FDA

Why the FDA Wants More Control over Some Lab Tests

The FDA finds that many so-called laboratory-derived tests may actually harm patients

By Charles Schmidt | Scientific American December 2016 Issue

Every year in the U.S., doctor’s offices and hospitals order billions of laboratory tests to measure everything from cholesterol levels in the blood to the presence of a gene thought to increase the risk of developing Alzheimer’s disease. Physicians and patients typically assume that they can trust the results of these tests. And most of the time they can. But not all lab tests are equally reliable, and faulty ones can have serious consequences. Sometimes they fail to detect life-threatening conditions. Other times they indicate a problem that does not exist, which can lead to unneeded, perhaps even dangerous treatments.

Through a quirk of regulatory history, many such tests are not subject to the same medical standards as other tools used to identify risk for disease or to definitively diagnose a condition. These are called lab-developed tests, or LDTs, defined as tests that are manufactured and interpreted by the same individual lab that designed them—in contrast to, say, a quick strep test meant to be used and understood by a wide variety of personnel in doctor’s offices everywhere. Most people first encounter an LDT during a checkup when the physician is faced with a diagnostic dilemma that cannot be resolved by widely available blood tests.

The trouble is, experts believe many of these tests are not useful, and some may even cause harm by convincing too many people that they have a rare illness when they do not, diagnosing them with a condition that has so far not been shown to be harmful or reassuring them that they are healthy when in fact there is no scientifically credible way to know if that is indeed the case. “We tend to think of lab tests as being the ultimate truth,” says Ramy Arnaout, an assistant professor of pathology at Harvard Medical School. “But no test is 100 percent accurate, and some of these LDTs aren’t medically useful at all.”

The U.S. Food and Drug Administration is now taking steps to restore confidence in the reliability of lab-developed tests. In 2014 the agency released proposed guidelines that will subject the measures, for the first time, to federal oversight—including having to submit evidence of efficacy to it before the tests may be marketed. Although the FDA would not comment for this story, several industry sources believe the final rulings may begin taking effect soon, much to the chagrin of some lab directors who say that the requirements could boost costs and hinder medical practice.

Widening Loophole

Twenty-five years ago LDTs played too small a role in medical practice for the FDA to pay them much attention. Only a few—most notably Pap smears for the detection of cervical cancer—were widely used. FDA officials adopted a policy of “enforcement discretion,” which meant they pretty much left LDTs alone while they focused on tools with an apparently greater potential for harm, such as malfunctioning pacemakers.

After researchers developed new genetic engineering techniques in the 1990s, however, the possibilities for LDTs expanded dramatically. Whereas previous generations of LDTs looked for a handful of unusual proteins, for example, some of the newly emerging genetic tests could sort through any number of the three billion base pairs, or letters, of the DNA alphabet found in the human genome, looking for abnormalities related to disease. In addition, testing became automated, making LDTs increasingly easier to design and use.

The improved technology led to an enormous rise in the number and variety of LDTs that came to market. By some estimates, about 11,000 labs now offer between 60,000 and 100,000 of them; no one knows precisely how many because, of course, these tests do not have to be registered anywhere.

Under current federal regulations, LDTs enjoy a big loophole, which means they do not have to be evaluated for their medical usefulness. Nor are they required to have research about them made public. The lab that created them does need to meet certain fundamental standards of scientific practice. But the FDA does not vet the tests either before or after doctors can start ordering them for patients, as it does for most prescription drugs or medical devices.

This loophole means that companies ranging from small start-ups offering just one or two tests to much larger diagnostic labs that offer thousands of tests can develop and charge for new LDTs much more easily than they can for most other categories of medical products. With the rise in the number of tests has come a series of reports showing that certain ones have already hurt people by delivering misleading results.

Clinical Validity

The FDA has cited 20 different types of LDTs as especially troubling, including Lyme disease and whooping cough tests that regularly give wrong answers and LDTs that purport to determine a woman’s risk for ovarian cancer such as by measuring the presence of the protein CA 125 in the blood. In September the agency concluded that screening measures for this protein offered “no proven benefit” and warned physicians against recommending or using them.

Many of the tests that have raised the FDA’s ire may indeed measure what they claim to measure. The problem is that the measured substance may not be a good indicator of a specific medical problem. In the case of the ovarian cancer tests, for instance, high levels of CA 125, which is made in the ovaries, should in theory signify the presence of extra ovarian cells—in other words, the presence of a tumor. In reality, it turns out that many women with high levels of CA 125 do not have ovarian cancer, and, conversely, many women with cancer do not have high levels of CA 125. Thus, measures of CA 125 cannot be trusted to give an accurate diagnosis of cancer—and yet a number of women who tested positive apparently feared the possibility of cancer so much that they decided to have their healthy ovaries removed anyway.

One way that investigators determine whether a medical test should be used as a guide to a patient’s condition is by applying a somewhat obscure statistical ratio called a positive predictive value, or PPV. This measure takes into account just how common a condition might be in a given group of people.

Why such a consideration would be important in determining a test’s usefulness may be best understood by analogy. If you drop a baited hook into a barrel full of fish, the chances that a tug on the line means that you have caught a fish are pretty high. On the other hand, dropping the same baited hook into a freshwater lake that has not been stocked with fish makes it much less likely that any given tug on the line represents a fish, as opposed to, say, a tree snag. Because the barrel contains many more fish for a given volume of water than the lake does, a tug in the container has a PPV close to 100 percent, whereas that of a tug in an unstocked lake is much less than 100 percent.

This crucial statistical distinction explains the problem the FDA has with one current ovarian screening test, which its developer claimed had a PPV of 99.3 percent. Closer analysis by independent biostatisticians revealed, however, that the value was calculated on the basis of a single experiment in which half the patients were already known to have ovarian cancer—a highly selected group that is the medical equivalent of a stocked pond.

When the researchers recalculated the PPV using ovarian cancer’s true frequency in the general U.S. population of one case for every 2,500 postmenopausal women, the PPV plummeted to just 6.5 percent. In other words, only one in every 15 patients who received a positive result from this malignancy test would have actually had ovarian cancer. The other 14 would, if they had relied on this test alone, very likely have undergone unnecessary operations to remove their otherwise healthy ovaries because they would have mistakenly believed they had a 99.3 percent chance of having cancer.

Changing Focus

Because the FDA does not have the resources to oversee all the LDTs that have come to market in recent years, the agency plans to divide them into three categories, based on the likelihood that a misleading or incorrect result from a particular test could cause substantial harm. Under the new guidelines, LDTs would be considered high risk if inaccurate results could lead to death or prolonged disabilities. Such tests would come under the greatest inspection, information about them would need to be entered in a national database, and manufacturers would have to prove their safety and efficacy to the FDA before they could be sold. “Basically, the FDA wants to see the supporting evidence before it allows a high-risk LDT to go out on the market,” says Joshua Sharfstein, a physician and professor at the Johns Hopkins Bloomberg School of Public Health.

Even this targeted approach worries many industry leaders and some professional medical societies, including the American Medical Association. “It really depends on how the FDA chooses to define high risk, and that currently isn’t clear,” says Curtis Hanson, chief medical officer at Mayo Medical Laboratories in Rochester, Minn., which conducts 25 million lab tests a year. “High-risk tests could amount to between 1 and 10 percent of LDTs on the market today. How is the FDA going to review and find the rare cases where you have problems and do that in an efficient way that doesn’t slow progress?”

For patients and their physicians, the question is much more basic. Why should they ever have to wonder whether a commercially available medical test does more harm than good?

This article was originally published with the title “When Medical Tests Mislead”

 

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2016|Oral Cancer News|

Expert Asserts Pembrolizumab to Play Important Role in Head and Neck Cancer Treatment

Source: www.targetedonc.com
Author: Laura Panjwani

Joshua-Bauml

The FDA approval of pembrolizumab (Keytruda) as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in August 2016 was extremely significant for this patient population, which previously had limited options following progression on a platinum-based chemotherapy.

The approval was based on the phase Ib KEYNOTE-012 study, which demonstrated that pembrolizumab had an overall response rate (ORR) of 18% and a stable disease rate of 17% in patients with recurrent/metastatic HNSCC.

Several other studies are further evaluating the immunotherapy agent in HNSCC.Preliminary results of the phase II KEYNOTE-055 study—which included 92 evaluable patients who received pembrolizumab after failing platinum and cetuximab therapies—were presented at the 2016 ASCO Annual Meeting.

In an interview with Targeted Oncology, lead study author Joshua M. Bauml, MD, an assistant professor of Medicine, Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center, discusses the impact of pembrolizumab’s success in HNSCC, the results of the KEYNOTE-055 study, and what he sees on the horizon for the PD-1 inhibitor in this field.

TARGETED ONCOLOGY: What role do you envision pembrolizumab having in this patient population?

Baumi: It is going to play a critical role in head and neck cancer. The other agents that are available have limited efficacy, and are associated with significant toxicities. This is a clear improvement for our patient population with limited options.

TARGETED ONCOLOGY: What were the key takeaways from KEYNOTE-055? Baumi: Patients with recurrent/metastatic head and neck cancer that is refractory to both platinum-based therapy and cetuximab (Erbitux) really have very few options. The historical reference population we usually use is patients treated with methotrexate, which has a response rate of 5% and an overall survival (OS) of only about 6 months. There is a really great need for this. For pembrolizumab, which is an anti–PD-L1 agent, there is biologic rationale to think that it would be active in this patient population. PD-L1 and PD-L2 are unregulated in head and neck cancer.

What KEYNOTE-055 did is really try and create a homogenous patient population. Rather than a large phase I study, here are patients all who have failed both platinum-based therapy and cetuximab. We have really identified the sickest patient population.

What we are able to show in this study was that the drug was well tolerated and it has a response rate of 17% to 18%, which compares favorably for the 5% seen with the prior data with methotrexate. The OS rate was 8 months, which again compares very favorably to the 6 months seen with methotrexate. This was true, even though 85% of patients had received at least 2 prior treatments for head and neck cancer.

TARGETED ONCOLOGY: What did this study tell us about the safety of pembrolizumab in head and neck cancer?

Baumi: The rate of grade 3 through 5 treatment-related adverse events was 12% in our study. Nearly all of the side effects are what you would expect with pembrolizumab; those have been reported in multiple other studies. There was 1 treatment-related death due to pneumonitis, which is a rare side effect of this class of drugs.

Outside of that, it was a really well-tolerated agent. The fact that if you compared grade 3 through 5 toxicities of 12% with cytotoxic chemotherapy, this is a very well-tolerated agent.

TARGETED ONCOLOGY: How common is it for patients to fail both platinum-based therapy and cetuximab?

Baumi: Any patient who has recurrent or metastatic head and neck cancer is going to go through these agents if they survive long enough to get them. Basically, we know that these are the limited tools in our toolbox. We have platinum, we have cetuximab, and then we are really out of options. Many patients have received cetuximab in the locally advanced setting and so we have already lost one of our active treatments. This affects a lot of people.

TARGETED ONCOLOGY: What is next for pembrolizumab in head and neck cancer?

Baumi: There are currently phase III studies evaluating pembrolizumab in head and neck cancer both in combination with and versus traditional cytotoxic chemotherapy to see if we can move up the treatment earlier for patients. The key difference between pembrolizumab and cytotoxics is beyond the improved safety profile. However, we have durable responses; 75% of those patients who responded are still responding to this day. That is really not something that we see.

TARGETED ONCOLOGY: What are the biggest questions that remain regarding the treatment of patients with metastatic head and neck cancer?

Baumi: One of the key questions that relates to immunotherapy—and this covers all tumors—is trying to identify who the 20% of patients are that will respond. Eighty percent of our patients are not responding to our therapies.

Identifying a biomarker to enrich this patient population is very critical. Right now, I would not select patients for pembrolizumab by virtue of PD-L1 status because there were responses in the PD-L1–negative cohorts.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

September, 2016|Oral Cancer News|

Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Source: www.onclive.com
Author: Laura Panjwani

Robert-Ferris

Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD.

“Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.”

The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator’s choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN.

The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act.

Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN.

OncLive: What were the updated findings from CheckMate-141 presented at ASCO?

Ferris: The data that were presented at the 2016 ASCO Annual Meeting were further evaluations and follow-up on some preliminary data—originally presented at the 2016 AACR Annual Meeting—that listed the OS results.

At ASCO, we recapped the primary endpoint of OS as an important endpoint for immunotherapies because response rate and progression-free survival may not be as accurate. Ultimately, the FDA and people at large want OS. In this study, OS was 36% at 1 year in the nivolumab-treated arm and 16.6% in the comparator arm, which was investigator’s choice of single-agent chemotherapy, consisting of methotrexate, docetaxel, or cetuximab. In this phase III randomized trial, nivolumab was given in a 2:1 randomization: 240 patients received nivolumab and 120 received investigator’s choice.

Also at ASCO, we presented further evaluations consisting of what the regimens are in the comparator arm. There was about 20% each of docetaxel and methotrexate and 12% of cetuximab. Approximately 60% of the patients had prior cetuximab exposure and we stratified by cetuximab as a prior therapy. We also demonstrated the ORR, which was 13.3% in the nivolumab-treated arm versus 5.8% in the investigator’s choice arm.

Therefore, there was an improvement in overall response, but the difference seemed more modest than the OS benefit—which was a doubling—with 20% more patients alive at 1 year. This reinforces the concept that perhaps response rate may not be the best endpoint. Progression-free survival (PFS) was double at 6 months, with about 20% in the nivolumab arm versus about 9.9% in the investigator’s choice arm. The median PFS was not different, but the 6-month PFS was twice as high. The time to response was about 2 months in each arm at the first assessment.

Your analysis also looked at biomarkers. Can you discuss these findings and their significance?

The p16 or HPV-positive group had a better hazard ratio for OS than the overall study population. The hazard ratio was .73 for the overall population, using a preplanned interim analysis. With the HPV-positive group, we had a hazard ratio of .55 and the HPV-negative group had a hazard ratio of .99. It is still favoring the nivolumab-treated patients but, with the curves separated earlier in the HPV-positive group, one could see the improvement with nivolumab at about 1 to 2 months. It took 7 or 8 months with the HPV-negative group to show a separation of the curves in favor of nivolumab.

We looked at PD-L1 levels, and PD-L1—using a 1% or above level—had an improvement in the PD-L1–positive patients in favor of nivolumab in terms of OS and ORR. When we looked at 5% and 10% thresholds of PD-L1, the OS did not seem to improve. Therefore, in all levels above 1%, the OS was similarly beneficial over the PD-L1 less-than-1% group. However, essentially all levels of PD-L1–positivity and PD-L1–negativity still favored nivolumab, but the benefit was more when its levels were greater than 1%.

We could combine HPV status with PD-L1 status and look at subsets; however, essentially every subset benefited, whether it was PD-L1–negative or positive. This indicates that, in this group of patients, who progress within 6 months of platinum-based therapy, that no current systemic therapeutic options benefit patients as well as nivolumab.

With regard to these findings, what are you most excited about?

Head and neck cancer is a difficult disease. Until recently, we didn’t know the impact of this enrichment for HPV-positive virus-induced subsets and we didn’t know if this was an immune responsive cancer. Clearly, it is. We have all of the hallmarks that we have seen for a bright future—based on the melanoma data—and a series of other cancers indicating response rates in the 15% to 20% range, suggesting that we now have a platform of the PD-1 pathway to combine with other checkpoints and to integrate earlier in disease with radiation and chemotherapy.

We have a demonstration of head and neck cancer as an immune-responsive cancer. We are beginning to get an idea of the biomarkers and starting to be able to segment patients who will benefit. Now, we have a large comparative trial with an OS endpoint and tissue to look at biomarkers to try and understand what the best future combinations will be.

What are some questions that you still hope to answer regarding nivolumab in head and neck cancer?

We have to get down deeper into the nonresponders. We should acknowledge that the majority of patients neither had a response nor benefited. Understanding who is more likely to benefit is useful, but we also need to understand the levels of alternative checkpoint receptors or other biomarkers of resistance.

We have sequential lymphocyte specimens from the peripheral blood, tissues, and serum so those are intensively under evaluation. There are interferon gamma signatures that have risen from the melanoma checkpoint field that will certainty be applied, as well.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

August, 2016|Oral Cancer News|

Merck Says FDA Accepts Its SBLA For Keytruda For Treatment Of Head & Neck Cancer

Source: www.finchannel.com
Author: Fin Channel News Editorial Staff
 
mercke1423056380602

The FINANCIAL — Merck, known as MSD outside the United States and Canada, on April 13 announced that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

The application is seeking approval for KEYTRUDA as a single agent at a dose of 200 mg administered intravenously every three weeks. The FDA granted Priority Review with a PDUFA, or target action, date of Aug. 9; the sBLA will be reviewed under the FDA’s Accelerated Approval program, according to Merck.

“Starting in the early days of our development program, we have explored the role of KEYTRUDA for patients with head and neck cancer, a difficult-to-treat and debilitating disease with very few treatment options,” said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “We are encouraged by the data emerging from our program in this type of cancer, and welcome today’s news as this is an important step toward making KEYTRUDA available to these patients.”

Merck currently has the largest immuno-oncology clinical development program in head and neck cancer and is advancing multiple registration-enabling studies with KEYTRUDA as a single agent and in combination with chemotherapy.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

April, 2016|Oral Cancer News|

Nivolumab Could Change Head and Neck Cancer Treatment Paradigm

Source: www.Targetedonc.com
Author: Laura Panjwani
 

“To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer.” – Robert Ferris, MD, PhD

With the phase III CheckMate-141 trial being stopped early due to the anti–PD-1 agent nivolumab having met its primary endpoint of overall survival improvement in head and neck cancer, Robert Ferris, MD, PhD, couldn’t be more elated.

“This is what I’ve devoted my career to, and it is gratifying to see that really come to pass,” said Ferris, professor and chief, Division of Head and Neck Surgery, vice chair for Clinical Operations, associate director for Translational Research, and coleader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute, in an exclusive interview with Targeted Oncology.

“To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer. There is now hope for a lot of patients and physicians who have been frustrated by this difficult-to-treat disease. This opens up a whole new class of therapies for this population.”

Ferris, who acted as cochair/coprimary investigator for the trial alongside Maura Gillison, MD, PhD, Ohio State University, said the trial pitted nivolumab against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel in patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).

Eligible patients who are still enrolled in the study are now able to continue their current treatment regimen, or switch over to nivolumab. Ferris says the prospect of having a new drug available for SCCHN is exciting, especially considering the last FDA approval for the disease type came in 2006.

“It was 2006 when cetuximab was approved and that was a relatively modest advance, although it was the first targeted therapy. We have a population without any other therapeutic options and a very rapid progression,” he said.

“Anti–PD-1 agents have had promising data in melanoma and squamous non–small cell lung cancer (NSCLC). Squamous NSCLC genomically resembles HPV-negative head and neck cancer in its behavior regarding carcinogen exposure. Therefore, we felt it might respond well to anti–PD-1 agents, too. We designed the study to hopefully create something new and effective for an essentially hopeless palliative group of patients.”

The phase III data have not yet been released from the trial, though early discontinuation has generated significant excitement in the field. The trial was scheduled to run until October 2016, has generated significant excitement in the field, says Ferris, who is a primary author on the abstract submitted for presentation at the ASCO Annual Meeting.

Ferris says the study was designed reflect the idea that there are different standards of care for SCCHN throughout the world, which is why cetuximab, methotrexate, or docetaxel were chosen for the control arms.

“We still don’t have public data for what all of the standard of care selections were, but we do know that cetuximab tends to be used more in North America. Meanwhile, the other 2 agents are more likely to be used in Europe and other countries because cetuximab is not approved there,” he said.

“The benefits are really very modest with those single-agent treatments and they are toxic. There is very much a need for a new treatment. We are very interested in the toxicity profile of nivolumab, as it has proven to be well tolerated in other cancers.”

Ferris adds that the excitement generated in the field stems from the revelation of efficacy for pembrolizumab (Keytruda) at the 2015 ASCO Annual Meeting, saying the data from both pembrolizumab and nivolumab “appear to be very similar.”

“There was a suspicion that nivolumab would be promising in head and neck cancer, as well. There is a great deal of buzz from medical oncology leaders all over the country regarding this. People have really been waiting with bated breath for something for our patients. This is a real win for the community and for a population of patients with a devastating disease in a very important area of the body,” he said.

“This disease can disrupt speaking, drinking, swallowing, and has catastrophic consequences. I expect enthusiasm and support from the community regarding this.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2016|Oral Cancer News|

NCI-designated Cancer Centers Urge HPV Vaccination for the Prevention of Cancer

Source: www.medicine.wustl.edu
Author: Washington University School of Medicine in St. Louis Staff
 

Approximately 79 million people in the United States are currently infected with a human papillomavirus (HPV) according to the Centers for Disease Control and Prevention (CDC), and 14 million new infections occur each year. Several types of high-risk HPV are responsible for the vast majority of
cervical, anal, oropharyngeal (middle throat) and other genital cancers. The CDC also reports that each year in the U.S., 27,000 men and women are diagnosed with an HPV-related cancer, which amounts to a new case every 20 minutes. Even though many of these HPV-related cancers are preventable with a safe and effective vaccine, HPV vaccination rates across the U.S. remain low.

Together we, a group of the National Cancer Institute (NCI)- designated Cancer Centers, recognize these low rates of HPV vaccination as a serious public health threat. HPV vaccination represents a rare opportunity to prevent many cases of cancer that is tragically underused. As national leaders in cancer research and clinical care, we are compelled to jointly issue this call to action.

According to a 2015 CDC report, only 40 percent of girls and 21 percent of boys in the U.S. are receiving the recommended three doses of the HPV vaccine. This falls far short of the goal of 80 percent by the end of this decade, set forth by the U.S. Department of Health and Human Service’s Healthy People 2020 mission. Furthermore, U.S. rates are significantly lower than those of countries such as Australia (75 percent), the United Kingdom (84-92 percent) and Rwanda (93 percent), which have shown that high vaccination rates are currently achievable. The HPV vaccines, like all vaccines used in the U.S., passed extensive safety testing before and after being approved by the U.S. Food and Drug Administration (FDA). The vaccines
have a safety profile similar to that of other vaccines approved for adolescents in the U.S. Internationally, the safety of HPV vaccines has been tested and approved by the World Health Organization’s Global Advisory Committee on Vaccine Safety. CDC recommends that boys and girls receive three doses of HPV vaccine at ages 11 or 12 years. The HPV vaccine series can be started in preteens as early as age 9 and should be completed before the 13th birthday. The HPV vaccine is more effective the earlier it is given; however, it is also recommended for young women until age 26 and young men until age 21.The low vaccination rates are alarming given our current ability to safely and effectively save lives by preventing HPV infection
and its associated cancers. Therefore, we urge parents and health care providers to protect the health of our children through a number of actions:

  • We encourage all parents and guardians to have their sons and daughters complete the 3-dose HPV vaccine series before the 13th birthday, and complete the series as soon as possible in children aged 13 to 17. Parents and guardians should talk to their health care provider to learn more about HPV vaccines and their benefits.
  • We encourage young men (up to age 21) and young women (up to age 26), who were not vaccinated as preteens or teens, to complete the 3-dose HPV vaccine series to protect themselves against HPV.
  • We encourage all health care providers to be advocates for cancer prevention by making strong recommendations for childhood HPV vaccination. We ask providers to join forces to educate parents/guardians and colleagues about the importance and benefits of HPV vaccination. HPV vaccination is our best defense in stopping HPV infection  in our youth and preventing HPV-related cancers in our communities. The HPV vaccine is CANCER PREVENTION. More information is available from the CDC.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

 

February, 2016|Oral Cancer News|

FDA Clears First Tobacco Product for Marketing

For the first time since it was given the power to regulate tobacco, the US Food and Drug Administration (FDA) has authorized marketing of a new product.

The agency said that eight new smokeless snus products, to be sold in the United States under the “General” brand name by Stockholm-based Swedish Match AB, are now authorized under the premarket tobacco application pathway, which was established by the 2009 Family Smoking Prevention and Tobacco Control Act. Snus cannot be marketed as “FDA-approved,” however.

“Today’s action demonstrates that the premarket tobacco application process is a viable pathway under which products can be marketed, as long as the public health can be protected,” said Mitch Zeller, director of the FDA’s Center for Tobacco Products, in a statement.

This is the first time any tobacco maker has completed the rigorous premarket tobacco application review process at the agency; others have had products approved by proving they are substantially equivalent to what is already on the market.

The agency said that Swedish Match provided evidence that “these products would likely provide less toxic options if current adult smokeless tobacco users used them exclusively.” The agency also agreed with the company that snus’ availability would not result in substantial new use, delay quit attempts, or attract ex-smokers.

Swedish Match had been seeking separately to remove warnings that snus is harmful, but the agency has not yet ruled on that request.

In that separate application, Swedish Match was seeking to have the 10 types of snus it already sells in the United States designated as modified-risk tobacco products. The agency accepted the company’s application in August 2014 and held a meeting of its advisory panel to review the evidence in April 2015.

The company wanted to remove warnings that snus could cause gum disease and tooth loss or mouth cancer. It also sought to label its products with the statement that reads, “No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.” The advisory committee could not reach consensus on whether snus was a safer alternative to smoking, and also was not convinced that the product would not attract new users. At that meeting, Dennis Henigan, director of legal and policy analysis for the Campaign for Tobacco-Free Kids, said Swedish Match had failed to show that users would not use both cigarettes and snus, or that young people would not initiate use.

Snus, which is ground tobacco, salt, and water, comes in a pouch that users place under their upper lip. It can be used for up to 30 minutes, according to the company. It is popular in Sweden, but less so in the United States. Swedish Match says its General brand accounts for 11% of American convenience store snus sales. The 60 million cans it sells annually in the United States are dwarfed by the billion cans of smokeless tobacco sold.

The Centers for Disease Control and Prevention estimates that less than 4% of adults use smokeless tobacco, with rates highest among men aged 18 to 25 years (10%). A 2014 Centers for Disease Control and Prevention survey of high school students found that 5.5% of overall used smokeless tobacco, and an additional 1.9% reported current use of snus.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2015|Oral Cancer News|

SA Developed Melanoma Drug Now Seen Effective in Fighting Lung Cancer

Source: www.woai.com
Author: News Radio 1200 WOAI Staff

 

1229_1264794779Keytruda, a cancer drug developed largely at San Antonio’s START Center, has already proven to be effective in treating advanced melanoma to the point that it is the major part of former President Jimmy Carter’s treatment.  Now, News Radio 1200 WOAI reports Keytruda has been given ‘fast track’ approval by the FDA for use in treating lung cancer, the leading cause of cancer deaths in the United States.

Dr. Amita Patnaik, a researcher and oncologist at START who helped develop the drug, says the impact of Keytruda on lung cancer patients has been amazing.

“Close to 40% of those patients will receive a response,” she said.  “And of those patients who receive a response, about 80% of those patients will have a long term response.”

The life saving potential of Keytruda in fighting non small cell lung tumors is obvious.  An estimated 221,000 Americans are diagnosed with lung cancer each year, and 158,000 die of the disease annually.

Dr. Patnaik says Keytruda is becoming the most successful of what are known as ‘targeted therapies,’ drugs which trigger the body to take action to fight the cancer.  She says both melanoma and lung cancer work essentially the same way to undermine the body’s defenses.

“The commonality between melanoma and lung cancer is there is a supressive effect of the cancer on the immune system.”

She says Keytruda essentially overrides that supressive effect, prompting the body to restart its natural immune defenses and fight the cancer.

That means the treatment takes place without chemotherapy.

“Thus avoiding some of the toxicities associated with chemotherapy including hair loss, fatigue, a drop in counts, nausea and vomiting, and the spectrum of negative side effects you get with chemo.”

Dr. Patnaik says several other types of cancers work the same way, ‘turning off’ the body’s natural immune systems, and she says there are indications that Keytruda will work for those cancers as well.

“Keytruda is showing activity in about ten or more other cancers, including liver cancer, head and neck cancer, and in a rare form of breast cancer.”

The FDA granted Keytruda ‘breakthrough therapy designation’ because of demonstrated preliminary clinical evidence that the drug may ‘offer a substantial improvement over available therapies.’

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

October, 2015|Oral Cancer News|

The Cost of Cancer Drugs

Source: www.cbsnew.com
Author: Lesley Stahl
 

The following is a script of “The Cost of Cancer Drugs” which aired on October 5, 2014, and was rebroadcast on June 21, 2015. Lesley Stahl is the correspondent. Richard Bonin, producer.

Cancer is so pervasive that it touches virtually every family in this country. More than one out of three Americans will be diagnosed with some form of it in their lifetime. And as anyone who’s been through it knows, the shock and anxiety of the diagnosis is followed by a second jolt: the high price of cancer drugs.

They are so astronomical that a growing number of patients can’t afford their co-pay, the percentage of their drug bill they have to pay out-of-pocket. As we first reported in October, this has led to a revolt against the drug companies led by some of the most prominent cancer doctors in the country.

Dr. Leonard Saltz: We’re in a situation where a cancer diagnosis is one of the leading causes of personal bankruptcy.

Dr. Leonard Saltz is chief of gastrointestinal oncology at Memorial Sloan Kettering, one of the nation’s premier cancer centers, and he’s a leading expert on colon cancer.

Lesley Stahl: So, are you saying in effect, that we have to start treating the cost of these drugs almost like a side effect from cancer?

Dr. Leonard Saltz: I think that’s a fair way of looking at it. We’re starting to see the term “financial toxicity” being used in the literature. Individual patients are going into bankruptcy trying to deal with these prices.

Lesley Stahl: The general price for a new drug is what?

Dr. Leonard Saltz: They’re priced at well over $100,000 a year.

Lesley Stahl: Wow.

Dr. Leonard Saltz: And remember that many of these drugs, most of them, don’t replace everything else. They get added to it. And if you figure one drug costs $120,000 and the next drug’s not going to cost less, you’re at a quarter-million dollars in drug costs just to get started.

Lesley Stahl: I mean, you’re dealing with people who are desperate.

Dr. Leonard Saltz: I do worry that people’s fear and anxiety are being taken advantage of. And yes, it costs money to develop these drugs, but I do think the price is too high.

The drug companies say it costs over a billion dollars to bring a new drug to market, so the prices reflect the cost of innovation.

The companies do provide financial assistance to some patients, but most people aren’t eligible. So many in the middle class struggle to meet the cost of their co-payments. Sometimes they take half-doses of the drug to save money. Or delay getting their prescriptions refilled.

Dr. Saltz’s battle against the cost of cancer drugs started in 2012 when the FDA approved Zaltrap for treating advanced colon cancer. Saltz compared the clinical trial results of Zaltrap to those of another drug already on the market, Avastin. He says both target the same patient population, work essentially in the same way. And, when given as part of chemotherapy, deliver the identical result: extending median survival by 1.4 months, or 42 days.

Dr. Leonard Saltz: They looked to be about the same. To me, it looked like a Coke and Pepsi sort of thing.

Then Saltz, as head of the hospital’s pharmacy committee, discovered how much it would cost: roughly $11,000 per month, more than twice that of Avastin.

Lesley Stahl: So $5,000 versus $11,000. That’s quite a jump. Did it have fewer side effects? Was it less toxic? Did it have…

Dr. Leonard Saltz: No…

Lesley Stahl: …Something that would have explained this double price?

Dr. Leonard Saltz: If anything, it looked like there might be a little more toxicity in the Zaltrap study.

He contacted Dr. Peter Bach, Sloan Kettering’s in-house expert on cancer drug prices.

Lesley Stahl: So Zaltrap. One day your phone rings and it’s Dr. Saltz. Do you remember what he said?

Dr. Peter Bach: He said, “Peter, I think we’re not going to include a new cancer drug because it costs too much.”

Lesley Stahl: Had you ever heard a line like that before?

Dr. Peter Bach: No. My response was, “I’ll be right down.”

Lesley Stahl: You ran down.

Dr. Peter Bach: I think I took the elevator. But yes, exactly.

Bach determined that since patients would have to take Zaltrap for several months, the price tag for 42 days of extra life would run to nearly $60,000. What they then decided to do was unprecedented: reject a drug just because of its price.

Dr. Peter Bach: We did it for one reason. Because we need to take into account the financial consequences of the decisions that we make for our patients. Patients in Medicare would pay more than $2,000 a month themselves, out-of-pocket, for Zaltrap. And that that was the same as the typical income every month for a patient in Medicare.

Lesley Stahl: The co-pay.

Dr. Peter Bach: Right. 20 percent. Taking money from their children’s inheritance, from the money they’ve saved. We couldn’t in good conscience say, “We’re going to prescribe this more expensive drug.”

And then they trumpeted their decision in the New York Times. Blasting what they called “runaway cancer drug prices,” it was a shot across the bow of the pharmaceutical industry and Congress for passing laws that Bach says allow the drug companies to charge whatever they want for cancer medications.

Dr. Peter Bach: Medicare has to pay exactly what the drug company charges. Whatever that number is.

Lesley Stahl: Wait a minute, this is a law?

Dr. Peter Bach: Yes.

Lesley Stahl: And there’s no negotiating whatsoever with Medicare?

Dr. Peter Bach: No.

Another reason drug prices are so expensive is that according to an independent study, the single biggest source of income for private practice oncologists is the commission they make from cancer drugs. They’re the ones who buy them wholesale from the pharmaceutical companies, and sell them retail to their patients. The mark-up for Medicare patients is guaranteed by law: the average in the case of Zaltrap was six percent.

Dr. Leonard Saltz: What that does is create a very substantial incentive to use a more expensive drug, because if you’re getting six percent of $10, that’s nothing. If you’re getting six percent of $10,000 that starts to add up. So now you have a real conflict of interest.

But it all starts with the drug companies setting the price.

Dr. Peter Bach: We have a pricing system for drugs which is completely dictated by the people who are making the drugs.

Lesley Stahl: How do you think they’re deciding the price?

Dr. Peter Bach: It’s corporate chutzpah.

Lesley Stahl: We’ll just raise the price, period.

Dr. Peter Bach: Just a question of how brave they are and how little they want to end up in the New York Times or on 60 Minutes.

That’s because media exposure, he says, works. Right after their editorial was published, the drug’s manufacturer, Sanofi, cut the price of Zaltrap by more than half.

Dr. Peter Bach: It was a shocking event. Because it was irrefutable evidence that the price was a fiction. All of those arguments that we’ve heard for decades, “We have to charge the price we charge. We have to recoup our money. We’re good for society. Trust us. We’ll set the right price.” One op-ed in the New York Times from one hospital and they said, “Oh, okay, we’ll charge a different price.” It was like we were in a Turkish bazaar.

Lesley Stahl: What do you mean?

Dr. Peter Bach: They said, “This carpet is $500” and you say, “I’ll give you $100.” And the guy says, “Okay.” They set it up to make it highly profitable for doctors to go for Zaltrap instead of Avastin. It was crazy!

But he says it got even crazier when Sanofi explained the way they were changing the price.

Dr. Peter Bach: They lowered it in a way that doctors could get the drug for less. But patients were still paying as if it was high-priced.

Lesley Stahl: Oh, come on.

Dr. Peter Bach: They said to the doctor, “Buy Zaltrap from us for $11,000 and we’ll send you a check for $6,000.” Then you give it to your patient and you get to bill the patient’s insurance company as if it cost $11,000. So it made it extremely profitable for the doctors. They could basically double their money if they use Zaltrap.

“High cancer drug prices are harming patients because either you come up with the money, or you die.”

All this is accepted industry practice. After about six months, once Medicare and private insurers became aware of the doctor’s discount, the price was cut in half for everyone.

John Castellani: The drug companies have to put a price on a medicine that reflects the cost of developing them, which is very expensive and takes a long period of time, and the value that it can provide.

John Castellani is president and CEO of PhRMA, the drug industry’s trade and lobbying group in Washington.

Lesley Stahl: If you are taking a drug that’s no better than another drug already on the market and charging twice as much, and everybody thought the original drug was too much…

John Castellani: We don’t set the prices on what the patient pays. What a patient pays is determined by his or her insurance.

Lesley Stahl: Are you saying that the pharmaceutical company’s not to blame for how much the patient is paying? You’re saying it’s the insurance company?

John Castellani: I’m saying the insurance model makes the medicine seem artificially expensive for the patient.

He’s talking about the high co-pay for cancer drugs. If you’re on Medicare, you pay 20 percent.

Lesley Stahl: Twenty percent of $11,000 a month is a heck of a lot more than 20 percent of $5,000 a month.

John Castellani: But why should it be 20 percent instead of five percent?

Lesley Stahl: Why should it be $11,000 a month?

John Castellani: Because the cost of developing these therapies is so expensive.

Lesley Stahl: Then why did Sanofi cut it in half when they got some bad publicity?

John Castellani: I can’t respond to a specific company.

Sanofi declined our request for an interview, but said in this email that they lowered the price of Zaltrap after listening “to early feedback from the oncology community and … To ensure affordable choices for patients…”

Dr. Hagop Kantarjian: High cancer drug prices are harming patients because either you come up with the money, or you die.

Hagop Kantarjian chairs the department of leukemia at MD Anderson in Houston. Inspired by the doctors at Sloan Kettering, he enlisted 119 of the world’s leading leukemia specialists to co-sign this article about the high price of drugs that don’t just add a few weeks of life, but actually add years, like Gleevec.

It treats CML, one of the most common types of blood cancer that used to be a death sentence, but with Gleevec most patients survive for 10 years or more.

Dr. Hagop Kantarjian: This is probably the best drug we ever developed in cancer.

Lesley Stahl: In all cancers?

Dr. Hagop Kantarjian: So far. And that shows the dilemma, because here you have a drug that makes people live their normal life. But in order to live normally, they are enslaved by the cost of the drug. They have to pay every year.

Lesley Stahl: You have to stay on it. You have to keep taking it.

Dr. Hagop Kantarjian: You have to stay on it indefinitely.

Gleevec is the top selling drug for industry giant Novartis, bringing in more than $4 billion a year in sales. $35 billion since the drug came to market. There are now several other drugs like it. So, you’d think with the competition, the price of Gleevec would have come down.

Dr. Hagop Kantarjian: And yet, the price of the drug tripled from $28,000 a year in 2001 to $92,000 a year in 2012.

Lesley Stahl: Are you saying that the drug companies are raising the prices on their older drugs.

Dr. Hagop Kantarjian: That’s correct.

Lesley Stahl: Not just the new ones. So you have a new drug that might come out at a $100,000, but they are also saying the old drugs have to come up to that price, too?

Dr. Hagop Kantarjian: Exactly. They are making prices unreasonable, unsustainable and, in my opinion, immoral.

When we asked Novartis why they tripled the price of Gleevec, they told us, “Gleevec has been a life-changing medicine … When setting the prices of our medicines we consider … the benefits they bring to patients … The price of existing treatments and the investments needed to continue to innovate…”

[Dr. Hagop Kantarjian: This is quite an expensive medication.]

Dr. Kantarjian says one thing that has to change is the law that prevents Medicare from negotiating for lower prices.

Dr. Hagop Kantarjian: This is unique to the United States. If you look anywhere in the world, there are negotiations. Either by the government or by different regulatory bodies to regulate the price of the drug. And this is why the prices are 50 percent to 80 percent lower anywhere in the world compared to the United States.

Lesley Stahl: Fifty percent to 80 percent?

Dr. Hagop Kantarjian: Fifty percent to 80 percent.

Lesley Stahl: The same drug?

Dr. Hagop Kantarjian: Same drug. American patients end up paying two to three times more for the same drug compared to Canadians or Europeans or Australians and others.

Lesley Stahl: Now, Novartis, which makes Gleevec, says that the price is fair because this is a miracle drug. It really works.

Dr. Hagop Kantarjian: The only drug that works is a drug that a patient can afford.

The challenge, Dr. Saltz at Sloan Kettering says, is knowing where to draw the line between how long a drug extends life and how much it costs.

Lesley Stahl: Where is that line?

Dr. Leonard Saltz: I don’t know where that line is, but we as a society have been unwilling to discuss this topic and, as a result, the only people that are setting the line are the people that are selling the drugs.

Since we first broadcast our story, President Obama asked Congress to change the law and allow Medicare to negotiate prices with drug manufacturers. Few believe, however, that Congress will let that happen anytime soon.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

 

FDA Advisory Committee hesitates to endorse message of safe smokeless tobacco

Source: www.medpagetoday.com
Author: Shannon Firth

An FDA advisory panel were reluctant to recommend a gentler warning label for one brand of smokeless tobacco products at a committee hearing on Friday.

snus

Swedish Match North America (SMNA), the first company to be considered for a modified risk tobacco designation by the FDA, is asking to replace a current label warning, “This product is not a safe alternative to cigarettes,” with this: “Warning: No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.”

It also wants to drop warnings required for other smokeless tobacco products about oral cancers, tooth loss, and gum disease.

In a key vote, the eight-member FDA’s Tobacco Products Scientific Advisory Committee split 4-4 on whether the claim that snus offer a “substantially lower risk” claim relative to cigarettes is justified.

Many members said the health risks were lower for certain tobacco-related illnesses, but not for all health concerns. Those who disputed the claim argued that it could not be taken as a “global statement” — as there are known risks to pregnant women and uncertain risks for adolescents.

As for the proposed label change, the whole committee agreed that the sponsor’s statements would not suffice. Gary Giovino, PhD, chair of the department of Community Health and Health Behavior at the State University of New York at Buffalo, felt the statement was “dismissive of the health risks.” The word “but” in any sentence seems to negate the first half, he said.

Snus is a finely ground smokeless tobacco powder in a filter packet that is placed under the upper lip.

In his opening remarks on Thursday, Mitch Zeller, JD, director of the FDA’s Center for Tobacco Products, said that in the past companies alone decided how to advertise their products — a practice which proved damaging to consumers’ health. “Now it’s the FDA who serves as the regulatory gatekeeper, standing between consumers and the companies seeking to make claims about their products.”

To meet the standards of a modified risk tobacco product, Zeller explained, “Applicants must not only demonstrate that the products, as actually used by consumers, will significantly reduce risks to individual users of those products; they must demonstrate that they will benefit the population as a whole – taking into account both users and non-users of tobacco products.”

In its application, Swedish Match has asked to revise the labels for 10 snus products. It would maintain its warning that smokeless tobacco is addictive.

Oral Safety Unproven
The committee was unmoved by the firm’s evidence related to gum disease and tooth loss and voted 8-0 against supporting a conclusion that snus products “do not pose a risk of gum diseases or tooth loss.”

Or as Thomas Novotny, MD, MPH, the graduate school of public health at the University of California San Diego State said, when explaining his vote, “It’s not causal relationships that we’re after, it’s perception of risk and the studies don’t rule that out.”

The committee’s vote was likely influenced by Scott Tomar, DMD, MPH, DrPH, of the department of Community Dentistry and Behavioral Science, at the University of Florida, who said that “advanced gingival recession can result in tooth loss.” One of the studies presented showed a relationship between gingival recession and snus use.

As to whether snus products also “do not pose risks of oral cancer” to consumers, the committee was split 3-3 with two abstentions.
“I think the data are tending towards no increased risk but I’m not quite ready to go there,” said Giovino, one of the abstainers.

Pebbles Fagan, PhD, MPH, associate professor and member of the Cancer Prevention and Control Program at the University of Hawaii, said that based on the absence of women in the larger cohort studies, she was not comfortable claiming that snus products posed no risk of oral cancer.

Can the ‘Swedish Experience’ Cross the Ocean?
Perhaps the most important questions the committee voted on was whether the proposed labeling change would help or harm consumers. Swedish Match threw the weight of its argument behind the “Swedish Experience,” a series of government, academic ,and industry studies showing a dramatic shift from cigarette smoking to snus in the mid-1990s. The firm argued that Swedish men reduced their risk of tobacco-related diseases.

But asked whether American tobacco users would likely follow suit — swapping cigarettes for snus — panel members were unconvinced.

Only one committee member said such a switch was likely, against six voting against and one abstention.

Richard O’Connor, PhD, associate professor of oncology at the Roswell Park Cancer Institute, in Buffalo New York, the lone panelist to agree that the experience in Sweden might translate to the U.S., said the data informed “a potential pattern in the U.S.”

Another subpopulation of obvious concern is adolescents. Timothy McAfee, PhD, MPH, director of the Office on Smoking and Health at the CDC, cited animals studies on tobacco addiction that showed “deleterious effects on adolescent brain development.”

On the plus side for Swedish Match, the majority of the committee felt it unlikely that nonusers of tobacco would pick up the snus habit, although three committee members abstained from this question because they did not believe there was enough data to support such a scenario.

Lars-Erik Rutqvist, the senior vice president of scientific affairs at Swedish Match said the company was pleased with the discussion at the hearing. “On the whole they seemed to accept the fact that there is a considerable risk reduction in our products and of course that’s very important. It’s part of the definition of a modified risk product.” Rutqvist added that he would expect to continue discussions with the FDA while awaiting their decision this summer.

“I look forward to the path forward for us.”

The FDA is not required to follow the advice of its advisory committee but it usually does.

April, 2015|Oral Cancer News|