Merck’s Former Doctor Predicts Gardasil To Become The Greatest Medical Scandal Of All Time


dr-bernard-dalbergue
“It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine” –(source) Marica Angell. She is a physician and author, along with being the first woman to serve as editor-in-chief of The New England Journal of Medicine – regarded as one of the most prestigious peer-reviewed medical journals in the world.

Since the Food and Drug Administration (FDA) approved Merck & Co.’s Gardasil vaccine in 2006, it has been surrounded by tremendous amounts of information, controversy and misinformation. This controversy has garnered much attention as people become more aware of the importance of paying attention to what goes into their bodies. It’s imperative that one examines a large body of evidence before believing what is seen on TV or stated on a radio advertisement, and people are slowly starting to wake up to this fact.

“It is a vaccine that’s been highly marketed, the benefits are over-hyped, and the dangers are underestimated.” –  (Taken from the ONE MORE GIRL DOCUMENTARY) – Dr. Chris Shaw, Professor at the University of British Columbia, in the department of Neuroscience, Ophthalmology, and Visual Sciences.

Gardasil, also known as the Human papilloma virus (HPV) vaccine, is given as a series of three shots over 6 months to protect against HPV infection and its associated health problems. Two vaccines (Cervarix and Gardasil) are said to protect against cervical cancers in women. Gardasil is also said to protect against genital warts and cancers of the anus, vagina and vulva. Both vaccines are available for females, while only Gardasil is available for males.

The Centers For Disease Control (CDC) claims that the HPV vaccine offers the best protection to girls and boys who receive all three vaccine doses and have time to develop an immune response before being sexually active.  This is why it is recommended for children who have reached the age of 11 or 12.

There is a long list of educated people speaking out about this vaccine. This time around, it’s Dr. Bernard Dalbergue, a former pharmaceutical industry physician with Gardasil manufacturer Merck who has started to raise his voice against the HPV vaccine, along with the pharmaceutical industry as a whole. He joins a long list of experts from within the industry who have slammed the rampant manipulation and control of clinical research done by the pharmaceutical industry.

This quote is taken from an interview that happened in April of 2014, from an issue of the French magazine Principes de Santé (Health Principles):

“The full extent of the Gardasil scandal needs to be assessed: everyone knew when this vaccine was released on the American market that it would prove to be worthless.  Diane Harper, a major opinion leader in the United States, was one of the first to blow the whistle, pointing out the fraud and scam of it all.I predict that Gardasil will become the greatest medical scandal of all time because at some point in time, the evidence will add up to prove that this vaccine, technical and scientific feat that it may be, has absolutely no effect on cervical cancer and that all the very many adverse effects which destroy lives and even kill, serve no other purpose than to generate profit for the manufacturers. Gardasil is useless and costs a fortune!  In addition, decision-makers at all levels are aware of it! Cases of Guillain-Barré syndrome, paralysis of the lower limbs, vaccine-induced MS and vaccine-induced encephalitis can be found, whatever the vaccine.” (source) – Dr. Bernard Dalbergue

Dr. Dalbergue has also recently released a book titled “Omerta dans les labos pharmaceutiques: Confessions d’un medicine,” which goes into more detail about corruption in the medical/pharmaceutical industry. He also recently made an appearance on a popular radio show in France, you can watch here. Althought it’s in French, it’s nice to put a face to the name so that you can see he is real.

Scandal, misinformation, and data manipulation have become part and parcel of clinical research and pharmaceutical drug development. It is important that we realize this as fact and not hearsay; apart from whistle-blowers, there are numerous documents that illustrate this reality. One of the best examples (out of many) comes from Lucija Tomljenovic, PhD, from the Neural Dynamics Research Group in the Department of Ophthalmology and Visual Sciences at the University of British Columbia. In 2011 she obtained documents which reveal that vaccine manufacturers, pharmaceutical companies, and health authorities have known about the multiple dangers associated with vaccines but have chosen to withhold them from the public. The documents were obtained from the UK Department of Health (DH) and the Joint Committee on Vaccination and Immunization (JCVI), who advise the Secretaries of State for Health in the UK about diseases preventable through immunizations.

Another doctor making noise regarding the HPV vaccine is Dr. Diane Harper. Dr. Harper helped design and carry out the Phase II and Phase III safety and effectiveness studies to get Gardasil approved, and authored many of the published papers about it. She has been a paid speaker and consultant to Merck. It’s very unusual for a researcher to publicly criticize a medicine or vaccine she helped get approved, it is a credit to her character for doing so. It also says a lot that she agreed to participate in the ONE MORE GIRL documentary, which implies (I believe) there is a chance she resonates with the other information that’s stated in the documentary that she has not said publicly.

ONE MORE GIRL is an answer to Merck & Co’s One Less Girl marketing campaign for the HPV vaccine Gardasil. The parents who encouraged their daughters to get the HPV vaccine did so on the advice of their doctors, their government, and their belief in pharmaceutical industry. They were not “anti-vaccine,” they played by the rules, and now they are paying the price. It’s a documentary that has several experts from the industry, various doctors, and university researchers speaking out about the vaccine.

“They created a huge amount of fear in mothers, and appealed to mothers’ sense of duty to get them to get their daughters vaccinated” – Dr Diane Harper (source)

The above quote was taken from the film, and here is an excerpt of her raising some important things to consider regarding the vaccine.

Some Research

If we are talking about recent research regarding the HPV vaccine, a new review was just published  in the journal Autoimmunity Reviews titled, “On the relationship between human papilloma virus vaccine and autoimmune disease.” 

The authors of this study came to the same conclusion as Dr. Harper, a doctor that was directly involved with the clinical trials for the approval of the vaccine (mentioned earlier in the article). They concluded that:

“The decision to vaccinate with HPV vaccine is a personal decision, not one that must be made for public health. HPV is not a lethal disease in 95% of the infections; and the other 5% are detectable and treatable in the precancerous stage.” (If you are interested you can access the paper here)

They also listed several conditions in which HPV vaccination is most likely the culprit, having been linked to a variety of autoimmune diseases which include: Multiple sclerosis, Guillain-Barre syndrome, primary ovarian failure, and more.

The 2008 FDA Closing Statement on Gardasil reports that 73.3% of the ‘healthy’ girls who participated in the clinical trials developed ‘New Medical Conditions. The list below highlights some of the ‘New Medical Conditions’ reported in the 2008 FDA Closing Statement on Gardasil. (source)

    • Blood & Lymphatic System Disorders 2.9% = 1 in 34
    • Gastrointestinal Disorders 13.4% = 1 in 7
    • General & Administration Site Conditions 3.8% = 1 in 33
    • Immune System Disorders 2.4% =1 in 50
    • Infections & Infestations 52.9% = 1 in 2
    • Injury, Poisoning, & Procedural Complications 8.0% =1 in 12
    • Investigations 11.8% =1 in 9
    • Musculoskeletal & Connective Tissue Disorders 6.8% =1 in 14
    • Nervous System Disorders 9.4% = 1 in 10
    • Pregnancy, Puerperium & Perinatal Conditions 2.0% = 1 in 50
    • Psychiatric Disorders 4.4% =1 in 22
    • Renal Disorders 2.7% =1 in 37
    • Reproductive & Brest Disorders 24.8 % = 1 in 14
    • Respiratory, Thoracic & Mediastinal Disorders 5.5% = 1 in 18
    • Skin & Subcutaneous Tissue Disorders 7.4% = 1 in 13
    • Surgical Procedures = Appendectomy 10.2% = 1 in 10

A year ago the vaccine was taken off the recommended vaccine schedule in Japan due to it’s adverse effects. What’s even more concerning is the fact that today’s vaccine has twice the amount of aluminum in it.

Related CE Article:

This is what can happen to children who receive aluminum containing vaccines.

Another groundbreaking article titled “Quantifying the possible cross-reactivity  risk of an HPV16 vaccine, published in the Journal of Experimental Therapeutics and Oncology concluded that:

“The number of viral matches and their locations make the occurrence of side autoimmune cross-reactions in the human host following HPV16-based vaccination almost unavoidable.” (source)

The list is literally endless, and for the sake of not turning this article into an essay, I’ll stop here. Hopefully I’ve provided you with enough information to further your research if interested. If you want to look at more scientific data, you can check out:

Giant Database of Studies Regarding The Gardasil Vaccine.

Sources:

All other sources are linked throughout the article.

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964337/

http://www.greenmedinfo.com/anti-therapeutic-action/vaccination-hpv-gardisil

http://www.sciencedirect.com/science/article/pii/S1568997214000664

http://onemoregirlmovie.com/

http://www.cbsnews.com/news/gardasil-researcher-speaks-out/

 http://nsnbc.me/wp-content/uploads/2013/05/BSEM-2011.pdf

Giant Database of Studies Regarding The Gardasil Vaccine.

The Heart Consciousness – a Neurological Perspective


Heart Consciousness - a Neurological Perspective

 

During organ transplantation there have been numerous reports of emotions, memories and experiences being transferred along with the organ which is being transplanted, from the donor to the recipient.  Dr. Paul Pearsall has collected the cases of 73 heart transplant patients and 67 other organ transplant recipients and published them in his book, “The Hearts Code” (1). Here is a sample of a case that has been reported.

Transplant recipient develops desire for chicken nuggets and green peppers.

On May 29, 1988, an American woman named Claire Sylvia received a heart transplant at a hospital in Yale, Connecticut. She was told that her donor was an 18 year-old male from Maine who had just died in a motorcycle accident.

Soon after her operation, Sylvia declared that she felt like drinking beer, something she hadn’t particularly been fond of before. Later, she observed an uncontrollable urge to eat chicken nuggets and found herself drawn to visiting the popular chicken restaurant chain, KFC.  She also began craving green peppers which she hadn’t particularly liked before. She started behaving in an aggressive and impetuous manner following the surgery. Sylvia also began having recurring dreams about a mystery man named Tim, whom she felt was the organ donor.

She searched for obituaries in newspapers published from Maine and was able to identify the young man whose heart she had received. His name had indeed been Tim. After visiting Tim’s family, she discovered that he used to love chicken nuggets, green peppers and beer. These experiences are documented in her book, A Change of Heart: A Memoir  (2).

The Heart Brain

In 1974, the French researchers Gahery and Vigier, working with cats, stimulated the vagus nerve (which carries many of the signals from the heart to the brain) and found that the brain’s electrical response was reduced to about half its normal rate when stimulating the vagus nerve (3).  The heart appeared to be sending meaningful messages to the brain that it not only understood, but also obeyed (4).  Later, neurophysiologists discovered a neural pathway and mechanism whereby input from the heart to the brain could inhibit or facilitate the brain’s electrical activity (5).

Dr. Armour introduced the idea of functional “heart brain.” His research revealed that the heart has a complex intrinsic nervous system that is sufficiently refined to qualify as a “little brain” in its own right, due to its independent existence.

The heart’s nervous system contains around 40,000 neurons, called sensory neurites. The heart’s brain is an intricate network of several types of neurons, neurotransmitters, proteins and support cells similar to those found in the brain proper. Its elaborate circuitry enables it to act independently of the cranial brain to learn, remember, and even feel and sense (6).

Information from the heart, including feeling sensations, is sent to the brain through several afferents. These afferent nerve pathways enter the brain at the area of the medulla, and cascade up into the higher centers of the brain, where they may influence perception, decision making and other cognitive processes (7).

When heart rhythm patterns are coherent the neural information sent to the brain facilitates cortical function. This effect is often experienced as heightened mental clarity, improved decision making and increased creativity. Additionally, coherent input from the heart tends to facilitate the experience of positive feeling states (8).

States of increased heart rhythm coherence are associated with improvements in cognitive performance (9). The brain’s alpha wave activity is synchronized to the cardiac cycle. During states of high heart rhythm coherence, alpha wave synchronization to the heart’s activity significantly increases (10).

The heart’s afferent neurological signals directly affect activity in the amygdala and associated nuclei, an important emotional processing center in the brain. The amygdala is the key brain center that coordinates behavioral, immunological, and neuroendocrine responses to environmental threats. It compares incoming emotional signals with stored emotional memories, and accordingly makes instantaneous decisions about the level of perceived threat.

Due to its extensive connections to the limbic system, it is able to take over the neural pathways, activating the autonomic nervous system and emotional response before the higher brain centers receive the sensory information (11).

The heart communicates information to the brain and throughout the body via electromagnetic field interactions. The heart generates the body’s most powerful and most extensive rhythmic electromagnetic field. The heart’s magnetic component is about 500 times stronger than the brain’s magnetic field and can be detected several feet away from the body.

It was proposed that, this heart field acts as a carrier wave for information that provides a global synchronizing signal for the entire body (12). There is now evidence that an influential electromagnetic communication system operates just below our conscious awareness. Energetic interactions possibly contribute to the magnetic attractions or repulsions that occur between individuals, and also affect social relationships.

It was also found that one person’s brain waves can synchronize to another person’s heart (13). When people touch or are in proximity one person’s heartbeat signal is registered in the other person’s brainwaves (14). When two people are at a conversational distance, the electromagnetic signal generated by one person’s heart can influence the other person’s brain rhythms.

When an individual is generating a coherent heart rhythm, synchronization between that individual’s brainwaves and another person’s heart-beat is more likely to occur (15).

Individuals capable of generating high ratios of heart coherence were able to alter DNA conformation according to their intention. Intending to denature (un-wind) or renature (wind) the DNA had corresponding effects on the UV spectra (16). As people learn to sustain heart-focused positive feeling states, the brain can be brought into entrainment with the heart (17). The conclusion is the need of pointing to the heart as the center of consciousness.

Air Force Wants to Fire Lasers from Aircraft by 2023


The Air Force plans to be able to incinerate targets such as incoming missiles with laser weapons mounted on C-17s by 2023 as part of a directed energy developmental effort, service official said.

Graphic representation of the Air Force’s hopes for its aircraft laser program. (Courtesy of the Air Force)

The High Energy Laser, or HEL, is being tested by the Air Force Directed Energy Directorate, Kirtland Air Force Base, N.M. Ground tests are slated for later this year as part of a plan to precede air-launched laser weapons firing evaluations, Mica Endsley, Air Force Chief Scientist, told Military.com in an interview.

The first ever ground test of the weapon is slated to take place at White Sands Missile Range, N.M., said Othana Zuch, an Air Force spokeswoman.

Service officials are working on a solid-state laser guidance mechanism and focus so the weapon can stay on track on a particular target.

“We’re working on maturing a lot of those kinds of technologies,” Endsley said. “We will be transitioning into airborne platforms to get them ready to go into a program of record by 2023.”

Endsley added that the Air Force plans to begin firing laser weapons from larger platforms such as C-17s until the technological miniaturization efforts can configure the weapon to fire from fighter jets such as an F-15, F-16 or F-35.

The Air Force is interested in firing the weapon from sub-sonic, transonic, and supersonic platforms, Zuch added.

Aircraft-launched laser weapons could eventually be engineered for a wide range of potential uses including air-to-air combat, close-air-support, counter-UAS, counter-boat, ground attack and even missile defense, Air Force official said.

“The application will be things like being able to defeat an incoming missile for example, so that as opposed to a kinetic kill that would blow up that weapon the laser will basically melt through the metal and electronics using these non-kinetic techniques,” Endsley added.

The first airborne tests are expected to take place by 2021, Zuch added.

The developmental efforts are focused in increasing the power, precision and guidance of existing laser weapon applications, Endsley added.

“We want to put those capabilities in to a system that will move from something like 10 kilowatts up to 100 kilowatts — up to greater power.  We will work on things like guidance, control and precision,” she said.

Energy to fire aircraft lasers is engineered to come from on-board jet fuel to potentially enable thousands of shots, Endsley added.

“The real advantage is it would have a much more extended magazine. Today’s have five, six, seven missiles. With a directed energy weapon you could have thousands of shots with a gallon of gasoline – a gallon of jet fuel,” she said.

Of course, this isn’t the first time the Air Force has tried to mount a laser to an aircraft. The service tried to design an aircraft with a laser in the nose cone for missile defense purposes with a different style laser.

The Airborne Laser program featured a megawatt-class chemical oxygen iodine laser. It was tested in the nose cone of a Boeing 747-400 Freighter. Air Force officials say they are now benefiting from the technological efforts of  its previous ABL program.

However, Defense Secretary Robert Gates killed the program in 2009 when he said it was unaffordable and questioned if it would ever be feasible.

“The ABL program has significant affordability and technology problems, and the program’s proposed operational role is highly questionable,” he said in 2009 when he announced the end of DoD funding for the program.

Coffee could reduce risk of erectile dysfunction


Coffee perks millions of Americans up each morning, and a new study finds it might help keep men’s sex lives percolating, too.

The study, from the University of Texas Health Science Center at Houston, found that men who consume more caffeine each day had a lower risk of erectile dysfunction. The exception? Men with diabetes — for them, extra caffeine didn’t lower their odds for impotence, the researchers said.

“Even though we saw a reduction in the prevalence of erectile dysfunction with men who were obese, overweight and hypertensive, that was not true of men with diabetes. Diabetes is one of the strongest risk factors for erectile dysfunction, so this was not surprising,” lead author Dr. David Lopez, assistant professor at UTHealth School of Public Health, said in a university news release.

The study couldn’t prove cause-and-effect, but one expert said the findings are in line with current research.

“These findings also support the latest U.S. Dietary Guidelines Advisory Committee position that drinking three to five cups a day reduces the risk of type 2 diabetes and heart disease; two conditions that are well established as significant risk factors for erectile dysfunction,” said Dr. Natan Bar-Chama, director of Male Reproductive Medicine at the Mount Sinai Hospital in New York City.

In the study, Lopez and colleagues looked at data on more than 3,700 men tracked by the U.S. National Health and Nutrition Examination Survey. The men answered questionnaires asking them to recall their caffeine intake from the prior 24 hours.

The amount of caffeine that appeared to reduce the risk of impotence was equal totwo to three cups of coffee a day, the researchers said.

Compared to men in the study who consumed zero to 7 milligrams of caffeine a day, men who consumed 85 to 170 milligrams of caffeine a day were 42 percent less likely to report erectile dysfunction, and those who consumed 171 to 303 milligrams of caffeine a day were 39 percent less likely to report the condition, the Texas team said.

Caffeine sources in the study included beverages such as coffee, tea, soda and sports drinks.

The study authors believe that caffeine may help thwart impotence because it relaxes certain arteries and muscles in the penis, improving blood flow and the ability to have an erection.

Another expert agreed. “More research is needed, but what scientists think is happening here is that coffee and caffeine are causing cavernous smooth muscle tissue (found in the penis) to relax, allowing more blood flow to the area and leading to improved erectile function,” said Dr. David Samadi, chair of urology at Lenox Hill Hospital in New York City.

The study was published online recently in the journal PLOS One.

According to background information in the study, erectile dysfunction affects more than 18 percent of American men 20 and older

NSCLC immunotherapy coming of age.


Following the success of immune checkpoint inhibitors such as programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors in advanced melanoma, these agents are now emerging as effective treatments for non-small-cell lung cancer (NSCLC).

“This year, nivolumab became the first PD-1 inhibitor to receive US FDA approval for advanced NSCLC that has progressed on platinum-based chemotherapy,” said Dr. Solange Peters of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, at the European Lung Cancer Conference (ELCC) 2015 held recently in Geneva, Switzerland.

“In a phase III trial of 272 patients, nivolumab reduced mortality by 41 percent and prolonged survival by 3.2 months vs docetaxel,” She continued. [US FDA press release, 4 March 2015] “In an earlier phase II trial, single-agent nivolumab achieved a 15 percent response rate in heavily pretreated squamous cell NSCLC.”

Next in line is likely to be pembrolizumab, having shown an overall response rate of 45.2 percent in patients with ≥50 percent of tumour cells positive for PD-L1 expression. [N Engl J Med 2015, doi: 10.1056/NEJMoa1501824]

“These drugs as well as a number of other agents, such as ipilimumab and tremelimumab, and the PD-L1 inhibitors MPDL3280A, MEDI4736 and BMS936559, are also being evaluated in phase II/III trials with very encouraging results. Given the huge lung cancer market, the pharmaceutical companies are in a tight race,” she added.

Despite the early stage, some experts are now advocating immunotherapy as first-line treatment. “PD-1/PD-L1 inhibitors have demonstrated better clinical outcomes than chemotherapy, with a 15 percent increase in response rate and 2-month longer progression-free survival. Importantly, immunotherapy elicits a fast and durable response and is less toxic,” argued Dr. Jean-Charles Soria of the Institut Gustav Roussy, Villejuif, France, at a debate session. “For these reasons, it’s a good first-line alternative for advanced nononcogene-addicted NSCLC.”

The opponent, Dr. Kenneth O’Byrne of Queensland University of Technology in Brisbane, Australia, claimed, however, that the enthusiasm is premature and phase III data are needed to establish immunotherapy’s role in the first-line setting.

Despite the excitement, many challenges remain with immunotherapy, including side effects (diarrhoea, colitis, fatigue and pneumonitis) and pseudo progression, which should be considered when assessing patient response. Another drawback is the lack of a suitable biomarker. “PD -L1 expression in tumour cells is of limited value in predicting activity, as some patients with weak expression also respond, and could benefit from immunotherapy,” noted Peters. “The criteria for patient selection should be refined, as patient and tumour characteristics, including smoking status, previous therapy, histology and mutations, have been associated with responses to immunotherapy.”

The combination of immunotherapy with other treatment modalities such as chemotherapy, targeted therapy, radiotherapy or another immunotherapy is also being explored in many trials, according to Dr. Martin Reck of the Lung Clinic Grosshansdorf, Germany. “There are promising data but also conflicting results. Clinical development has somewhat overtaken the science behind. Proper translational research will be crucial and we should never forget safety when dealing with the powerful immune system,” he said.

Circulating tumour DNA helps detect EGFR mutations


While biopsy remains the gold standard for EGFR mutation testing in patients with advanced non-small-cell lung cancer (NSCLC), circulating tumour-derived DNA (ctDNA) may provide a more feasible methodology, according to studies presented at the European Lung Cancer Conference (ELCC) 2015 held in Geneva, Switzerland.

“We were looking for a valid test that can identify an EGFR mutation when the tumour is not accessible for bronchoscopy or CT-guided biopsy, and that’s in agreement with the gold standard tissue test,” said Dr. Martin Reck from the Lung Clinic Grosshansdorf, Germany.

Reck reported data from the real-world ASSESS study, which compared tumour biopsy with plasma ctDNA in 1,162 matching samples from European and Japanese patients. “Mutation status showed a high 89 percent concordance between the two methods,” he said. “The sensitivity of the plasma test was 46 percent, specificity was 97 percent, and positive predictive value [PPV] 78 percent.” [ELCC 2015, abstract 35O_PR]

He noted that use of a highly sensitive DNA sequencing methodology and identical methods for tissue and plasma testing in a subset of patients further increased sensitivity to 72 percent, specificity to 99 percent and PPV to 94 percent.

“While improvements are still required in mutation analysis practices of both tissue/cytology and plasma samples, our data show that plasma ctDNA may be a feasible, suitable sample for EGFR mutation analysis,” he suggested. “It is important to use robust and sensitive methodologies to ensure patients receive appropriate treatment to address the molecular features of their disease.”

Another study reported the extraction of urine ctDNA to test for EGFR T790M mutation — a hallmark of disease progression in advanced NSCLC that is useful for patient monitoring. [ELCC 2015, abstract 36O]

The investigators obtained urine samples from patients who progressed on erlotinib and were confirmed to have EGFR T790M mutation by a tumour biopsy test. “EGFR T790M status was analyzed by a sensitive assay that had a lower limit of detection of 2 copies in a background of 20,000 copies of wild-type DNA,” explained Dr. Hatim Husain from the University of California, San Diego, CA, US.

Using this assay, they detected T790M mutation in 10 out of 10 confirmed EGFR T790M-positive patients (sensitivity, 100 percent). In addition, three patients with negative tissue testing results tested positive by urine analysis. EGFR T790M mutation was detected as early as 3.5 months prior to radiographic progression on first-line EGFR tyrosine kinase inhibitor (TKI) therapy, identifying five patients who may be eligible for second-line EGFR TKI treatment due to emergence of T790M mutation.

“This method, combining the extraction of urine ctDNA with an ultra-sensitive next-generation sequencing and mutation enrichment technology, has the advantage of urine as ctDNA source, potentially enabling dynamic monitoring of EGFR TKI therapy response from a completely noninvasive sample,” concluded Husain.

BRAF inhibitors promising in lung adenocarcinoma


The BRAF inhibitors vemurafenib and dabrafenib, currently approved for use in advanced melanoma, are also effective in a subset of lung adenocarcinoma patients with BRAF mutations, according to a retrospective European trial presented at the European Lung Cancer Conference (ELCC) held in Geneva, Switzerland.

In the EURAF cohort study, researchers reviewed data of 35 patients with BRAF mutations who were treated with BRAF inhibitors (29 had BRAF V600E mutation; 6 had other BRAF mutations). Thirty-one patients received one BRAF inhibitor and four patients received two BRAF inhibitors. Altogether, 28 patients received vemurafenib, 10 received dabrafenib, and one received sorafenib. [ELCC 2015, abstract 980_PR]

“Best response by RECIST [Response Evaluation Criteria In Solid Tumours] was available for 36 of the 39 BRAF inhibitor therapies. Overall response rate was 53 percent, including 6 percent complete response, 47 percent partial response, 36 percent stable disease, and 11 percent disease progression. No unexpected toxicities were reported,” said Dr. Oliver Gautschi from Lucern Cantonal Hospital, Switzerland, who presented the results. “These data support BRAF testing in advanced lung adenocarcinoma, and BRAF inhibitor therapy in patients with V600E mutation.”

Commenting on the findings, Dr. David Planchard of the Institut Gustave Roussy in Villejuif, France, noted that only about 2 percent of lung adenocarcinomas harbour BRAF mutations. “Because of the low frequency of BRAF mutations in lung cancer, it is unlikely we will have randomized phase III trials in this population. The results of this study add to growing support for the approval of BRAF inhibitors for use in lung cancer.”

Ongoing studies are evaluating BRAF inhibitors in combination with other therapies and potential drug resistance mechanisms in this population.

PD-1 inhibitors surpass ipilimumab in advanced melanoma


Programmed cell death 1 (PD-1) inhibitors such as pembrolizumab and nivolumab, as monotherapy or in combination with ipilimumab, are better first-line therapies than ipilimumab alone in patients with advanced melanoma, data presented at the American Association for Cancer Research (AACR) 2015 Annual Meeting have shown.

In the phase III KEYNOTE-006 trial (n=834; 65.8 percent previously untreated), pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS) and response rates (RRs) vs ipilimumab, an inhibitor of cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) that is currently a standard first-line therapy for advanced melanoma. [N Engl J Med 2015, doi: 10.1056/NEJMoa1503093]

At 6 months, estimated PFS rates were 47.3 percent for pembrolizumab 10 mg/kg every 2 weeks and 46.4 percent for pembrolizumab 10 mg/kg every 3 weeks, compared with 26.5 percent for ipilimumab (3 mg/kg, 4 doses every 3 weeks) (hazard ratio [HR], 0.58; p<0.001).

“At 12 months, estimated OS rates were 74.1 percent for pembrolizumab every 2 weeks [HR, 0.63; p=0.0005] and 68.4 percent for pembrolizumab every 3 weeks [HR, 0.69; p=0.0036], vs 58.2 percent for ipilimumab,” reported lead author Dr. Antoni Ribas of the University of California, Los Angeles, CA, US.

RRs were also higher with pembrolizumab (33.7 percent for 2-weekly dosing, 32.9 percent for 3-weekly dosing) vs ipilimumab (11.9 percent; p<0.001).

Treatment-related grade 3-5 adverse events (AEs) were less common with pembrolizumab (13.3 and 10.1 percent for 2-weekly and 3-weekly dosing, respectively) than ipilimumab (19.9 percent).

“These results exceeded our expectations of the benefit of pembrolizumab over ipilimumab,” said Ribas. “The data will change the paradigm of treatment of advanced melanoma.”

Nivolumab, when used in combination with ipilimumab, also showed significant benefits over ipilimumab in patients with previously untreated advanced melanoma.

In a phase II trial of 142 patients, PFS and objective response rate (ORR) were significantly improved with the nivolumab/ipilimumab combination vs ipilimumab alone. [N Engl J Med 2015, doi: 10.1056/NEJMoa1414428]

“Among 109 patients with BRAF wild-type tumours, median PFS was not reached in the combination therapy arm vs 4.4 months with ipilimumab monotherapy [HR, 0.40; p<0.001],” reported lead investigator Dr. Stephen Hodi of the Dana-Farber Cancer Institute in Boston, MA, US.

ORR was 61 percent with combination therapy vs 11 percent with ipilimumab monotherapy (p<0.001). “Importantly, 22 percent of patients achieved complete response with the combination regimen,” said Hodi. “There were no complete responses with ipilimumab monotherapy.”

The investigators reported similar results for PFS and ORR in the 33 patients with BRAF V600 mutation-positive tumours. Again, 22 percent of patients achieved complete response with combination therapy.

However, the combination regimen was associated with higher rates of grade 3/4 drug-related AEs (54 percent vs 24 percent for ipilimumab monotherapy).

Pembrolizumab and nivolumab are currently approved by the US FDA for treatment of unresectable or metastatic melanoma that progressed after treatment with ipilimumab or a BRAF inhibitor.

Biomarkers may predict olaparib efficacy in advanced prostate cancer


prostate cancer

Genomic defects in DNA repair genes may predict response to olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC), a study presented at the American Association for Cancer Research (AACR) 2015 Annual Meeting has shown.

Among 49 patients with mCRPC who received olaparib in the phase II TOPARP-A study, 16 responded, giving an overall response rate of 32.7 percent. [AACR 2015, abstract CT322]

“Patients with homozygous deletions and/or putatively deleterious mutations in DNA repair genes were more likely to respond to olaparib,” reported Dr. Joaquin Mateo of the Institute for Cancer Research and Royal Marsden NHS Foundation Trust, London, UK. “The majority of these genomic defects occurred in BRCA2 and ATM, but biallelic loss of other relevant genes, including members of the Fanconi Anaemia complementation group and CHEK2, were also found.”

Of 15 patients with these genomic defects, 13 (86.7 percent) responded to olaparib, including all seven patients with BRCA2 loss and four of five patients with ATM truncating mutations.

“The specificity of the biomarker suite was 94 percent,” said Mateo. “Our findings offer a possibility for the very first molecular treatment stratification of advanced prostate cancer.”

“Olaparib showed durable anti-tumour activity in our heavily-pretreated population of mCRPC patients,” he added. “All study patients had received prior docetaxel therapy, 96 percent had received prior abiraterone, and 58 percent had received prior cabazitaxel. Of the 16 patients who responded to olaparib, 11 and four had been on olaparib therapy for >6 and >12 months, respectively.”

Antibiotics back as alternative for appendicitis


Every year, 300,000 Americans with appendicitis are rushed into emergency surgery. Most think that if the appendix is not immediately removed, it will burst -with potentially fatal consequences.But now some doctors say there may another option: antibiotics.

Five small studies from Europe, involving a total of 1,000 patients, indicate that antibiotics can cure some patients with appendicitis; about 70% of whom took the pills did not require surgery . Those who wound up having an appendectomy after trying antibiotics first did not face any more complications than those who had surgery immediately .

“These studies seem to indicate that antibiotics can cure appendicitis in many patients,” said Dr David Talan, a specialist in emergency medicine and infectious diseases at the University of California, Los Angeles.”You at least have the chance of avoiding surgery altogether.”
antibiotics

Talan and others are planning a large clinical trial to compare people with appendicitis who receive antibiotics or surgery.

In preparation, Talan and his colleague Dr David Flum, a surgeon at the University of Washington, spent much of the past year asking patients if they would be interested in participating. Nearly half said yes. In another survey , nearly three-quarters of those who had already had an appendectomy said they would have preferred to try antibiotics first. By suggesting an antibiotic alternative, the researchers are bucking longstanding medical tradition.

Surgical treatment for appendicitis began in the 1880s, when surgery itself was something of a new idea. As surgery and anesthesia improved, however, the appendectomy became the treatment of choice. According to the medical thinking of the day , it made sense. But surprising as antibiotics might seem, this is not the first time they have emerged as a possible alternative.

When antibiotics became available in the 1940s and ’50s, doctors in England began giving them to patients with appendicitis, reporting excellent results.During the Cold War, when American sailors spent six months or more on nuclear submarines prohibited from surfacing, those who developed appendicitis were given antibiotics. “Those submariners did great and no deaths or complications were reported,” Flum said. But that did not put a dint in the perception of surgery as the top choice.

The planned clinical trial will attempt to answer important questions. Are antibiotics as good as surgery in curing appendicitis? Could they do so at less cost, avoiding a hospitalization afterward? It’s even not clear how the drugs should be administered.

Giana Davidson, surgeon at University of Washington, said, “We don’t have the answers to questions that matter to patients.What are the chances of it coming back? I just have a lot of hesitation to go away from a 30-minute operation that cures them for the rest of their lives.”