Back from the brink: EGFR inhibition in gastroesophageal cancer

2021 ◽  
pp. clincanres.0533.2021
Author(s):  
Mark R Openshaw ◽  
David J Pinato ◽  
Nicola Valeri
Keyword(s):  
Gastroesophageal Cancer ◽  
Egfr Inhibition

SIMULTANEOUS ESOPHAGO-GASTRECTOMY WITH COLONIC INTERPOSITION AS A METHOD OF SURGICAL TREATMENT OF GASTROESOPHAGEAL CANCER WITH HIGH INVOLVEMENT OF THE ESOPHAGUS

2017 ◽  
Vol 63 (1) ◽  
pp. 146-152
Author(s):  
Mikhail Ter-ovanesov ◽  
Aleksandr Levitskiy ◽  
E. Lesnidze ◽  
Aram Gaboyan ◽  
Mariya Kukosh ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Long Term Results ◽  
Esophageal Reconstruction ◽  
Gastroesophageal Cancer ◽  
Colonic Interposition ◽  
Simultaneous Application ◽  
High Involvement ◽  
Surgical Access ◽  
Critical Overview

In the current oncological practice surgical treatment of gastroesophageal cancer with high involvement of the esophagus can extend to total esophago-gastrectomy with colonic interposition as the main method of radical treatment. However the technical complexity and high risk of the intervention are factors in determining the divergent views on the operation itself, testimony for the criteria of patient’s selection, choice of surgical access and the formation of a colonic graft in conjunction with method of esophageal reconstruction. The long-term results of operative intervention depend primarily on the extent of tumor process but obviously higher than after conservative treatment. This article presents a brief critical overview of the main aspects of the simultaneous application of esophago-gastrectomy in surgery of gastroesophageal cancer with high esophageal involvement and our clinical case of successful surgical treatment of a woman with pregnancy-associated gastroesophageal cancer.

Optimising Chemotherapy for Frail and Older Patients With Advanced Gastroesophageal Cancer: The GO2 Phase III Trial

2020 ◽  
Author(s):  
Peter Hall ◽  
Daniel Swinson ◽  
David A. Cairns ◽  
Justin Waters ◽  
Russell Petty ◽  
...  
Keyword(s):  
Older Patients ◽  
Phase Iii ◽  
Gastroesophageal Cancer ◽  
Phase Iii Trial

Recent Advances on Epidermal Growth Factor Receptor as a Molecular Target for Breast Cancer Therapeutics

2020 ◽  
Vol 21 ◽  
Author(s):  
Swathi R. Shetty ◽  
Ragini Yeeravalli ◽  
Tanya Bera ◽  
Amitava Das
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Type I ◽  
Egfr Inhibition ◽  
Epidermal Growth

: Epidermal growth factor receptor (EGFR), a type-I transmembrane protein with intrinsic tyrosine kinase activity is activated by peptide growth factors such as EGF, epigen, amphiregulin, etc. EGFR plays a vital role in regulating cell growth, migration, and differentiation in various tissue-specific cancers. It has been reported to be overexpressed in lung, head, and neck, colon, brain, pancreatic, and breast cancer that trigger tumor progression and drug resistance. EGFR overexpression alters the signaling pathway and induces cell division, invasion, and cell survival. Our prior studies demonstrated that EGFR inhibition modulates chemosensitivity in breast cancer stem cells thereby serving as a potential drug target for breast cancer mitigation. Tyrosine kinase inhibitors (Lapatinib, Neratinib) and monoclonal antibodies (Trastuzumab) targeting EGFR have been developed and approved by the US FDA for clinical use against breast cancer. This review highlights the critical role of EGFR in breast cancer progression and enumerates the various approaches being undertaken to inhibit aggressive breast cancers by suppressing the downstream pathways. Further, the mechanisms of action of potential molecules at various stages of drug development as well as clinically approved drugs for breast cancer treatment are illustrated.

scholarly journals Gender Differences in Treatment Allocation and Survival of Advanced Gastroesophageal Cancer: a Population-Based Study

2021 ◽  
Author(s):  
Willemieke P M Dijksterhuis ◽  
Marianne C Kalff ◽  
Anna D Wagner ◽  
Rob H A Verhoeven ◽  
Valery E P P Lemmens ◽  
...  
Keyword(s):  
Gender Differences ◽  
Systemic Treatment ◽  
Statistical Tests ◽  
Tumor Biology ◽  
Rank Test ◽  
Lower Probability ◽  
Gastroesophageal Cancer ◽  
Treatment Allocation ◽  
Netherlands Cancer Registry ◽  
Treatment Administration

Abstract Background Biological sex and gender have been reported to impact incidence and overall survival (OS) of curatively treated gastroesophageal cancer. The aim of this study was to compare palliative treatment allocation and OS between women and men with advanced gastroesophageal cancer. Methods Patients with an unresectable (cT4b) or metastatic (cM1) esophageal (including cardia) adenocarcinoma (EAC) or squamous cell carcinoma (ESCC), or gastric adenocarcinoma (GAC) diagnosed in 2015-2018 were identified in the Netherlands Cancer Registry. Treatment allocation was compared using chi-squared tests and multivariable logistic regression analyses, and OS using the Kaplan-Meier method with log-rank test and Cox proportional hazard analysis. All statistical tests were 2-sided. Results Of patients with EAC (n = 3,077), ESCC (n = 794) and GAC (n = 1,836), 18.0%, 39.4% and 39.1% were women, respectively. Women received less often systemic treatment compared to men in EAC (42.7% vs. 47.4%, P = 0.045) and GAC (33.8% vs. 38.8%, P = 0.03), but not in ESCC (33.2% vs. 39.5%, P = 0.07). Women had a lower probability of receiving systemic treatment in GAC in multivariable analyses (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.62-1.00), but not in EAC (OR = 0.86, 95%CI = 0.69-1.06) and ESCC (OR = 0.81, 95%CI = 0.57-1.14). Median OS was lower in women with EAC (4.4 vs. 5.2 months, P = 0.04), but did not differ after adjustment for patient and tumor characteristics and systemic treatment administration. Conclusion We observed statistically significant and clinically relevant gender differences in systemic treatment administration and OS in advanced gastroesophageal cancer. Causes of these disparities may be sex-based, i.e. related to tumor biology, as well as gender-based, e.g. related to differences in treatment choices.

scholarly journals Immunotherapy Predictive Molecular Markers in Advanced Gastroesophageal Cancer: MSI and Beyond

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1715
Author(s):  
Robin Park ◽  
Laercio Lopes ◽  
Anwaar Saeed
Keyword(s):  
Treatment Options ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Gastroesophageal Cancer ◽  
Programmed Death ◽  
Phase Iii Trials ◽  
Tumor Mutational Burden ◽  
Large Phase ◽  
Programmed Death 1

Advanced gastroesophageal cancer (GEC) has a poor prognosis and limited treatment options. Immunotherapy including the anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab have been approved for use in various treatment settings in GEC. Additionally, frontline chemoimmunotherapy regimens have recently demonstrated promising efficacy in large phase III trials and have the potential to be added to the therapeutic armamentarium in the near future. There are currently several immunotherapy biomarkers that are validated for use in the clinical setting for GEC including programmed death ligand-1 (PD-L1) expression as well as the tumor agnostic biomarkers such as mismatch repair or microsatellite instability (MMR/MSI) and tumor mutational burden (TMB). However, apart from MMR/MSI, these biomarkers are imperfect because none are highly sensitive nor specific. Therefore, there is an unmet need for immunotherapy biomarker development. To this end, several biomarkers are currently being evaluated in ongoing trials with some showing promising predictive potential. Here, we summarize the landscape of immunotherapy predictive biomarkers that are currently being evaluated in GEC.

scholarly journals An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Erica M. Stringer-Reasor ◽  
Jori E. May ◽  
Eva Olariu ◽  
Valerie Caterinicchia ◽  
Yufeng Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Repair ◽  
Pilot Study ◽  
Expression Analysis ◽  
Triple Negative Breast Cancer ◽  
Gene Expression Analysis ◽  
Triple Negative ◽  
Egfr Inhibition ◽  
Link Type

Abstract Background Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Methods A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded. Results Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0–2). Fifty percent of patients were Caucasian, 45% African–American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug–drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed. Trial registration ClinicalTrials.gov, NCT02158507. Registered on 12 September 2014

Influence of Baseline Positron Emission Tomography in Metastatic Gastroesophageal Cancer on Survival and Response to Therapy

Oncology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Ahmed Abdelhakeem ◽  
Madhavi Patnana ◽  
Xuemei Wang ◽  
Jane E. Rogers ◽  
Mariela Blum Murphy ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Response To Therapy ◽  
Emission Tomography ◽  
Gastroesophageal Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Positron Emission ◽  
Pet Ct ◽  
Metastatic Burden

<b><i>Background:</i></b> The value of baseline fluorodeoxyglucose-positron emission tomography-computed tomography (PET-CT) remains uncertain once gastroesophageal cancer is metastatic. We hypothesized that assessment of detailed PET-CT parameters (maximum standardized uptake value [SUVmax] and/or total lesion glycolysis [TLG]), and the extent of metastatic burden could aid prediction of probability of response or prognosticate. <b><i>Methods:</i></b> We retrospectively analyzed treatment-naive patients with stage 4 gastroesophageal cancer (December 2002–August 2017) who had initial PET-CT for cancer staging at MD Anderson Cancer Center. SUVmax and TLG were compared with treatment outcomes for the full cohort and subgroups based on metastatic burden (≤2 or &#x3e;2 metastatic sites). <b><i>Results:</i></b> We identified 129 patients with metastatic gastroesophageal cancer who underwent PET-CT before first-line therapy. The median follow-up time was 61 months. The median overall survival (OS) was 18.5 months; the first progression-free survival (PFS) was 5.5 months. SUVmax or TLG of the primary tumor or of all metastases combined had no influence on OS or PFS, whether the number of metastases was ≤2 or &#x3e;2. Overall response rates (ORRs) to first-line therapy were 48% and 45% for patients with ≤2 and &#x3e;2 metastases, respectively (nonsignificant). ORR did not differ based on low or high values of SUVmax or TLG. <b><i>Conclusions:</i></b> This is the first assessment of a unique set of PET-CT data and its association with outcomes in metastatic gastroesophageal cancer. In our large cohort of patients, detailed analyses of PET-CT (by SUVmax and/or TLG) did not discriminate any parameters examined. Thus, baseline PET-CT in untreated metastatic gastroesophageal cancer patients has limited or no utility.

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.

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