Cancer Targeted Therapies
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Merck's PD-1 star Keytruda shines at ASH, but lags behind Bristol-Myers' rival

Merck's PD-1 star Keytruda shines at ASH, but lags behind Bristol-Myers' rival | Cancer Targeted Therapies | Scoop.it
Merck's new PD-1 cancer drug Keytruda (pembrolizumab) has posted another round of positive early-stage results that help demonstrate its potential in an important cancer R&D arena: hematology.

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Krishan Maggon 's curator insight, December 7, 2014 3:02 AM

The results favor Nivolumab with 87% ORR in difficult to treat relapsed or refreactory Hodgkin Lymphoma. Higher 17% CR and 70% PR in the trial.

 

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66% ORR in refractory Hodgkin Lymphoma.

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Identificado un tratamiento que podría resultar eficaz frente al cáncer de pulmón más prevalente

Identificado un tratamiento que podría resultar eficaz frente al cáncer de pulmón más prevalente | Cancer Targeted Therapies | Scoop.it
La combinación de dos fármacos experimentales logra que el cáncer de pulmón no microcítico resistente sea susceptible a la radioterapia
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Un estudio llevado a cabo con modelos animales –ratones– por Investigadores de la Universidad Thomas Jefferson en Filadelfia (EE.UU.), la solución podría encontrarse en la combinación de dos fármacos anticancerígenos experimentales y radioterapia.

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Personalized Cellular Therapy for Brain Cancer

Personalized Cellular Therapy for Brain Cancer | Cancer Targeted Therapies | Scoop.it
EGFRvIII
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Interesting article for glioblastoma -EGFRvIII is part of our package PLUS with OncoDEEP DX & Clinical -we are uptodate !!!!


A study published in Science Translational Medicine showed that immune cells engineered to seek out and attack a type of deadly brain cancer can be both safe and effective at controlling tumor growth in mice reated with these modified cells. A team from the Perelman School of Medicine at the University of Pennsylvania and the Novartis Institutes for BioMedical Research has paved the way for a newly opened clinical trial for glioblastoma patients at Penn.


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Traitement des cancers : de nouvelles avancées en immunothérapie | Fondation ARC pour la recherche sur le cancer

Traitement des cancers : de nouvelles avancées en immunothérapie | Fondation ARC pour la recherche sur le cancer | Cancer Targeted Therapies | Scoop.it
Etude sur l'utilisation d'anticorps dirigés contre la protéine PD-L1, dans des cas de cancers métastatiques.
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Pfizer Announces Palbociclib PALOMA-1 Data Published in The Lancet Oncology

Pfizer Announces Palbociclib PALOMA-1 Data Published in The Lancet Oncology | Cancer Targeted Therapies | Scoop.it
From BioPortfolio: Pfizer Inc. (NYSE:PFE) today announced the publication of the detailed results from PALOMA-1, a randomized Phase 2 study of palbociclib in combination with letr...
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Pfizer Inc. (NYSE:PFE) today announced the publication of the detailed results from PALOMA-1, a randomized Phase 2 study of palbociclib in combination with letrozole versus letrozole alone, in The Lancet Oncology. As previously disclosed, PALOMA-1 achieved its primary endpoint with the combination of palbociclib and letrozole significantly prolonging progression-free survival (PFS) compared with letrozole alone in post-menopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer.

A New Drug Application (NDA) for palbociclib was accepted for filing and granted Priority Review by the United States Food and Drug Administration (FDA). This NDA is based on the final results of PALOMA-1. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is April 13, 2015. IBRANCETM is the proposed trade name for palbociclib.

“The publication of the PALOMA-1 data in The Lancet Oncology marks another important milestone in the path to bring IBRANCETM, the proposed trade name for palbociclib, to women with ER+, HER2- metastatic breast cancer, who haven’t seen a first-line treatment advance in more than 10 years,” said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs and Chief Medical Officer for Pfizer Oncology.

Results from PALOMA-1 were presented by lead author Dr. Richard Finn at the American Association for Cancer Research (AACR) Annual Meeting 2014. PALOMA-1 was conducted in collaboration with the Jonsson Comprehensive Cancer Center’s Revlon/UCLA Women’s Cancer Research Program, led by Dr. Dennis Slamon.

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Merck's PD-1 star Keytruda shines at ASH, but lags behind Bristol-Myers' rival

Merck's PD-1 star Keytruda shines at ASH, but lags behind Bristol-Myers' rival | Cancer Targeted Therapies | Scoop.it
Merck's new PD-1 cancer drug Keytruda (pembrolizumab) has posted another round of positive early-stage results that help demonstrate its potential in an important cancer R&D arena: hematology.

Via Krishan Maggon
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Krishan Maggon 's curator insight, December 7, 2014 3:02 AM

The results favor Nivolumab with 87% ORR in difficult to treat relapsed or refreactory Hodgkin Lymphoma. Higher 17% CR and 70% PR in the trial.

 

vs 

 

66% ORR in refractory Hodgkin Lymphoma.

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MPDL3280A (anti-PD-L1, Roche) treatment leads to clinical activity in metastatic bladder cancer

Roche anti PDL1 antibody showed activity in Phase I trial in advanced metastatic bladder cancer. A total of 68 patients enrolled in trial, 2 had complete remission or response and more that half of the treated patients showed benefits of PDL1 therapy, tumor regression  PR/SD and longer PFS.

 

 


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Krishan Maggon 's curator insight, November 28, 2014 7:05 AM
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancerThomas Powles,Joseph Paul Eder,Gregg D. Fine,Fadi S. Braiteh,Yohann Loriot,Cristina Cruz,Joaquim Bellmunt,Howard A. Burris,Daniel P. Petrylak,Siew-leng Teng,Xiaodong Shen,Zachary Boyd,Priti S. Hegde,Daniel S. Chen& Nicholas J. VogelzangAffiliationsContributionsCorresponding authorNature 515, 558–562 (27 November 2014) doi:10.1038/nature13904Received 23 May 2014 Accepted 30 September 2014 Published online 26 November 2014
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Celldex Immunotherapy Prolongs Survival for Recurrent Brain Tumor Patients - TheStreet.com

Celldex Immunotherapy Prolongs Survival for Recurrent Brain Tumor Patients - TheStreet.com | Cancer Targeted Therapies | Scoop.it
Positive data presented Friday, particularly the statistically significant survival benefit favoring patients treated with rindopepimut, has Celldex planning -- cautiously -- for a conversation with the FDA about accelerated approval.
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HAMPTON, NJ (TheStreet) -- Treatment with an experimental, targeted immunotherapy developed by Celldex Therapeutics (CLDX) added to Roche's (RHHBY) Avastin is delaying tumor growth and extending survival in patients with a certain type of recurrent brain tumor, according to interim results from a mid-stage study presented Friday at a medical meeting.

The Celldex cancer immunotherapy used in the study is known as rindopepimut. The company designed the phase II study in recurrent brain tumors to be "exploratory" -- meaning it didn't expect the rindopepimut results to be strong enough for regulatory approval. But the positive data presented Friday, particularly the statistically significant survival benefit favoring patients treated with rindopepimut, has Celldex planning -- cautiously -- for a conversation with the FDA about accelerated approval.

"We're very happy with the interim results, but we're trying to be conservative, so we'll wait for the final data in three to six months. If the results are consistent, we'll meet with the FDA," said Celldex CEO Anthony Marucci.


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Bristol-Myers immunotherapy shows promise to replace chemo for melanoma

(Reuters) - Chemotherapy as a treatment for advanced melanoma could soon become obsolete, researchers said on Sunday, after patients taking an experimental immuno-oncology drug from Bristol-Myers Squibb Co had a much higher survival rate and had other favorable results.

The impressive results, compared with chemo, were seen in a late-stage study of the Bristol-Myers drug Opdivo, which helps take the brakes off the immune system by blocking the protein PD-1.

The 418-patient-study involved previously untreated patients with advanced melanoma, the most deadly form of skin cancer. Among those taking Opdivo, 73 percent were alive one year later, compared with 42 percent of those receiving standard chemo treatment dacarbazine.

Moreover, 40 percent of those taking Opdivo had tumor shrinkage, versus 14 percent for the chemo group. The treatment was associated with mild side effects, including fatigue and nausea.

"The results were incredibly good and show there will no longer be a role for chemotherapy in advanced melanoma," said Dr. Georgina Long, an associate professor at the Melanoma Institute Australia who helped lead the study.

Findings were presented at a medical meeting in Zurich.

Long, reached by phone there, said the findings bode well not only for Opdivo, but for an emerging crop of other PD-1 inhibitors being developed by other companies. They include products being tested by Merck & Co, Roche Holding AG and AstraZeneca Plc.

Merck's Keytruda in September received the first U.S. approval of a drug from the class, to treat advanced melanoma.

Opdivo had also shown strong results in a different Phase III trial that involved advanced melanoma patients who had previously been treated with Yervoy, another immuno-oncology drug from Bristol-Myers. Those results, released in September, showed tumors shrank in 32 percent of patients given Opdivo, compared with 11 percent of those receiving chemo.

Bristol-Myers is testing Opdivo for many other cancers, with early glimpses of success.

Treatment of a common form of advanced lung cancer with the drug led to a one-year survival rate of 41 percent in a midstage clinical trial, according to data presented two weeks ago.

The historical one-year survival rate for such patients, who previously failed on other drugs, is between 5.5 percent and 18 percent.

(Reporting by Ransdell Pierson; Editing by Leslie Adler)
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(Reuters) - Chemotherapy as a treatment for advanced melanoma could soon become obsolete, researchers said on Sunday, after patients taking an experimental immuno-oncology drug from Bristol-Myers Squibb Co had a much higher survival rate and had other favorable results.

The impressive results, compared with chemo, were seen in a late-stage study of the Bristol-Myers drug Opdivo, which helps take the brakes off the immune system by blocking the protein PD-1.

The 418-patient-study involved previously untreated patients with advanced melanoma, the most deadly form of skin cancer. Among those taking Opdivo, 73 percent were alive one year later, compared with 42 percent of those receiving standard chemo treatment dacarbazine.

Moreover, 40 percent of those taking Opdivo had tumor shrinkage, versus 14 percent for the chemo group. The treatment was associated with mild side effects, including fatigue and nausea.

"The results were incredibly good and show there will no longer be a role for chemotherapy in advanced melanoma," said Dr. Georgina Long, an associate professor at the Melanoma Institute Australia who helped lead the study.

Findings were presented at a medical meeting in Zurich.

Long, reached by phone there, said the findings bode well not only for Opdivo, but for an emerging crop of other PD-1 inhibitors being developed by other companies. They include products being tested by Merck & Co, Roche Holding AG and AstraZeneca Plc.

Merck's Keytruda in September received the first U.S. approval of a drug from the class, to treat advanced melanoma.

Opdivo had also shown strong results in a different Phase III trial that involved advanced melanoma patients who had previously been treated with Yervoy, another immuno-oncology drug from Bristol-Myers. Those results, released in September, showed tumors shrank in 32 percent of patients given Opdivo, compared with 11 percent of those receiving chemo.

Bristol-Myers is testing Opdivo for many other cancers, with early glimpses of success.

Treatment of a common form of advanced lung cancer with the drug led to a one-year survival rate of 41 percent in a midstage clinical trial, according to data presented two weeks ago.

The historical one-year survival rate for such patients, who previously failed on other drugs, is between 5.5 percent and 18 percent.



(Reporting by Ransdell Pierson; Editing by Leslie Adler)


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A step towards personalised cancer treatments

A step towards personalised cancer treatments | Cancer Targeted Therapies | Scoop.it
Sequencing the genomes of tumor cells has revealed thousands of genetic mutations linked with cancer. However, sifting through this deluge of information to figure out which of these mutations actually drive cancer growth has proven to be a tedious, time-consuming process. MIT researchers have now developed a new way to model the effects of these […]
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FOLFOXIRI + Bevacizumab Ups Outcome in Metastatic Colorectal Cancer

FOLFOXIRI + Bevacizumab Ups Outcome in Metastatic Colorectal Cancer | Cancer Targeted Therapies | Scoop.it
-- For patients with untreated metastatic colorectal cancer, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab improves outcome versus fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab, according to a study published in the Oct. 23 issue of the New England Journal of Medicine.
Fotios Loupakis, MD, PhD, from the Università di Pisa in Italy, and colleagues randomized 508 patients with untreated metastatic colorectal cancer to receive FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles were administered, and fluorouracil plus bevacizumab was continued until disease progression.

The researchers found that the median progression-free survival was 12.1 and 9.7 months in the experimental and control groups, respectively (hazard ratio for progression, 0.75; P = 0.003). In the experimental and control groups, the objective response rate was 65 and 53%, respectively (P = 0.006). The experimental group had a trend toward longer overall survival (31.0 versus 25.8 months; hazard ratio for death, 0.79; 95% confidence interval, 0.63 to 1.00; P = 0.054). The experimental group had significantly higher incidences of grade 3 and 4 neurotoxicity, stomatitis, diarrhea, and neutropenia.

"FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events," the authors write.
OncoDNA's insight:

-- For patients with untreated metastatic colorectal cancer, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab improves outcome versus fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab, according to a study published in the Oct. 23 issue of the New England Journal of Medicine.

Fotios Loupakis, MD, PhD, from the Università di Pisa in Italy, and colleagues randomized 508 patients with untreated metastatic colorectal cancer to receive FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles were administered, and fluorouracil plus bevacizumab was continued until disease progression.

The researchers found that the median progression-free survival was 12.1 and 9.7 months in the experimental and control groups, respectively (hazard ratio for progression, 0.75; P = 0.003). In the experimental and control groups, the objective response rate was 65 and 53%, respectively (P = 0.006). The experimental group had a trend toward longer overall survival (31.0 versus 25.8 months; hazard ratio for death, 0.79; 95% confidence interval, 0.63 to 1.00; P = 0.054). The experimental group had significantly higher incidences of grade 3 and 4 neurotoxicity, stomatitis, diarrhea, and neutropenia.

"FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events," the authors write.

- See more at: http://www.hcplive.com/articles/FOLFOXIRI-and43-Bevacizumab-Ups-Outcome-in-Metastatic-Colorectal-Cancer?sthash.gjqJvlVC.mjjo&__scoop_post=80f0d820-5bea-11e4-a07c-001018304b75&__scoop_topic=3545156#__scoop_post=80f0d820-5bea-11e4-a07c-001018304b75&__scoop_topic=3545156


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Implementing personalized cancer genomics in clinical trials : Nature Reviews Drug Discovery : Nature Publishing Group

Implementing personalized cancer genomics in clinical trials : Nature Reviews Drug Discovery : Nature Publishing Group | Cancer Targeted Therapies | Scoop.it
Implementing personalized cancer genomics in clinical trials (2013) Great review, open access http://t.co/T27030Tj27
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Landscape Analysis Reveals How Little Is Known, Or Said, About Metastatic ... - Forbes

Landscape Analysis Reveals How Little Is Known, Or Said, About Metastatic ... - Forbes | Cancer Targeted Therapies | Scoop.it
Many patients living with metastatic breast cancer need more help than they’re receiving, and many are reluctant to ask.
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Today the Metastatic Breast Cancer Alliance put forth a landscape analysis on the needs of patients with metastatic breast cancer (MBC). This report follows and refers to a recent, Pfizer-backed survey of 2,090 men and women which revealed major deficiencies in common knowledge about the condition.


Among U.S. adults surveyed in April 2014, 72 percent (mistakenly) believe that advanced breast cancer is curable if detected early. Half of the respondents suggested that people living with metastatic disease have it because they didn’t take appropriate treatment or preventive measures. As summarized in the larger report, over 60 percent said they knew “little or nothing” about metastatic breast cancer.


“There are a lot of people who don’t know what metastatic breast cancer is,” saidDeAngelo Williams, a running back for the Carolina Panthers at a meeting of the Alliance held today in Manhattan. The football player spoke of his mother’s death last spring at age 53, while receiving hospice care, from metastatic breast cancer. The disease also took the lives of four of Williams’s aunts. “When breast cancer took my mom, it met its biggest enemy,” he told the group.


The Metastatic Breast Cancer Alliance, founded one year ago, represents a cooperative effort among over twenty cancer charities and industry. The Alliance has received support from Celgene, Eisai, Eli Lilly Genentech, Lilly, Novartis and Pfizer. In addition, the Avon Foundation for Women has provided major administrative support to the group, including personnel.


The Alliance used a mix of literature reviews and meta-analyses, along with interviews with scientists, patients, caregivers and “thought leaders,” to explore five areas relevant to advanced breast cancer: research including basic science and clinical trials; quality of life concerns; available information and support for people living with the condition and for their caretakers; epidemiology; and public awareness.


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Getting Personalized: Therapeutic Targeting of Brain Tumors Gets Smarter Through Genomics

Getting Personalized: Therapeutic Targeting of Brain Tumors Gets Smarter Through Genomics | Cancer Targeted Therapies | Scoop.it
Many patients with glioblastoma or meningioma at Cleveland Clinic are now offered genomic profiling of their tumors. Here’s why, along with a glimpse of where the practice is taking brain tumor therapy.
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Genomic profiling helps guide drug therapy for select tumors

Personalized medicine services have been part of the toolbox of the Neurological Institute’s Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center since 1999, when 1p chromosome deletion testing was first offered. After adding more and more such services in the ensuing years, the center decided in 2013 to begin offering patients with select brain tumors the option of having their tumor tissue undergo genomic profiling to test for thousands of genetic abnormalities that could potentially impact their treatment.

“As we’ve offered more personalized medicine over the years, we’ve reached the point where it clearly makes sense to perform personalized tumor testing for genetic abnormalities in some cases rather than offer just a few specific tests,” says Gene Barnett, MD, MBA, Director of the Burkhardt  Brain Tumor Center, which works closely with Cleveland Clinic’s Taussig Cancer Institute.

A road map to more rational drug selection

The Burkhardt Brain Tumor Center offers genomic profiling primarily for patients with new or recurrent glioblastoma, or atypical or malignant meningioma. It can provide a more rational basis on which to choose drug therapies, be they conventional or investigational, by offering data about particular characteristics that a patient’s tumor may have.


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Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents: Cancer Cell

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The Coming Wave of New Cancer-Fighting Drugs

The Coming Wave of New Cancer-Fighting Drugs | Cancer Targeted Therapies | Scoop.it
The hottest area in cancer drugs is going mainstream this year.
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Pancreatic Cancer

Pancreatic Cancer | Cancer Targeted Therapies | Scoop.it
Pancreatic cancer is the most lethal cancer, and new therapies are urgently needed to impact pancreatic cancer treatment and to extend and save pancreatic cancer patients’ lives.
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FDA Approves Ramucirumab for Treatment of Metastatic NSCLC | ESMO

It is a third indication the drug has received in 2014
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On 12 December, 2014 the USA Food and Drug Administration (FDA) expanded the approved use of ramucirumab (Cyramza) to treat patients with metastatic non-small-cell lung cancer (NSCLC). The drug is intended for patients whose tumour has progressed during or following treatment with platinum-based chemotherapy, and it is to be used in combination with docetaxel.

Ramucirumabis a fully human monoclonal antibody (IgG1) directed against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2, it works as a receptor antagonist blocking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority of the downstream effects of VEGF in angiogenesis.

“Today’s approval is the third indication that Cyramza has received in 2014,” said Dr Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The commitment to study Cyramza in a variety of malignancies provides important treatment options to patients.”

On 21 April, the FDA approved ramucirumab as a single agent to treat patients with advanced gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma. On 5 November, the FDA expanded ramucirumab’s use to treat patients with advanced gastric or GEJ adenocarcinoma in its combination with paclitaxel. 

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How Personalized Medicine is Changing: Lung Cancer

How Personalized Medicine is Changing: Lung Cancer | Cancer Targeted Therapies | Scoop.it
Stephanie Dunn Haney never felt a sense of urgency about the pain on the right side of her chest. The discomfort only occurred when she …
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Pembrolizumab Shows Promise in Advanced Gastric Cancer

Pembrolizumab Shows Promise in Advanced Gastric Cancer | Cancer Targeted Therapies | Scoop.it
Pembrolizumab Shows Promise in Advanced Gastric Cancer http://t.co/cxHtAAWq52
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MSD Announces Positive Study Investigating the Use of Pembrolizumab Compared to Chemotherapy in Patients with Ipilimumab-Refractory Advanced Melanoma | Merck Newsroom Home

MSD Announces Positive Study Investigating the Use of Pembrolizumab Compared to Chemotherapy in Patients with Ipilimumab-Refractory Advanced Melanoma | Merck Newsroom Home | Cancer Targeted Therapies | Scoop.it
ZURICH--(BUSINESS WIRE)--MSD, known as Merck in the United States and Canada, announced today that a pre-specified analysis of investigational data from a pivotal Phase 2 study (KEYNOTE-002) showed pembrolizumab, the company’s anti-PD-1 therapy,...

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Krishan Maggon 's curator insight, November 16, 2014 6:38 AM

Pembrolizumab Demonstrated Superiority to Chemotherapy for Primary Endpoint of Progression-Free Survival


Findings Presented for First Time at Society of Melanoma Research (SMR) 2014 International Congress

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Merck Receives FDA Breakthrough Therapy Designation for KEYTRUDA® (pembrolizumab) in Advanced Non-Small Cell Lung Cancer | Merck Newsroom Home

@Merck Receives @US_FDA Breakthrough Designation for #KEYTRUDA (#pembrolizumab) in Advanced #LungCancer http://t.co/o6UwtUPfUQ

 

Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy. This is the second Breakthrough Therapy Designation granted for KEYTRUDA.

 

The Breakthrough Therapy Designation in advanced NSCLC is supported by data from the ongoing Phase 1b KEYNOTE-001 study, and updated findings were recently presented at the European Society of Medical Oncology (ESMO) 2014 Congress. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. KEYTRUDA was previously granted breakthrough status for advanced melanoma.

 

KEYTRUDA is being studied across more than 30 types of cancers, as monotherapy and in combination. In advanced lung cancer, Merck is advancing a clinical program investigating the use of KEYTRUDA as monotherapy and in combination across lines of therapy and histology, including exploring different tumor characteristics such as PD-L1 expression as predictors of responsiveness. There are two ongoing Phase 2 and 3 studies in advanced lung cancer (KEYNOTE-010 and KEYNOTE-024) and an additional Phase 3 study is planned to begin in the fourth quarter of 2014 (KEYNOTE-042).

 


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Krishan Maggon 's curator insight, October 27, 2014 10:06 AM

Based on ESMO 2014 data.

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Concept to Clinic: CDK 4/6 Inhibition in ER-Positive Breast Cancer

Concept to Clinic: CDK 4/6 Inhibition in ER-Positive Breast Cancer | Cancer Targeted Therapies | Scoop.it
Recent data indicate a role for a pathway involved in controlling cell proliferation as a potential site for therapeutic intervention in breast cancer (BC). The concept of intervening in cell cycle control in cancer is not new, but has been borne out in preclinical studies, and is now offering real possibilities for treatment in women with BC who fail a commonly used endocrine therapy.
An Essential Regulatory Pathway

Unrestrained cell proliferation is a defining feature in cancer, and it is understood that, under normal conditions, this process is tightly regulated at many levels, one of which is the cell cycle.1,2 In a critical cell cycle ‘checkpoint’ mitogenic signals cause upregulation of cyclin D1, which binds to, and activates, cyclindependent kinases (CDKs) 4 and 6. CDKs 4 and 6, when activated, phosphorylate the retinoblastoma (Rb) protein, an event which causes its release from the E2F transcription factor.2,3 The release of E2F results in the transcriptional regulation of genes involved in the subsequent transition from the G1 phase of the cycle to the DNA synthesis (S) phase.2,3 Additional control is provided by inhibitors of CDK 4/6, such as p21 and p16.2

Mateusz Opyrchal, MD, PhD, assistant professor of oncology at the Roswell Park Cancer Institute, Buffalo, New York, noted the considerable effort under way to examine the role of CDKs in oncogenesis and progression of cancers.

“CDKs play an important role in regulating cell division, and they guide many processes before and during the cell division, making this a highly regulated process. In cancers, aberrations in CDK function, and specifically in the CDK 4/6 and Rb pathway, which regulates initiation of gene transcription, lead to increased cell proliferation and tumor growth, as well as resistance to treatments,” Opyrchal said. Early evidence for a role of the CDK 4/6 pathway in BC came from key findings, such as cyclin D1 overexpression and dysregulation of Rb function in BC.4,5
OncoDNA's insight:

Recent data indicate a role for a pathway involved in controlling cell proliferation as a potential site for therapeutic intervention in breast cancer (BC). The concept of intervening in cell cycle control in cancer is not new, but has been borne out in preclinical studies, and is now offering real possibilities for treatment in women with BC who fail a commonly used endocrine therapy.

An Essential Regulatory Pathway

Unrestrained cell proliferation is a defining feature in cancer, and it is understood that, under normal conditions, this process is tightly regulated at many levels, one of which is the cell cycle.1,2 In a critical cell cycle ‘checkpoint’ mitogenic signals cause upregulation of cyclin D1, which binds to, and activates, cyclindependent kinases (CDKs) 4 and 6. CDKs 4 and 6, when activated, phosphorylate the retinoblastoma (Rb) protein, an event which causes its release from the E2F transcription factor.2,3 The release of E2F results in the transcriptional regulation of genes involved in the subsequent transition from the G1 phase of the cycle to the DNA synthesis (S) phase.2,3 Additional control is provided by inhibitors of CDK 4/6, such as p21 and p16.2

Mateusz Opyrchal, MD, PhD, assistant professor of oncology at the Roswell Park Cancer Institute, Buffalo, New York, noted the considerable effort under way to examine the role of CDKs in oncogenesis and progression of cancers.

“CDKs play an important role in regulating cell division, and they guide many processes before and during the cell division, making this a highly regulated process. In cancers, aberrations in CDK function, and specifically in the CDK 4/6 and Rb pathway, which regulates initiation of gene transcription, lead to increased cell proliferation and tumor growth, as well as resistance to treatments,” Opyrchal said. Early evidence for a role of the CDK 4/6 pathway in BC came from key findings, such as cyclin D1 overexpression and dysregulation of Rb function in BC.4,5 - See more at: http://www.targetedonc.com/publications/targeted-therapy-news/2014/sept-2014/concept-to-clinic-cdk-46-inhibition-in-er-positive-breast-cancer?__scoop_post=c9f4cee0-5b46-11e4-dbc6-001018304b75&__scoop_topic=3545156#__scoop_post=c9f4cee0-5b46-11e4-dbc6-001018304b75&__scoop_topic=3545156


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Living with Stage 4: The breast cancer no one understands

Living with Stage 4: The breast cancer no one understands | Cancer Targeted Therapies | Scoop.it
A no-nonsense Texan of 60 years, Jody Schoger has a very no-nonsense way of educating people about her metastatic breast cancer.

“Someone will say, ‘When are you done with treatment?’ and I’ll tell them, ‘When I’m dead,’” said Schoger, a writer and cancer advocate who lives near Houston.  “So many people interpret survivorship as going across the board. That everybody survives cancer now. But everybody does not survive cancer.”

An estimated 155,000 plus women (and men) in the U.S. currently live with “mets,” Stage 4 breast cancer that’s traveled through the bloodstream to create tumors in the liver, lungs, brain, bones and/or other parts of the body. While treatable, metastatic breast cancer (MBC) is incurable. Between 20 and 30 percent of women with early stage breast cancer go on to develop MBC. Median survival is three years; annually, the disease takes 40,000 lives. 

As with primary breast cancer, treatment for mets can often be harsh and unforgiving.  But dealing with an incurable illness and the side effects of its treatment aren’t the only burden MBC patients have to bear. Many also have to educate others about their disease, explaining over and over that no, the scans and blood tests and treatments will never come to end. No, the metastasized breast cancer in their lungs is neither lung cancer nor linked to smoking. No, staying positive and “just fighting hard” isn’t going to beat back their late stage disease.

As one mets patient in this Living Beyond Breast Cancer video put it, “It’s almost like having another job … My wish would be that the larger support circle would just get it more.”

A disease no one ‘gets’

Sadly, people don’t “get” mets. In fact, a recent survey sponsored by Pfizer Oncology shows just how misunderstood it is. Sixty percent of the 2,000 people surveyed knew little to nothing about MBC while 72 percent believed advanced breast cancer was curable as long as it was diagnosed early. Even more disheartening, a full 50 percent thought breast cancer progressed because patients either didn’t take the right treatment or the right preventative measures.

“They’ve built an industry built on four words – early detection equals cure -- and that doesn’t even begin to define breast cancer,” said Schoger, who helped found Breast Cancer Social Media, a virtual community for breast cancer survivors, surgeons, oncologists and others. “Women are blamed for the fate of bad biology.”

The MBC Alliance, a consortium of 29 cancer organizations including the biggest names in breast cancer (think Avon, Komen, Susan Love, etc.), addressed this lack of understanding and support as well as what many patient advocates term the underfunding of MBC research in a recently published landmark report. 

“The dominance of the ‘breast cancer survivor’ identity masks the reality that patients treated for early stage breast cancer can experience metastatic recurrence … [anywhere from] a few months [to] 20 years or more after initial diagnosis,” the report states. “Public messaging about the ‘cure’ and survivorship is so pervasive that people diagnosed at Stage 4 with MBC can be stigmatized by the perception that they’ve failed to take care of themselves or undergo annual screening.”

‘You end up on Mars’
OncoDNA's insight:

A no-nonsense Texan of 60 years, Jody Schoger has a very no-nonsense way of educating people about her metastatic breast cancer.

“Someone will say, ‘When are you done with treatment?’ and I’ll tell them, ‘When I’m dead,’” said Schoger, a writer and cancer advocate who lives near Houston.  “So many people interpret survivorship as going across the board. That everybody survives cancer now. But everybody does not survive cancer.”

An estimated 155,000 plus women (and men) in the U.S. currently live with “mets,” Stage 4 breast cancer that’s traveled through the bloodstream to create tumors in the liver, lungs, brain, bones and/or other parts of the body. While treatable, metastatic breast cancer (MBC) is incurable. Between 20 and 30 percent of women with early stage breast cancer go on to develop MBC. Median survival is three years; annually, the disease takes 40,000 lives. 

As with primary breast cancer, treatment for mets can often be harsh and unforgiving.  But dealing with an incurable illness and the side effects of its treatment aren’t the only burden MBC patients have to bear. Many also have to educate others about their disease, explaining over and over that no, the scans and blood tests and treatments will never come to end. No, the metastasized breast cancer in their lungs is neither lung cancer nor linked to smoking. No, staying positive and “just fighting hard” isn’t going to beat back their late stage disease.

As one mets patient in this Living Beyond Breast Cancer video put it, “It’s almost like having another job … My wish would be that the larger support circle would just get it more.”

A disease no one ‘gets’

Sadly, people don’t “get” mets. In fact, a recent survey sponsored by Pfizer Oncology shows just how misunderstood it is. Sixty percent of the 2,000 people surveyed knew little to nothing about MBC while 72 percent believed advanced breast cancer was curable as long as it was diagnosed early. Even more disheartening, a full 50 percent thought breast cancer progressed because patients either didn’t take the right treatment or the right preventative measures.

“They’ve built an industry built on four words – early detection equals cure -- and that doesn’t even begin to define breast cancer,” said Schoger, who helped found Breast Cancer Social Media, a virtual community for breast cancer survivors, surgeons, oncologists and others. “Women are blamed for the fate of bad biology.”

The MBC Alliance, a consortium of 29 cancer organizations including the biggest names in breast cancer (think Avon, Komen, Susan Love, etc.), addressed this lack of understanding and support as well as what many patient advocates term the underfunding of MBC research in a recently published landmark report

“The dominance of the ‘breast cancer survivor’ identity masks the reality that patients treated for early stage breast cancer can experience metastatic recurrence … [anywhere from] a few months [to] 20 years or more after initial diagnosis,” the report states. “Public messaging about the ‘cure’ and survivorship is so pervasive that people diagnosed at Stage 4 with MBC can be stigmatized by the perception that they’ve failed to take care of themselves or undergo annual screening.”

‘You end up on Mars’


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The Role of Anti-PD-L1 Immunotherapy in Cancer

The Role of Anti-PD-L1 Immunotherapy in Cancer | Cancer Targeted Therapies | Scoop.it

Immunotherapy has become an increasingly appealing therapeutic strategy for patients with cancer, with many late-stage clinical trials demonstrating overall survival (OS) advantages in melanoma and castrationresistant prostate cancer. More recently, non-small cell lung cancer (NSCLC) has become a focus for the next generation of immune-based therapeutic strategies. Immunotherapy, in particular the use of monoclonal antibodies that block inhibitory immune checkpoint molecules and therefore enhance the immune response to tumors, has shown clinical promise in advanced solid tumors. The clinical rationale for targeting the PD-1/PD-L1 pathways will be reviewed in this supplement, including a comprehensive review of selected ongoing clinical trials to evaluate the potential of targeting immunotherapy in cancer drug development. Emerging clinical data discussed in this supplement suggest that targeting immunotherapy in cancer will become an integral part of the clinical management strategy for solid tumors.

Introduction

Cancer is traditionally treated with either conventional therapy (ie, chemotherapy or radiation therapy) or targeted drugs that directly kill tumor cells. While the number of patients who survive cancer has seen significant increases, the “war” rages on.1

More than a century ago, a series of primitive experiments hinted at the potential of harnessing the immune system to fight cancer.2 The immune system protects the body from foreign invading agents by recognizing “non-self” proteins (antigens) displayed on their surface that distinguish them from normal, healthy tissue. This subsequently initiates a protective response that neutralizes these organisms.3 William Coley was the first to draw a link between the immune system and cancer. He observed spontaneous remission in cancer patients following infection with a mixture of killed infectious agents, dubbed Coley’s toxins.2 Since then, a dyna mic and complex relationship between the immune system and cancer has been uncovered, and the concept of immunotherapy was born.

Cancer cells are normal cells that have acquired numerous hallmark abilities that allow them to become malignant; 4 thus, they are essentially “self”—part of the host. In spite of this, they often display unusual or inappropriate proteins on their cell surface that allow the immune system to identify them as “non-self”, and an antitumor immune response is often mounted. However, cancer cells have evolved a number of mechanisms to enable evasion of this immune response and render it ineffective. Typically, by the time a cancer becomes detectable, the balance of power between the immune system and the cancer has shifted in favor of the growing tumor, and a state of immune tolerance has been established. Immunotherapy refers to a diverse range of therapeutic approaches that aim to harness the immune system to re-establish a targeted antitumor immune response. The goal of cancer immunotherapy is to enable the patient’s immune system to specifically recognize and kill cancer cells.5-9

There are two distinct types of immunotherapy: passive immunotherapy uses components of the immune system to direct targeted cytotoxic activity against cancer cells, without necessarily initiating an immune response in the patient, while active immunotherapy actively triggers an endogenous immune response. Passive strategies include the use of the monoclonal antibodies (mAbs) produced by B cells in response to a specific antigen.6 The development of hybridoma technology in the 1970s and the identification of tumor-specific antigens permitted the pharmaceutical development of mAbs that could specifically target tumor cells for destruction by the immune system. Thus far, mAbs have been the biggest success story for immunotherapy; the top three best-selling anticancer drugs in 2012 were mAbs.10 Among them is rituximab (Rituxan, Genentech), which binds to the CD20 protein that is highly expressed on the surface of B cell malignancies such as non-Hodgkin’s lymphoma (NHL). Rituximab is approved by the FDA for the treatment of NHL and chronic lymphocytic leukemia (CLL) in combination with chemotherapy.11 Another important mAb is trastuzumab (Herceptin; Genentech), which revolutionized the treatment of HER2 (human epidermal growth factor receptor 2)-positive breast cancer by targeting the expression of HER2.12 - See more at: http://www.onclive.com/web-exclusives/The-Role-of-Anti-PD-L1-Immunotherapy-in-Cancer?__scoop_post=ee517f20-57ab-11e4-a86d-001018304b75&__scoop_topic=3545156#__scoop_post=ee517f20-57ab-11e4-a86d-001018304b75&__scoop_topic=3545156

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Krishan Maggon 's curator insight, October 20, 2014 3:54 AM

One of the best updated review of the current PD1/PDL1 immunotherapy.

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A New Target for Personalized Brain Cancer Treatment

A New Target for Personalized Brain Cancer Treatment | Cancer Targeted Therapies | Scoop.it
New findings could provide additional insight into the cause of glioblastoma and provide new options for personalized therapeutic treatments.
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