scholarly journals Hitting the Right Spot: Advances in the Treatment of NSCLC With Uncommon EGFR Mutations

2021 ◽  
Vol 19 (Suppl_2) ◽  
pp. S1-S11
Author(s):  
Joshua K. Sabari ◽  
John V. Heymach ◽  
Beth Sandy
Keyword(s):  
Targeted Therapy ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Patient Specific ◽  
Molecular Testing ◽  
Development Of Resistance ◽  
Treatment Plans ◽  
The Right ◽  
Selection Of

An understanding of the biology of uncommon epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) is evolving. These mutations are important for the selection of targeted therapy and the development of resistance. The advent of genomic profiling has led to guideline-recommended molecular testing to identify patients with NSCLC who carry uncommon EGFR mutations to aid in the selection of appropriate targeted therapy. This article discusses the efficacy and safety of current and emerging targeted therapies for the treatment of uncommon EGFR mutations in NSCLC to aid in developing patient-specific treatment plans.

Re-use of erlotinib in a patient using osimertinib after erlotinib, case report

2021 ◽  
pp. 107815522110191
Author(s):  
Pinar Gursoy
Keyword(s):  
Lung Cancer ◽  
Case Report ◽  
Treatment Options ◽  
Resistance Mutation ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Egfr Mutations ◽  
T790m Mutation ◽  
Development Of Resistance ◽  
Exon 19

Introduction Most patients with non-small-cell lung cancer tumors that have epidermal growth factor receptor (EGFR) mutations have deletion mutations in exon 19 or exon 21, or both.In recent years, targeted therapies in lung cancer have increased survival, but the development of resistance to these drugs poses a major problem. Thesubstitution of methionineforthreonine at position 790 (T790M) mutation,is primarily responsible for this resistance. However, after osimertinib used in T790M positivepatients treatment options are generally limited to chemotherapy. Case report We reported the efficacy of erlotinib, which we reapplied due to the disappearance of the resistance mutation after osimertinib in a 68-year-old patient using osimertinib after erlotinib. Management and outcome: In the patient using erlotinib due to exon 19 deletion when progression was observed and T790M positivity was detected, osimertinib treatment was initiated. However, when T790M was found to be negative with rebiopsy in progression after osimertinib, a complete response was achieved by restarting erlotinib. Discussion The strategy of restarting erlotinib treatment with negative T790M mutation detected in biopsies of patients with osimertinib resistance may be an acceptable treatment option.

scholarly journals Towards integration of 64Cu-DOTA-trastuzumab PET-CT and MRI with mathematical modeling to predict response to neoadjuvant therapy in HER2 + breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Angela M. Jarrett ◽  
David A. Hormuth ◽  
Vikram Adhikarla ◽  
Prativa Sahoo ◽  
Daniel Abler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Treatment Response ◽  
Growth Factor Receptor ◽  
Patient Specific ◽  
Mathematical Framework ◽  
Breast Cancer Patients ◽  
Data Types ◽  
Her2 Breast Cancer ◽  
Mri Scans

AbstractWhile targeted therapies exist for human epidermal growth factor receptor 2 positive (HER2 +) breast cancer, HER2 + patients do not always respond to therapy. We present the results of utilizing a biophysical mathematical model to predict tumor response for two HER2 + breast cancer patients treated with the same therapeutic regimen but who achieved different treatment outcomes. Quantitative data from magnetic resonance imaging (MRI) and 64Cu-DOTA-trastuzumab positron emission tomography (PET) are used to estimate tumor density, perfusion, and distribution of HER2-targeted antibodies for each individual patient. MRI and PET data are collected prior to therapy, and follow-up MRI scans are acquired at a midpoint in therapy. Given these data types, we align the data sets to a common image space to enable model calibration. Once the model is parameterized with these data, we forecast treatment response with and without HER2-targeted therapy. By incorporating targeted therapy into the model, the resulting predictions are able to distinguish between the two different patient responses, increasing the difference in tumor volume change between the two patients by > 40%. This work provides a proof-of-concept strategy for processing and integrating PET and MRI modalities into a predictive, clinical-mathematical framework to provide patient-specific predictions of HER2 + treatment response.

Immunohistochemistry Profile Predicts EGFR Mutation Status in Lung Adenocarcinoma

2020 ◽  
Vol 28 (5) ◽  
pp. 502-506
Author(s):  
Wencheng Li ◽  
Angela G. Niehaus ◽  
Stacey S. O’Neill
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Mutation Status ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Napsin A ◽  
Therapeutic Decisions

Significant advances in targeted therapy have been made in recent years for patients with lung adenocarcinoma. These targeted therapies have made molecular testing of paramount importance to drive therapeutic decisions. Material for testing is often limited, particularly in cytology specimens and small core biopsies. A reliable screening tool is invaluable in triaging limited tissue and selection for epidermal growth factor receptor ( EGFR) mutation testing. We hypothesized that the immunohistochemistry (IHC) profile of lung adenocarcinoma predicts EGFR mutation status. In this retrospective study, we evaluated the thyroid transcription factor-1 (TTF-1)/napsin A IHC profile and EGFR mutation status in 339 lung adenocarcinomas at our academic institution. In our cohort, we found that 92.3% of cases were positive for TTF-1 and/or napsin A by IHC with an EGFR positivity rate of 17.3%. Importantly, 7.7% of the cases were dual TTF-1/napsin A negative, and none of these cases contained EGFR mutations. This finding supports the use of TTF-1 and napsin A IHC to identify cases where EGFR mutation status will be negative, thus preserving limited tissue for other ancillary testing.

Lung Cancer in 2013: State of the Art Therapy for Metastatic Disease

2013 ◽  
pp. 339-346
Author(s):  
Frances A. Shepherd ◽  
Paul A. Bunn ◽  
Luis Paz-Ares
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Poor Performance ◽  
Initial Therapy ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Molecular Features ◽  
Platinum Doublet

Lung cancer is the leading worldwide cause of cancer death and the majority of patients present with metastatic stage IV disease. At diagnosis, clinical, histologic, and molecular features must be considered in therapeutic decision-making for systemic therapy. Molecular testing for at least epidermal growth factor receptor ( EGFR) and ALK should be performed in all patients before therapy. Platinum doublet chemotherapy may be considered for “fit” patients who do not have a molecular driver genetic abnormality. Bevacizumab can be considered for addition to the doublet in patients with nonsquamous cancers who have no contraindications. A pemetrexed combination is considered only in nonsquamous histology. Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance. The tyrosine-kinase inhibitors (TKIs) may be continued until multisite, symptomatic progression. For patients initially treated with a platinum doublet, maintenance chemotherapy with pemetrexed, erlotinib, gemcitabine, or possibly docetaxel is an option with selection based on clinical features, histology, type of initial therapy, and response to first-line therapy.

Molecular Profiling and the Reclassification of Cancer: Divide and Conquer

2013 ◽  
pp. 127-134 ◽  
Author(s):  
Javier Munoz ◽  
Charles Swanton ◽  
Razelle Kurzrock
Keyword(s):  
Growth Factor Receptor ◽  
Molecular Profiling ◽  
Small Cell ◽  
Divide And Conquer ◽  
Egfr Mutations ◽  
Diagnostic Process ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
The Right ◽  
Molecular Aberrations

Cancer is one of the leading causes of mortality in the world. Choosing the best treatment is dependent on making the right diagnosis. The diagnostic process has been based on light microscopy and the identification of the organ of tumor origin. Yet we now know that cancer is driven by molecular processes, and that these do not necessarily segregate by organ of origin. Fortunately, revolutionary changes in technology have enabled rapid genomic profiling. It is now apparent that neoplasms classified uniformly (e.g., non-small cell lung cancer) are actually comprised of up to 100 different molecular entities. For instance, tumors bearing ALK alterations make up about 4% of non-small cell lung cancers, and tumors bearing epidermal growth factor receptor (EGFR) mutations, approximately 5% to 10%. Importantly, matching patients to therapies targeted against their driver molecular aberrations has resulted in remarkable response rates. There is now a wealth of evidence supporting a divide-and-conquer strategy. Herein, we provide a concise primer on the current state-of-the-art of molecular profiling in the cancer clinic.

Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal Growth Factor Receptor 2 (HER2) –Negative and Adjuvant Targeted Therapy for HER2-Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline

2016 ◽  
Vol 34 (20) ◽  
pp. 2416-2427 ◽  
Author(s):  
Neelima Denduluri ◽  
Mark R. Somerfield ◽  
Andrea Eisen ◽  
Jamie N. Holloway ◽  
Arti Hurria ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Clinical Practice ◽  
Targeted Therapy ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
American Society ◽  
Selection Of

Purpose A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)–positive breast cancers was identified for adaptation. Methods The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability. Results On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members. Recommendations Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline- and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available.

scholarly journals 04. ASSESSMENT OF EFFICACY AND SAFETY OF OSIMERTINIB FOR PATIENTS WITH INTRACRANIAL METASTATIC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
Anders Erickson ◽  
Priscilla Brastianos ◽  
Sunit Das
Keyword(s):  
Targeted Therapy ◽  
Metastatic Disease ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Risk Of Bias ◽  
Egfr Mutations ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Egfr Mutant ◽  
Intracranial Metastatic Disease

Abstract INTRODUCTION Intracranial metastatic disease (IMD) is a serious and life-altering complication for many patients with cancer. Targeted therapy may address limitations of current treatments as an additional agent to achieve intracranial disease control in some patients with IMD. Osimertinib is a mutant epidermal growth factor receptor (EGFR) inhibitor that can penetrate the blood-brain barrier and inhibit tumor cell survival and proliferation in patients with non-small cell lung cancer (NSCLC) with specific EGFR mutations. The purpose of this study is to assess the efficacy and safety of osimertinib in the management of IMD. METHODS Studies reporting intracranial outcomes for patients with EGFR-mutant NSCLC and IMD treated with osimertinib were included. Among 271 records identified in MEDLINE and EMBASE, 15 studies fulfilled eligibility criteria. Outcomes were pooled using a random-effects model. Risk of bias was assessed using the Cochrane Risk of Bias tool and modified Newcastle-Ottawa scale. Information extracted included study characteristics, intracranial efficacy measures, and safety measures. Meta-analyses were conducted to pool applicable outcomes. RESULTS 15 studies reporting on 324 patients were included in the analysis. Combined CNS ORR and CNS DCR were calculated to be 64% (95% CI, 53–76%; n = 195), and 90% (95% CI, 85–93%; n = 246). Risk ratios for CNS ORR and CNS DCR were calculated to be 1.44 (95% CI, 1.06–1.96; n = 52) and 1.13 (95% CI, 0.96–1.33; n = 52). Included studies reported complete intracranial response rates of 7–23%, median best decrease in intracranial lesion size of 40–64%, and grade 3+ adverse event rates of 19–39%. CONCLUSIONS Findings reported here support a potential role for osimertinib for patients with EGFR-mutant NSCLC and IMD. Clinical decision-makers would benefit from the inclusion of patients with IMD in future trials to identify factors that predict responses to targeted therapy.

scholarly journals Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy inKRASWild-Type Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Tze-Kiong Er ◽  
Chih-Chieh Chen ◽  
Luis Bujanda ◽  
Marta Herreros-Villanueva
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Genetic Determinants ◽  
Secondary Resistance ◽  
Epidermal Growth ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Selection Of Patients ◽  
Selection Of

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit.KRASmutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction ofKRASwild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation ofBRAF,NRAS,PIK3CA, andPTENstatus could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

scholarly journals B7-H3-Induced Signaling in Lung Adenocarcinoma Cell Lines with Divergent Epidermal Growth Factor Receptor Mutation Patterns

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Meng Ding ◽  
Haixiu Liao ◽  
Nannan Zhou ◽  
Ying Yang ◽  
Shihe Guan ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Adenocarcinoma Cell ◽  
Epidermal Growth

The cosignal molecule B7-H3 is gaining attention due to its abnormal expression and abundant signal transduction in many types of malignancies. B7-H3-induced signaling includes at least three cascades: PI3K/AKT, JAK2/STAT3, and Raf/MEK/ERK1/2, which are also involved in epidermal growth factor receptor- (EGFR-) triggered signaling in lung adenocarcinoma cells. However, the correlation between B7-H3-induced signaling and EGFR signaling, and between B7-H3-targeted immunotherapy and EGFR-targeted therapy in lung adenocarcinoma, remains to be elucidated. Herein we find that knockout of B7-H3 gene decreased cell survival and increased EGFR-tyrosine kinase inhibitor gefitinib susceptibility of both H3255 and HCC827 cells, two lung adenocarcinoma cell lines harboring EGFR L858R (exon 21) and Del E746-A750 (exon 19) mutations, respectively. B7-H3 deletion resulted in dramatic reduction of phosphorylation level of AKT and STAT3 in H3255 cells while having mild-to-moderate suppression on AKT, STAT3, and ERK1/2 in HCC827 cells. Gefitinib had similar effects with B7-H3 deletion both in H3255 and HCC827 cells. Furthermore, B7-H3 ablation had significant synergistic effects with gefitinib in HCC827 cells. Collectively, our study reveals B7-H3-induced signaling in lung adenocarcinoma cell lines with divergent EGFR mutations, and a translational potential of combined targeted therapy of B7-H3 and EGFR in lung adenocarcinoma with EGFR Del E746-A750 mutation.

Targeted Therapy in Older Patients With Solid Tumors

2014 ◽  
Vol 32 (24) ◽  
pp. 2635-2646 ◽  
Author(s):  
Ciara M. Kelly ◽  
Derek G. Power ◽  
Stuart M. Lichtman
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Older Patients ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Patient Specific ◽  
Major Step ◽  
Epidermal Growth

The introduction of targeted therapy has ushered in the era of personalized medicine in cancer therapy. The increased understanding of tumor heterogeneity has led to the determination of specific targets that can be exploited in treatment. This review highlights approved drugs in different therapeutic classes, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, drugs targeted to the human epidermal growth factor receptor 2, BRAF-mutation targeted drugs, anti–epidermal growth factor receptor inhibitors, and anti-vascular endothelial growth factor therapy. There have not been elderly patient–specific trials of these therapies. Most of the data are extrapolated from larger trials in which older patients generally were a fraction of the participants. Therapeutic recommendations are made on the basis of this analysis with the recognition that the older clinical trial participants may not be representative of patients seen in daily practice. Patient selection and geriatric evaluation are critical for appropriate drug selection, dosing, and monitoring. With care, these therapies are a major step forward in the safe and effective treatment of older patients with cancer.

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