scholarly journals The Impact of Immunological Checkpoint Inhibitors and Targeted Therapy on Chronic Pruritus in Cancer Patients

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 2
Author(s):  
Alessandro Allegra ◽  
Eleonora Di Salvo ◽  
Marco Casciaro ◽  
Caterina Musolino ◽  
Giovanni Pioggia ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Treatment Effectiveness ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Skin Toxicity ◽  
New Drugs ◽  
Cutaneous Toxicity ◽  
Chronic Pruritus ◽  
The Impact

Although pruritus may sometimes be a consequential situation to neoplasms, it more frequently emerges after commencing chemotherapy. In this review, we present our analysis of the chemotherapy treatments that most often induce skin changes and itching. After discussing conventional chemotherapies capable of inducing pruritus, we present our evaluation of new drugs such as immunological checkpoint inhibitors (ICIs), tyrosine kinase inhibitors, and monoclonal antibodies. Although ICIs and targeted therapy are thought to damage tumor cells, these therapies can modify homeostatic events of the epidermis and dermis, causing the occurrence of cutaneous toxicities in treated subjects. In the face of greater efficacy, greater skin toxicity has been reported for most of these drugs. A remarkable aspect of some reports is the presence of a probable correlation between cutaneous toxicity and treatment effectiveness in tumor patients who were treated with novel drugs such as nivolumab or pembrolizumab. Findings from these experiments demonstrate that the occurrence of any grade of skin side effects can be considered as a predictor of a better outcome. In the near future, studies on the relationship between the onset of skin alterations and outcomes could open new perspectives on the treatment of neoplasms through specific target therapy.

scholarly journals Efficacy and Safety of Modified Huang-Lian-Jie-Du Decoction Cream on Cancer Patients with Skin Side Effects Caused by EGFR Inhibition

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1081
Author(s):  
Ming-Yang Lee ◽  
Mei-Yi Lin ◽  
Yu-Ju Chang ◽  
Yu-Ting Tseng ◽  
I-An Huang ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Target Therapy ◽  
Herbal Medicines ◽  
Skin Toxicity ◽  
Dry Skin ◽  
Egfr Inhibition ◽  
The Mean ◽  
Skin Conditions

(1) Background: The epidermal growth factor inhibitors (EGFRIs)/tyrosine kinase inhibitors (TKIs) are effective for cancer target therapy, but acneiform rashes or so-called inflammatory papulopustular exanthemas are common (50% to 90%). The conventional therapy for EGFRIs/TKIs-induced skin toxicity is steroids and antibacterial drugs, but it is still ineffective for some patients, and EGFRIs/TKIs dose reduction/interruption may be needed. In this study, a modified Chinese herbal medicine, Huang-Lian-Jie-Du decoction cream with Yin-Cold (YC) medicine characteristic, was investigated for the effect on patients suffering EGFRIs/TKIs-induced skin toxicity. (2) Methods: The modified Huang-Lian-Jie-Du (mHLJD) decoction cream was made from 10 herbal medicines, including 4 major medicines (Huanglian, Huangqin, Huangbo, and Zhizi) in traditional HLJD decoction. Patients with EGFRIs/TKIs-induced skin toxicity were enrolled. Patients were excluded if they also used other cream for skin toxicity. Skin conditions were monitored by follow up every 2 weeks. The patients’ characteristics, the skin toxicities, treatment response, and adverse events were recorded and analyzed until skin problems resolved or the study ended. (3) Results: The mHLJD decoction cream and its sub-packages were stored at 4 °C before use. Thirty-four patients who had grade 1–3 skin toxicities after receiving EGFRIs/TKIs were enrolled. Seven patients withdrew or were excluded. Finally, data from 27 patients were analyzed. The mean grade of rash acneiform was significantly decreased from 2.19 (ranged 1 to 3) to 0.88 (ranged 0 to 2) after mHLJD decoction cream treatment for 4 weeks and to 0.55 (ranged 0 to 2) after mHLJD decoction cream treatment for 8 weeks. Additionally, the mean grade of dry skin was also significantly decreased from 1.57 (ranged 1 to 2) to 0.71 (ranged 0 to 1) after mHLJD decoction cream treatment for 4 weeks. The changes of skin toxicity were significant, with no obvious adverse events. (4) Conclusions: In summary, the mHLJD decoction cream provides benefits for alleviation of EGFRIs/TKIs-induced skin rash acneiform and dry skin. Additionally, no obvious side effects were found in patients using mHLJD decoction cream.

scholarly journals Case Report: Rechallenge With BRAF and MEK Inhibitors in Metastatic Melanoma: A Further Therapeutic Option in Salvage Setting?

2021 ◽  
Vol 11 ◽  
Author(s):  
Anna Stagno ◽  
Sabrina Vari ◽  
Alessio Annovazzi ◽  
Vincenzo Anelli ◽  
Michelangelo Russillo ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Clinical Benefit ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Option ◽  
Local Treatment ◽  
Standard Of Care ◽  
Serum Levels ◽  
High Serum ◽  
Mek Inhibitors

BackgroundThe combination of BRAF and MEK inhibitors represents the standard of care treatment for patients with metastatic BRAF-mutated melanoma, notwithstanding the high frequency of emergent resistance. Moreover, therapeutic options outside clinical trials are scarce when patients have progressed after both targeted therapy and therapy with immune checkpoint inhibitors. In this article, we report our experience with targeted therapy rechallenging with BRAF and MEK inhibitors in patients with metastatic BRAF-mutated melanoma after progression with kinase inhibitors and immunotherapy.MethodsFour patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF and MEK inhibitors after progression with targeted therapy and subsequent immunotherapy (checkpoint inhibitors).ResultsTwo patients (one of them was heavily pretreated) had partial response over 36 months (with local treatment on oligoprogression disease) and 10 months, respectively. A third patient with multisite visceral disease and high serum levels of lactate dehydrogenase had a short-lived clinical benefit rapidly followed by massive progression of disease (early progressor). The fourth patient, currently on treatment with BRAF/MEK inhibitors, is showing a clinical benefit and radiological stable disease over 3 months of therapy. Adverse events were manageable, similar to those reported during the first targeted therapy; the treatment was better tolerated at rechallenge compared with the first treatment by two out of four patients.

scholarly journals Immune Checkpoint Inhibitors as Monotherapy or Within a Combinatorial Strategy in Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 21 (17) ◽  
pp. 6302
Author(s):  
Michela Guardascione ◽  
Giuseppe Toffoli
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Antiangiogenic Agents ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

In advanced-stage hepatocellular carcinoma (HCC), systemic treatment represents the standard therapy. Target therapy has marked a new era based on a greater knowledge of molecular disease signaling. Nonetheless, survival outcomes and long-term response remain unsatisfactory, mostly because of the onset of primary or acquired resistance. More recently, results from clinical trials with immune targeting agents, such as the immune checkpoint inhibitors (ICIs), have shown a promising role for these drugs in the treatment of advanced HCC. In the context of an intrinsic tolerogenic liver environment, since HCC-induced immune tolerance, it is supported by multiple immunosuppressive mechanisms and several clinical trials are now underway to evaluate ICI-based combinations, including their associations with antiangiogenic agents or multikinase kinase inhibitors and multiple ICIs combinations. In this review, we will first discuss the basic principles of hepatic immunogenic tolerance and the evasive mechanism of antitumor immunity in HCC; furthermore we will elucidate the consistent biological rationale for immunotherapy in HCC even in the presence of an intrinsic tolerogenic environment. Subsequently, we will critically report and discuss current literature on ICIs in the treatment of advanced HCC, including a focus on the currently explored combinatorial strategies and their rationales. Finally, we will consider both challenges and future directions in this field.

The Role of Target Therapy in the Treatment of Gastrointestinal Noncolorectal Cancers: Clinical Impact and Cost Consideration

2018 ◽  
Vol 18 (5) ◽  
pp. 430-441 ◽  
Author(s):  
Massimiliano Berretta ◽  
Carmela Romano ◽  
Raffaele Di Francia ◽  
Chiara De Diviitis ◽  
Vincenzo Canzonieri ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Multidisciplinary Approach ◽  
Kinase Inhibitors ◽  
Target Therapy ◽  
New Drugs ◽  
Treatment Modalities ◽  
New Treatment ◽  
Remarkable Progress ◽  
Egfr Antibody

Gastrointestinal (GI) tumors are among the leading cause of death in cancer patients worldwide. Particularly, gastric cancer (GC) is the third cause of cancer deaths, whereas esophageal neoplasm is the eighth leading most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increasing. Also, Hepatocellular carcinoma, Cholangiocarcinoma and pancreatic cancer represent a very interesting model to multidisciplinary approach and recently new drugs are used in their treatment. Currently, new clinical trials are designed including classic chemotherapy in association with either small molecule inhibitors (i.e. Tyrosine Kinase inhibitors) and/or monoclonal antibody (i.e. anti-EGFR antibody). Moreover, a comprehensive list of new molecules for target therapy is included in this issue. The development of new treatment modalities (multidisciplinary approach) and targeted therapy approaches have contributed to improving the outcome in these cancer diseases. During the past few years, remarkable progress in molecular biology of malignancy, the discovery of specific targets, and the resulting development of systemic drugs that block critical kinases and several molecular pathways have all contributed to progress in cancer treatment, also in GI non-colorectal cancer treatment.

Meta-analysis of outcomes of VEGF and EGFR targeted biologic therapy in relapsed metastatic colorectal cancer (mCRC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 534-534 ◽  
Author(s):  
David Chan ◽  
Eva Segelov ◽  
Jeremy David Shapiro ◽  
Timothy Jay Price ◽  
Christos Stelios Karapetis ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Biologic Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Biologic Agents ◽  
First Line ◽  
Grade 3 ◽  
Line Setting ◽  
The Impact

534 Background: Biologic therapies used in treatment of mCRC are expensive and there is debate about their value. We examined the impact of biologic therapy on overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 toxicity for patients beyond first-line treatment. Methods: MEDLINE, EMBASE, and Cochrane libraries were searched for randomized studies in relapsed mCRC comparing treatment containing targeted therapy to the same treatment without targeted therapy. Biologic agents were classed as: EGFR-inhibitors (EGFR-I), VEGF antibody/trap and VEGFR tyrosine kinase inhibitors (TKI). Only KRAS wild-type patients were included for EGFR-I analysis. Results were aggregated according to standard meta-analytic techniques. Results: 10 studies evaluating 5,847 patients were identified. Considering subgroups and lines, OS and PFS benefit was demonstrated in all groups across all lines except for OS in 2nd line EGFR-I use (which may be due to subsequent crossover). A benefit to ORR was seen with EGFR-I 2nd line (Pooled ORR benefit +24%, Odds Ratio (OR) 4.44, 95% CI 3.20-6.18), EGFR-I 3rd line and beyond (Pooled ORR benefit +16%), VEGF antibody/trap (Pooled ORR benefit +7.2%, OR 2.00, 95% CI 1.57-2.54) and VEGFR TKI (Pooled ORR benefit +1.9%, OR 2.05, 95% CI 1.27-3.30). The risk of grade 3/4 toxicity was greater with the addition of all targeted agents. Conclusions: The use of VEGF and EGFR targeted biologic agents beyond first-line setting in mCRC results in a benefit to OS, PFS and ORR for all agents except for OS benefit with second-line EGFR-I. This benefit comes at the cost of increased toxicity. [Table: see text]

Analysis of real-world data (RWD) on treatment (tx) sequencing in patients with advanced non-small cell lung cancer (aNSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20642-e20642
Author(s):  
Meng Ma ◽  
Xiang Zhou ◽  
Howard Goldsweig ◽  
Nicholas Hahner ◽  
Dianwei Han ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Rank Test ◽  
Real World Data ◽  
Therapeutic Modalities ◽  
Platinum Based Chemotherapy ◽  
Line Of Therapy ◽  
Line Setting

e20642 Background: While optimal sequencing of systemic therapy in aNSCLC is critical to achieve maximal clinical benefit, it is practically challenging to study tx sequencing through clinical trials. RWD allow retrospective, observational studies to examine tx patterns and associated clinical outcomes. Methods: 1,609 aNSCLC patients who received systemic therapies at Mount Sinai hospitals were analyzed for the number of line of therapy (LOT), therapeutic modalities (chemotherapy, targeted therapy and immunotherapy), and the sequence in which treatments were given when LOT > 1. Time to tx discontinuation (TTD) was used as a surrogate clinical endpoint for outcomes. Results: 578 of the 1,609 (36%) patients received more than one LOT. 356 (22%) received tyrosine kinase inhibitors (TKIs), and 297 (16%) received immune checkpoint inhibitors (CPIs). Kaplan-Meier analysis revealed that among 297 patients who received CPIs, median TTD was longer in the 1st line setting (295 days, 95% CI 169 to 523; n=132) than when LOT > 1 (169 days, 95% CI 113 to 269; n=165), although the difference was not statistically significant (P=0.092, log-rank test). No difference of TTD on TKIs was observed between LOT = 1 and LOT > 1 (P=0.51). With respect to tx sequencing, when patients (n=94) received TKIs as the 1st LOT, 60%, 35%, and 5% of them received another TKI, chemotherapy, or a CPI-containing regimen, respectively, as the 2nd LOT. Among patients (n=370) who progressed on 1st line platinum-based chemotherapy, 52%, 32%, and 16% received another chemo regimen, a CPI-containing regimen, or a targeted therapy, respectively, as the 2nd LOT; these percentages shifted significantly toward more CPIs (24%, 66%, 10% for chemo, CPI, targeted, respectively) when only 2016-2018 data were examined. In the 2nd line setting after platinum therapy, TTD was significantly longer in the CPI group (332 days, 95% CI 169-484) compared to the chemo group (88 days, 95% CI 65-100; P<0.0001), consistent with results from pivotal clinical trials. Conclusions: As the tx algorithm of aNSCLC has been evolving rapidly, we observed diverse tx patterns in RWD. Various tx sequences may impact patient outcomes, and therefore warrant further investigation.

scholarly journals Some aspects of nivolumab administration in treatment for metastatic melanoma (clinical cases)

2021 ◽  
pp. 64-74
Author(s):  
L. Yu. Vladimirova ◽  
A. Eh. Storozhakova ◽  
I. L. Popova ◽  
S. N. Kabanov ◽  
N. A. Abramova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Complete Regression ◽  
Cutaneous Toxicity ◽  
First Case

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria  for  most clinical trials do not envisage recruiting such patients. The  immune-mediated toxicity of  immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The  first case is of  interest due to the  presence of  brain  metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

scholarly journals The Impact of Variant Allele Frequency in EGFR Mutated NSCLC Patients on Targeted Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Alex Friedlaender ◽  
Petros Tsantoulis ◽  
Mathieu Chevallier ◽  
Claudio De Vito ◽  
Alfredo Addeo
Keyword(s):  
Targeted Therapy ◽  
Allele Frequency ◽  
Kinase Inhibitors ◽  
Survival Rates ◽  
Allelic Frequency ◽  
Exact Estimate ◽  
Egfr Mutations ◽  
Tumor Evolution ◽  
Cancer Evolution ◽  
The Impact

EGFR mutations represent the most common currently targetable oncogenic driver in non-small cell lung cancer. There has been tremendous progress in targeting this alteration over the course of the last decade, and third generation tyrosine kinase inhibitors offer previously unseen survival rates among these patients. Nonetheless, a better understanding is still needed, as roughly a third of patients do not respond to targeted therapy and there is an important heterogeneity among responders. Allelic frequency, or the variant EGFR allele frequency, corresponds to the fraction of sequencing reads harboring the mutation. The allelic fraction is influenced by the proportion of tumor cells in the sample, the presence of copy number alterations but also, most importantly, by the proportion of cells within the tumor that carry the mutation. Mutations that occur early in tumor evolution, often called clonal or truncal, have a higher allelic frequency than late, subclonal mutations, and are more often drivers of cancer evolution and attractive therapeutic targets. Most, but not all, EGFR mutations are clonal. Although an exact estimate of clonal proportion is hard to derive computationally, the allelic frequency is readily available to clinicians and could be a useful surrogate. We hypothesized that tumors with low allelic frequency of the EGFR mutation will respond less favorably to targeted treatment.

scholarly journals Survey of the Impact of COVID-19 on Oncologists’ Decision Making in Cancer

2020 ◽  
pp. 1248-1257 ◽  
Author(s):  
Yüksel Ürün ◽  
Syed A. Hussain ◽  
Ziad Bakouny ◽  
Daniel Castellano ◽  
Saadettin Kılıçkap ◽  
...  
Keyword(s):  
Decision Making ◽  
Metastatic Disease ◽  
Online Survey ◽  
Kinase Inhibitors ◽  
Clinical Decision Making ◽  
Checkpoint Inhibitors ◽  
Clinical Decision ◽  
Immune Therapies ◽  
Novel Coronavirus ◽  
The Impact

PURPOSE To understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision making was influenced by the pandemic. METHODS An online survey was conducted between March 24 and April 29, 2020. RESULTS A total of 343 oncologists from 28 countries participated. The median age was 43 years (range, 29-68 years), and the majority were male (62%). At the time of the survey, nearly all participants self-reported an outbreak in their country (99.7%). Personal protective equipment was available to all participants, of which surgical mask was the most common (n = 308; 90%). Telemedicine, in the form of phone or video encounters, was common and implemented by 80% (n = 273). Testing patients with cancer for COVID-19 via reverse transcriptase polymerase chain reaction before systemic treatment was not routinely implemented: 58% reported no routine testing, 39% performed testing in selected patients, and 3% performed systematic testing in all patients. The most significant factors influencing an oncologist’s decision making regarding choice of systemic therapy included patient age and comorbidities (81% and 92%, respectively). Although hormonal treatments and tyrosine kinase inhibitors were considered to be relatively safe, cytotoxic chemotherapy and immune therapies were perceived as being less safe or unsafe by participants. The vast majority of participants stated that during the pandemic they would use less chemotherapy, immune checkpoint inhibitors, and steroids. Although treatment in neoadjuvant, adjuvant, and first-line metastatic disease was less affected, most of the participants stated that they would be more hesitant to recommend second- or third-line therapies in metastatic disease. CONCLUSION Decision making by oncologists has been significantly influenced by the ongoing COVID-19 pandemic.

scholarly journals Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chau Yee Ng ◽  
Chun-Bing Chen ◽  
Ming-Ying Wu ◽  
Jennifer Wu ◽  
Chih-Hsun Yang ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Anticancer Drugs ◽  
Target Therapy ◽  
Drug Hypersensitivity ◽  
Skin Toxicity ◽  
Stevens Johnson Syndrome ◽  
Drug Reactions ◽  
Skin Reactions ◽  
Inappropriate Use ◽  
Cutaneous Drug Reactions

Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

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