and clinical application. Data Sources: A systematic literature review was performed using the terms “Eskata AND seborrheic keratosis,” and “hydrogen peroxide AND seborrheic keratosis” in the OVID MEDLINE, PubMed, Cochrane Library, EMBASE, and Web of Science databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. Study Selection and Data Abstraction: Articles written in English between January 2000 and mid-June 2020 discussing phase II and phase III clinical trials were evaluated. Data Synthesis: In 2 phase III clinical trials, 4% and 8% of patients treated with HP40 had a Physician Lesion Assessment score of zero for all 4 SKs, respectively, compared with 0% in both vehicle groups at the primary end point of day 106 ( P < 0.01; P < 0.0001). Relevance to Patient Care and Clinical Practice: HP40, although less effective, has a better safety profile than other treatment options. It should be especially considered for treatment of facial SKs, where it is most efficacious and where other treatment modalities, such as cryotherapy, are more challenging. Conclusions: HP40 is a new, safe alternative treatment for SKs, although it is expensive and only modestly effective, both of which somewhat limit its overall utility. HP40 is a promising topical alternative, particularly for cosmetically sensitive locations, such as the face.


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1834 ◽  
Author(s):  
Bartosz Puła ◽  
Aleksandra Gołos ◽  
Patryk Górniak ◽  
Krzysztof Jamroziak

Ibrutinib is the first Bruton’s tyrosine kinase (BTK) inhibitor, which showed significant clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients regardless of cytogenetic risk factors. Recent results of phase III clinical trials in treatment-naïve CLL patients shift the importance of the agent to frontline therapy. Nevertheless, beside its clinical efficacy, ibrutinib possesses some off-target activity resulting in ibrutinib-characteristic adverse events including bleeding diathesis and arrhythmias. Furthermore, acquired and primary resistance to the drug have been described. As the use of ibrutinib in clinical practice increases, the problem of resistance is becoming apparent, and new methods of overcoming this clinical problem arise. In this review, we summarize the mechanisms of BTK inhibitors’ resistance and discuss the post-ibrutinib treatment options.


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