Avelumab: A Review in Metastatic Merkel Cell Carcinoma
In conclusion, currently available data suggest that avelumab present s a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis. (Source: Targeted Oncology)
Source: Targeted Oncology - May 24, 2018 Category: Cancer & Oncology Source Type: research

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer
AbstractAtezolizumab (TECENTRIQ ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patien ts with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials. In these studies, atezolizumab significantly prolonged overall survival (OS) relative to d...
Source: Targeted Oncology - May 21, 2018 Category: Cancer & Oncology Source Type: research

Prognostic Impact of the Components of Progressive Disease on Survival After First-Line Tyrosine Kinase Inhibitor Therapy for Metastatic Renal Cell Carcinoma
ConclusionsIn this retrospective single-center study, patients with TLG had poor survival after first-line TKI therapy for mRCC. Thus, individual components of PD influence patient prognosis. (Source: Targeted Oncology)
Source: Targeted Oncology - May 21, 2018 Category: Cancer & Oncology Source Type: research

Discovery of a Potent and Mutant-Selective EGFR Inhibitor that Overcomes T790M-Mediated Resistance in Lung Cancer
ConclusionsThese results identify OBX1-012 as a highly effective, mutant-selective EGFR-TKI for the treatment of T790M-mediated resistance in NSCLC. (Source: Targeted Oncology)
Source: Targeted Oncology - May 12, 2018 Category: Cancer & Oncology Source Type: research

Medical Treatment Options for Patients with Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer Suffering from Brain Metastases and/or Leptomeningeal Disease
AbstractBrain metastases and/or leptomeningeal disease (LMD) with associated central nervous system (CNS) metastases are known complications of advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). It is important, therefore, to assess the activity of EGFR tyrosine kinase inhibitors (TKIs) versus such CNS complications. This review explores the literature reporting the intracranial activity of EGFR TKIs, and finds that there is evidence for varying efficacy of the approved agents, erlotinib, gefitinib, afatinib, and osimertinib in patients with CNS metastases. Other EGFR TKI...
Source: Targeted Oncology - April 27, 2018 Category: Cancer & Oncology Source Type: research

The Role of Autophagy in the Resistance to BRAF Inhibition in BRAF -Mutated Melanoma
AbstractMalignant melanoma is the most aggressive and notorious skin cancer, and metastatic disease is associated with very poor long-term survival outcomes. Although metastatic melanoma patients with oncogenic mutations in theBRAF gene initially respond well to the treatment with specific BRAF inhibitors, most of them will eventually develop resistance to this targeted therapy. As a highly conserved catabolic process, autophagy is responsible for the maintenance of cellular homeostasis and cell survival, and is involved in multiple diseases, including cancer. Recent study results have indicated that autophagy might play a...
Source: Targeted Oncology - April 17, 2018 Category: Cancer & Oncology Source Type: research

The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review
AbstractMesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors....
Source: Targeted Oncology - April 14, 2018 Category: Cancer & Oncology Source Type: research

The Impact of Dose and Simultaneous Use of Acid-Reducing Agents on the Effectiveness of Vemurafenib in Metastatic BRAF V600 Mutated Melanoma: a Retrospective Cohort Study
ConclusionsThere was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating   full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation. (Source: Targeted Oncology)
Source: Targeted Oncology - April 11, 2018 Category: Cancer & Oncology Source Type: research

Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma
ConclusionsActivated STAT3 in tumor tissues shows a significant association with poor prognosis in patients with RCC who received sunitinib as a first-line therapy, and positive p-STAT3 expression could be a potential biomarker for refractoriness to sunitinib therapy. (Source: Targeted Oncology)
Source: Targeted Oncology - April 9, 2018 Category: Cancer & Oncology Source Type: research

Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies
ConclusionsPatients with mUC who progressed on atezolizumab were unlikely to receive subsequent systemic treatments and the benefit of those treatments appeared limited in our cohort. The findings may impact timing and designs of clinical trials in mUC. (Source: Targeted Oncology)
Source: Targeted Oncology - April 6, 2018 Category: Cancer & Oncology Source Type: research

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study
AbstractBackgroundRamucirumab —alone or combined with paclitaxel—represents one of the main options for patients failing first-line treatment for advanced gastric cancer.ObjectiveThe RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the “real-life setting”.Patients and MethodsPatients from 25 Italian hospitals started therapy consisting of ramucirumab 8  mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m2 i.v. d1,8,15q28. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall...
Source: Targeted Oncology - March 27, 2018 Category: Cancer & Oncology Source Type: research

Prognostic and Predictive Factors for Renal Cell Carcinoma
This article provides an overview of both clinical and molecular factors associated with predictive or prognostic value in mRCC and emphasizes that both should be considered in parallel to provide the most appropriate, individualized treatment and achieve the best outcomes in clinical practice. (Source: Targeted Oncology)
Source: Targeted Oncology - March 22, 2018 Category: Cancer & Oncology Source Type: research

Antibody –Drug Conjugates for the Treatment of Hematological Malignancies: A Comprehensive Review
AbstractAntibody –drug conjugates (ADCs) are an emerging class of therapeutic agents that bring new opportunities for the treatment of hematological malignancies by meeting unmet medical needs. These drugs consist of a cytotoxic agent connected by a linker to a human, humanized, or chimeric antibody targeting a su rface antigen specifically expressed by tumor cells. These ADCs are being developed to specifically deliver the cytotoxic agent into tumor cells. The cytotoxic payload is released from the ADC after internalization and cleavage of the linker, ultimately triggering the death of the cancer cell. Secon d- and ...
Source: Targeted Oncology - March 20, 2018 Category: Cancer & Oncology Source Type: research

Targeting BCL-2 in Hematologic Malignancies
AbstractResistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (C...
Source: Targeted Oncology - March 8, 2018 Category: Cancer & Oncology Source Type: research

Cabozantinib Versus Standard-of-Care Comparators in the Treatment of Advanced/Metastatic Renal Cell Carcinoma in Treatment-na ïve Patients: a Systematic Review and Network Meta-Analysis
ConclusionsThe results suggest that cabozantinib significantly increases PFS in intermediate-, and poor-risk subgroups when compared to standard-of-care comparators. Although overall populations included favorable risk patients in some studies, the results seen were consistent with the subgroup analyses. (Source: Targeted Oncology)
Source: Targeted Oncology - February 28, 2018 Category: Cancer & Oncology Source Type: research

The Abscopal Effect in the Era of Cancer Immunotherapy: a Spontaneous Synergism Boosting Anti-tumor Immunity?
AbstractRadiotherapy is one of the main treatment strategies used in cancer. Aside from the local control of the disease, which is mediated by a direct cytotoxic effect on tumor cells, radiotherapy has also been shown to exert immune-mediated local and systemic effects. Radiotherapy can elicit anti-tumor responses in distant sites from the radiation field; this phenomenon is known as the abscopal effect and has been described in patients previously treated with immune checkpoint blockade (ICB). Considering that the efficacy of immunotherapy has been demonstrated only in a subset of patients —who often benefit with la...
Source: Targeted Oncology - February 22, 2018 Category: Cancer & Oncology Source Type: research

Combining Ibrutinib with Chk1 Inhibitors Synergistically Targets Mantle Cell Lymphoma Cell Lines
ConclusionsThe pharmacological approach of simultaneously targeting cell cycle checkpoints (by Chk1 inhibitors) and pro-survival pathways (by ibrutinib) might offer a promising new therapeutic strategy for MCL patients. (Source: Targeted Oncology)
Source: Targeted Oncology - February 13, 2018 Category: Cancer & Oncology Source Type: research

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment
AbstractImmune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function th...
Source: Targeted Oncology - February 13, 2018 Category: Cancer & Oncology Source Type: research

Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations
AbstractAlpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pr e-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially w...
Source: Targeted Oncology - February 8, 2018 Category: Cancer & Oncology Source Type: research

Tumor Hypoxia As an Enhancer of Inflammation-Mediated Metastasis: Emerging Therapeutic Strategies
AbstractMetastasis is the leading cause of cancer-related deaths. Recent research has implicated tumor inflammation as a promoter of metastasis. Myeloid, lymphoid, and mesenchymal cells in the tumor microenvironment promote inflammatory signaling amongst each other and together with cancer cells to modulate sustained inflammation, which may enhance cancer invasiveness. Tumor hypoxia, a state of reduced available oxygen present in the majority of solid tumors, acts as a prognostic factor for a worse outcome and is known to have a role in tumor inflammation through the regulation of inflammatory mediator signals in both canc...
Source: Targeted Oncology - February 8, 2018 Category: Cancer & Oncology Source Type: research

Treatment of EGFR T790M-Positive Non-Small Cell Lung Cancer
AbstractThe treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic mutations of the epidermal growth factor receptor (EGFR). Despite remarkable initial responses, patients eventually develop progressive disease, with the most common cause of resistance to first-lineEGFR TKIs being the acquired T790M mutation. Various third-generationEGFR TKIs have been developed to specifically target this acquired mutation, of which osimertinib is currently the only approved agent. In addition, the eagerly anticipated data from the FLAURA study recently f...
Source: Targeted Oncology - February 8, 2018 Category: Cancer & Oncology Source Type: research

Induction chemotherapy with the EXTREME regimen in frail patients with locally advanced head and neck squamous cell carcinoma
ConclusionThis is the first study to report the use of the EXTREME regimen as induction chemotherapy, and although this IC was used in a very frail population, the majority completed the sequence with significant clinical benefit. (Source: Targeted Oncology)
Source: Targeted Oncology - February 5, 2018 Category: Cancer & Oncology Source Type: research

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients
ConclusionsNeoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature.Registration: The study is registered atClinicalTrials.gov (NCT00733889). (Source: Targeted Oncology)
Source: Targeted Oncology - February 1, 2018 Category: Cancer & Oncology Source Type: research

Extracellular Vesicles As miRNA Nano-Shuttles: Dual Role in Tumor Progression
AbstractTumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer, interacting with target cells of the tumor microenvironment, such as fibroblasts, immune and endothelial cells. EVs can modulate tumor progression, angiogenic switch, metastasis, and immune escape. These vesicles are nano-shuttles containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs contained in extracellular vesicles (EV-miRNAs) are disseminated in the extracellular space and are able to influence the  expression of target genes with either tumor suppressor or oncogenic functions, depending on both ...
Source: Targeted Oncology - January 26, 2018 Category: Cancer & Oncology Source Type: research

Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience
ConclusionsOur findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer. (Source: Targeted Oncology)
Source: Targeted Oncology - January 20, 2018 Category: Cancer & Oncology Source Type: research

Modulating Tumor Immunology by Inhibiting Indoleamine 2,3-Dioxygenase (IDO): Recent Developments and First Clinical Experiences
AbstractIndoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acidL-tryptophan toN-formyl-L-kynurenine. Through direct and indirect means, IDO exerts both tolerogenic and pro-inflammatory effects and has a profound immunoregulatory role in the tumor microenvironment. Although the role of IDO in mediating peripheral acquired immunologic tolerance has been known for some time, its role in tumorigenesis and the subversion of anti-tumor immunity have only r...
Source: Targeted Oncology - January 4, 2018 Category: Cancer & Oncology Source Type: research

Correction to: A Phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients
AbstractErrors were subsequently identified in the article and the following corrections should be noted (Source: Targeted Oncology)
Source: Targeted Oncology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Retreatment with Vismodegib after Progression in Advanced Basal Cell Carcinoma: First-Time Report of a Single-Institution Experience
The objective of our report is to determine whether vismodegib is still active when used in BCC patients who progressed during a first vismodegib course (FVC). We conducted a retrospective study on six advanced BCC patients enrolled in a clinical trial (STEVIE, NCT01367665) who discontinued vismodegib due to PD and were then retreated with the same drug. All patients underwent intercurrent therapies between the FVC and the second vismodegib course (SVC). Disease control (complete response, CR; partial response, PR; and stable disease) was achieved in 100% and 80% of cases in FVC and SVC, respectively. The overall response ...
Source: Targeted Oncology - December 12, 2017 Category: Cancer & Oncology Source Type: research

The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma
AbstractB-cell maturation antigen (BCMA) was originally identified as a cell membrane receptor, expressed exclusively on late stage B-cells and plasma cells (PCs). Investigations of BCMA as a target for therapeutic intervention in multiple myeloma (MM) were initiated in 2007, using cSG1 as a naked antibody (Ab) as well as an Ab –drug conjugate (ADC) targeting BCMA, ultimately leading to ongoing clinical studies for previously treated MM patients. Since then, multiple companies have developed anti-BCMA-directed ADCs. Additionally, there are now three bispecific antibodies in development, which bind to both BCMA and CD...
Source: Targeted Oncology - December 11, 2017 Category: Cancer & Oncology Source Type: research

Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review
AbstractInhibition of DNA methyltransferases (DNMTs) has emerged as a novel treatment strategy in solid tumors. Aberrant hypermethylation in promoters of critical tumor suppressor genes is the basis for the idea that treatment with hypomethylating agents may lead to the restoration of a “normal” epigenome and produce clinically meaningful therapeutic outcomes. The aim of this review article is to summarize the current state of knowledge of DNMT inhibitors in the treatment of genitourinary malignancies. The efficacy of these agents in genitourinary malignancies was reported in a number of studies and suggests a ...
Source: Targeted Oncology - December 11, 2017 Category: Cancer & Oncology Source Type: research

Motivation for Launching a Cancer Metastasis Inhibition (CMI) Program
AbstractMetastatic cancers impose significant burdens on patients, affecting quality of life, morbidity, and mortality. Even during remission, microscopic metastases can lurk, but few therapies directly target tumor cell metastasis. Agents that interfere with this process would represent a new paradigm in cancer management, changing the ‘waiting game’ into a time of active prevention. These therapies could take multiple forms based on the pathways involved in the metastatic process. For example, a phenome-wide association study showed that a single nucleotide polymorphism in the geneTBXA2R is associated with in...
Source: Targeted Oncology - December 7, 2017 Category: Cancer & Oncology Source Type: research

Early Metabolic Change after Induction Chemotherapy Predicts Histologic Response and Prognosis in Patients with Esophageal Cancer: Secondary Analysis of a Randomized Trial
ConclusionEarly PET response after IC is prognostic, but subsequent PET changes (for example, after chemoradiation) are not prognostic. Early PET response might have the potential of predicting pCR. (Source: Targeted Oncology)
Source: Targeted Oncology - December 7, 2017 Category: Cancer & Oncology Source Type: research

Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions
AbstractCell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are involved in the regulation of the cell cycle, are frequently overexpressed or mutated in cancer. Hence, CDK-inhibiting drugs have been developed and evaluated as cancer therapeutics. Clinical trials have shown CDK4/6 inhibitors (CDK4/6i) to be relatively safe and effective, and these are now standard of care treatment for advanced hormone receptor positive breast cancer. Some CDK4/6i drugs are also able to cross the blood brain barrier and may, therefore, off...
Source: Targeted Oncology - December 7, 2017 Category: Cancer & Oncology Source Type: research

Phase IB Trial of the Anti-Cancer Stem Cell DLL4-Binding Agent Demcizumab with Pemetrexed and Carboplatin as First-Line Treatment of Metastatic Non-Squamous NSCLC
ConclusionsThis study has identified a truncated dosing regimen and recommended phase II dose of demcizumab (5  mg/kg q3-weekly ×4) for subsequent clinical evaluation in combination with standard carboplatin and pemetrexed chemotherapy. NCT01189968. (Source: Targeted Oncology)
Source: Targeted Oncology - November 29, 2017 Category: Cancer & Oncology Source Type: research

Phase II Study of Gemcitabine Plus Sirolimus in Previously Treated Patients with Advanced Soft-Tissue Sarcoma: a Spanish Group for Research on Sarcomas (GEIS) Study
ConclusionsThe combination of gemcitabine and sirolimus is an active treatment in STS. Further investigation is warranted.ClinicalTrials.gov identifier: NCT01684449. (Source: Targeted Oncology)
Source: Targeted Oncology - November 24, 2017 Category: Cancer & Oncology Source Type: research

The Treatment Landscape and New Opportunities of Molecular Targeted Therapies in Gastroenteropancreatic Neuroendocrine Tumors
AbstractNeuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms that originate from neuroendocrine stem cells and express both neural and endocrine markers. They are found in almost every organ, and while NENs are mostly associated with slow growth, complications due to the uncontrolled secretion of active peptides, and metastatic disease, may significantly impair the quality of life and can ultimately lead to the  death of affected individuals. Expanding knowledge of the genetic, epigenetic, and proteomic landscapes of NENs has led to a better understanding of their molecular pathology and consequently...
Source: Targeted Oncology - November 15, 2017 Category: Cancer & Oncology Source Type: research

Cetuximab/TPF/radiotherapy in oesophageal cancer
ConclusionsNeoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature.Registration: The study is registered atClinicalTrials.gov (NCT00733889). (Source: Targeted Oncology)
Source: Targeted Oncology - November 11, 2017 Category: Cancer & Oncology Source Type: research

Antibody –Drug Conjugates for the Treatment of Solid Tumors: Clinical Experience and Latest Developments
AbstractAntibody –drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecula r linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-pos...
Source: Targeted Oncology - November 8, 2017 Category: Cancer & Oncology Source Type: research

Acknowledgement to Referees
(Source: Targeted Oncology)
Source: Targeted Oncology - November 8, 2017 Category: Cancer & Oncology Source Type: research

Trastuzumab in Combination with FOLFIRI in Patients with Advanced HER2-Positive Gastro-Esophageal Adenocarcinoma: A Retrospective Multicenter AGEO Study
ConclusionsThis is the first western population-based study of FOLFIRI plus trastuzumab reporting a satisfactory safety profile and a potential efficacy in advanced HER2-positive gastric cancer. (Source: Targeted Oncology)
Source: Targeted Oncology - October 31, 2017 Category: Cancer & Oncology Source Type: research

Comment on: “Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)”
(Source: Targeted Oncology)
Source: Targeted Oncology - October 28, 2017 Category: Cancer & Oncology Source Type: research

Author ’s Reply to Arnaud Uguen: “Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)”
(Source: Targeted Oncology)
Source: Targeted Oncology - October 28, 2017 Category: Cancer & Oncology Source Type: research

A Multi-Arm Phase I Study of the PI3K/mTOR Inhibitors PF-04691502 and Gedatolisib (PF-05212384) plus Irinotecan or the MEK Inhibitor PD-0325901 in Advanced Cancer
ConclusionsFurther evaluations of gedatolisib are warranted in patients with advanced solid malignancies. (Source: Targeted Oncology)
Source: Targeted Oncology - October 24, 2017 Category: Cancer & Oncology Source Type: research

Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with the Second-Generation ALK Inhibitor Ceritinib
ConclusionThis study shows that monotherapy with an ALK inhibitor, such as ceritinib, in RMS, has no effect on ALK signaling. However, the synergistic effects of ceritinib and dasatinib are promising, most probably due to targeting of IGF1R and Src. (Source: Targeted Oncology)
Source: Targeted Oncology - October 24, 2017 Category: Cancer & Oncology Source Type: research

CEA Response and Depth of Response (DpR) to Predict Clinical Outcomes of First-Line Cetuximab Treatment for Metastatic Colorectal Cancer
AbstractBackgroundThe decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab.ObjectiveWe investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment.Patients and MethodsAssociations among the CEA decrease, depth of response (DpR), and clinical outcomes were evaluated in 113 patients wit...
Source: Targeted Oncology - October 24, 2017 Category: Cancer & Oncology Source Type: research

Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between Elderly and Younger Patients: a Study Using the International Pharmacovigilance Database
This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life.Patients and MethodsAn extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and
Source: Targeted Oncology - October 11, 2017 Category: Cancer & Oncology Source Type: research

The Current Landscape of Anaplastic Lymphoma Kinase ( ALK ) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions
AbstractTumorigenic rearrangements in anaplastic lymphoma kinase (ALK) account for 3 –7% of all non-small cell lung cancers (NSCLC). Treatment with targeted tyrosine kinase inhibitors (TKIs) has shown impressive clinical responses. Crizotinib was the first agent approved for front-line therapy ofALK-rearranged NSCLC after it demonstrated superiority to chemotherapy in response rate, duration of response, and progression-free survival. However, eventually all patients progress on crizotinib therapy, with the central nervous system (CNS) being the most common site, which served as the impetus for the development of mor...
Source: Targeted Oncology - August 31, 2017 Category: Cancer & Oncology Source Type: research

Insulin-Like Growth Factor (IGF) Pathway Targeting in Cancer: Role of the IGF Axis and Opportunities for Future Combination Studies
AbstractDespite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair. Consequently, comb...
Source: Targeted Oncology - August 16, 2017 Category: Cancer & Oncology Source Type: research

Dose and Schedule Selection of the Oral Proteasome Inhibitor Ixazomib in Relapsed/Refractory Multiple Myeloma: Clinical and Model-Based Analyses
ConclusionsThese analyses support a favorable benefit –risk profile for weekly ixazomib 4.0 mg on days 1, 8, and 15 of 28-day cycles, which was selected for the phase III TOURMALINE registration program.Trial Registration NumbersClinicalTrials.gov NCT00932698, NCT00963820, NCT01217957, NCT01564537 (Source: Targeted Oncology)
Source: Targeted Oncology - August 12, 2017 Category: Cancer & Oncology Source Type: research

Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars
This article reviews the current role of bevacizumab in the management of mCRC, the possible barriers associated with diminished access to bevacizumab, and the potential bevacizumab biosimilars in development. How biosimilars may impact the treatment of mCRC is also discussed. (Source: Targeted Oncology)
Source: Targeted Oncology - August 11, 2017 Category: Cancer & Oncology Source Type: research