Cancer Deaths Rates Drop Overall, but Not All Types

Death rates from cancer continue to drop in the U.S., but within this overall picture there are winners and losers, with mortality from certain types of cancer on the rise and certain populations remaining at increased risk of dying from malignancies.

From 1999 to 2015, cancer mortality decreased each year by 1.4% in women and 1.8% in men; and in children, the yearly rate decreased 1.5% from 2011 to 2015, according to the annual report on cancer in the U.S. from the National Cancer Institute (NCI) and others.

“This year’s report is an encouraging indicator of progress we’re making in cancer research,” said NCI Director Ned Sharpless, MD, in a statement. “As overall death rates continue to decline for all major racial and ethnic groups in the United States, it’s clear that interventions are having an impact.”

In both men and women, the rates of cancer mortality decreased from 2011 to 2015 for those with lung, colorectal, esophageal, kidney, and gastric cancers, and leukemia, melanoma, and non-Hodgkin’s lymphoma (NHL).

In men alone, cancer mortality also decreased for laryngeal cancer, multiple myeloma and prostate cancer (though it leveled off from 2013 to 2015, see more below). In women only, cancer mortality also decreased for breast, ovarian, cervical, gallbladder, bladder, and oral cavity and pharyngeal cancers.

“The overall reduction in cancer mortality has been dramatic,” said Stephen Edge, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, who was not involved with the report. “This welcome news can be attributed to a combination of screening and improved treatment, and is likely to decrease further with broad application of new therapies, including immunotherapy.”

The report is a collaboration by the NCI, CDC, American Cancer Society, and North American Association of Central Cancer Registries (NAACCR).

Published in Cancer, the report also highlights areas where more work is needed, said Sharpless.

With 5-year death rate trends during this period described by average annual percent change (AAPC), a number of common cancers in men increased from 2011 to 2015:

• Non-melanoma skin cancer (AAPC 2.8%)
• Liver cancer (1.6%)
• Oral cavity and pharyngeal cancer (1.0%)
• Soft-tissue sarcoma (0.8%)
• Brain and central nervous system (CNS) tumors (0.5%)
• Pancreatic cancer (0.2%)

And in women, increased death rates were seen in the following:

• Liver cancer (AAPC 2.7%)
• Uterine cancer (1.9%)
• Brain and CNS tumors (0.5%)
• Pancreatic cancer (0.2%)

“The fact that death rates from several cancers are still on the rise means we need to keep working to find strategies to encourage prevention and continue to make improvements in screening and treatment,” said NAACCR Executive Director Betsy A. Kohler, MPH, in a statement.

And while mortality from cancer continues to decrease overall, “concerning disparities persist relating to people’s social and ethnic background,” said Edge.

Black men (239.9 per 100,000) and black women (159.0 per 100,000) had the highest rates of cancer mortality, according to the report. Black men also had the highest rates of cancer incidence (558.2 per 100,000), but among women, whites had the highest cancer rates (428.7 per 100,000).

From 2008 to 2014, the incidence rates of cancer in the U.S. dropped by an average of 2.2% each year in men, while no decrease was observed in women. Overall, men had a higher incidence of cancer than women (502.0 versus 420.6 per 100,000). In children, rates of cancer incidence increased by 0.8% each year from 2010 to 2014.

Prostate Cancer Trends

In a study that accompanied the annual report, researchers looked closer at prostate cancer trends, revealing that from 2013 to 2015, mortality from the disease stopped falling after two decades of decline.

And from 2010 to 2014, the incidence of distant-stage disease increased from 7.8 to 9.2 cases per 100,000 men, reported Serban Negoita, MD, DrPH, of the NCI’s Surveillance Research Program, and colleagues.

“We’ve seen a concerning increase in the rates of men with advanced prostate cancer, a trend that could be related to changes in the use of prostate cancer screening,” said Edge.

Notably, new cases of prostate cancer in the U.S. dropped from 163 per 100,000 in 2007 to 104 cases per 100,000 in 2014 (average decrease of 6.5% per year) — raising questions about whether it’s a consequence of the U.S. Preventive Services Task Force’s (USPSTF) 2012 guidelines recommending against prostate-specific antigen (PSA) screening for asymptomatic men.

“The increase in late-stage disease and the flattening of the mortality trend occurred contemporaneously with the observed decrease in PSA screening in the population,” said Negoita in a statement. “Although suggestive, this observation does not demonstrate that one caused the other.”

However, the report found no increase in Gleason 9-10 disease, suggesting the increase in distant-stage disease could in part be due to better initial work-up of patients. “There are many factors that contribute to incidence and mortality, such as improvements in staging and treating cancer,” Negoita said.

Bobby Liaw, MD, of the Icahn School of Medicine at Mount Sinai, who was not involved with the study, said that with the recent change in USPSTF recommendations, there might eventually be a course correction, where again prostate cancers are caught at an earlier stage.

“The pendulum is coming back,” Liaw told MedPage Today. “We went from screening everyone to screening no one, now we’re coming back to a more middle ground.”

The USPSTF recently recommended that PSA screening for men ages 55 to 69 be an individual decision, but data reflecting this change might not be seen for a number of years.

Liaw highlighted that the plateauing of the survival — even with a slightly higher number of newly diagnosed advanced prostate cancer cases — speaks to the effectiveness of newer therapies in prostate cancer. “I actually take that as a promising sign that we’re still able to keep things steady,” he said.

The study was funded by the NCI, CDC, American Cancer Society, and NAACCR.

LAST UPDATED 05.23.2018

• Primary Source

  Cancer

  Source Reference: Cronin KA, et al “Annual report to the nation on the status of cancer, part I: National cancer statistics” Cancer 2018; doi:10.1002/cncr.31551.

• Secondary Source

  Cancer

  Source Reference: Negoita S, et al “Annual report to the nation on the status of cancer, part II: Recent changes in prostate cancer trends and disease characteristics” Cancer 2018; doi:10.1002/cncr.31549.

https://bit.ly/2IFXxKb

For Smoking Cessation, Money Whispers Louder than Nicotine Replacement

In a large, workplace-based randomized trial, smokers offered up to $600 to remain tobacco-free for 6 months were significantly more successful than those given free access to conventional cessation aids or to e-cigarettes.

But in absolute terms, the efforts were all wildly unsuccessful, with 6-month abstinence rates not even reaching 3% with the top-performing inducements, researchers reported in the New England Journal of Medicine.

“This trial showed that among unselected smokers, workplace smoking-cessation programs yielded low rates of smoking abstinence,” acknowledged Scott Halpern, MD, PhD, of the University of Pennsylvania in Philadelphia, and colleagues.

Moreover, “offering free cessation aids or free e-cigarettes did not increase abstinence among smokers who were given access to information and motivational text messages.”

The best rates were among participants offered both free cessation aids and a monetary reward of up to $600 at the 6-month benchmark.

But advocates of e-cigarettes for smoking cessation may take comfort in the study’s finding that sustained quit rates among those assigned to receive free NJOY vaping devices were twice as great as among participants offered a variety of free cessation aids (1.0% vs 0.5%) which could include e-cigarettes as well as conventional medications and nicotine replacement products.

The study involved employees at 54 companies, where a total of 6,131 were identified as smokers and were invited to participate in the trial through an opt-out procedure. After 125 proactively declined, the remaining 6,006 were randomized to be offered one of five interventions:

• “Usual care” consisting of information and motivational text messages (n=813)
• Free NJOY e-cigarettes in multiple flavors with no free access to other cessation aids (n=1,199)
• Free cessation aids including any approved nicotine replacement product or medication such as varenicline (Chantix) or bupropion (Zyban), as well as e-cigarettes (n=1,588)
• $600 paid in increments through the study period, based on remaining abstinent, plus free cessation aids (n=1,198)
• $600 deposit account redeemable at 6 months, but reduced in increments for failing to meet interim milestones, plus free cessation aids (n=1,208)

Participants could accept the intervention or not at their discretion. They were asked to report whether they were abstinent at months 1, 3, and 6, and also provided urine samples at these time points for cotinine testing as confirmation. Alternative tests were employed for participants using nicotine replacement therapies or e-cigarettes. If participants reported continued smoking or the testing indicated non-abstinence, the financial incentives were docked accordingly.

Because participants had not volunteered on their own initiative to stop smoking, Halpern and colleagues did not expect large numbers of cessation attempts or successes. As part of the study, participants were invited to access a website with smoking-cessation information that was also the portal through which they could order cessation aids or e-cigarettes. The researchers used participants’ history of website visits to gauge “engagement” with the program — that is, a demonstrated effort to quit smoking. Overall, only about 20% visited the website, with little variation among intervention groups.

Confirmed abstinence rates at 6 months among all those assigned to the interventions were as follows:

• Usual care: 0.1%
• Free cessation aids: 0.5%
• Free e-cigarettes: 1.0%
• $600 rewards paid during the study: 2.0%
• $600 deposit account redeemable after the study: 2.9%

But among the 1,191 who used the website and thus were considered engaged, “sustained abstinence rates were four to six times as high as those among participants who did not actively engage,” Halpern and colleagues wrote. In this group, 6-month abstinence rates ranged from 0.7% with usual care to 12.7% for the redeemable $600 deposit.

When the researchers looked for statistically significant differences among the interventions in the engaged subgroups, they found three:

• Redeemable deposit was superior to free cessation aids (OR 4.85, 95% CI 2.21-10.67)
• Redeemable deposit was superior to free e-cigarettes (OR 2.93, 95% CI 1.49-5.79)
• Reward was superior to free cessation aids (OR 3.47, 95% CI 1.53-7.87)

Although abstinence among those assigned to free e-cigarettes was numerically higher than for those assigned to a variety of cessation aids, both in the intention-to-treat population and the engaged subgroups, the differences did not come close to statistical significance when adjustments were made for the multiple comparisons.

Among the study limitations listed by Halpern and colleagues was the lack of a group receiving free conventional cessation aids only, without access to e-cigarettes. Nor was the combination of financial incentives plus e-cigarettes tested. But the researchers found that only one-third of engaged participants who could use a variety of cessation aids ever ordered e-cigarettes, versus 55% of the engaged subgroup assigned to free e-cigarettes. This, they argued, “supports the conclusion that offering free-e-cigarettes does not promote smoking cessation.”

The study was funded by the Vitality Institute.

Two co-authors reported relationships with VAL Health (behavioral economics consultant), CVS Health, Humana, Merck, Weight Watchers, Oscar Health Insurance, and Hawaii Medical Services Association. Halpern and other authors declared they had no relevant financial interests.

• Reviewed by F. Perry Wilson, MD, MSCEAssistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

• Primary Source

  New England Journal of Medicine

  Source Reference: Halpern S, et al “A pragmatic trial of e-cigarettes, incentives, and drugs for smoking cessation” N Engl J Med 2018; DOI: 10.1056/NEJMsa1715757.

https://bit.ly/2Lr7p8w

FDA Warns on OTC Teething Products with Benzocaine

Benzocaine-containing products sold over the counter to relieve babies’ teething pain are too risky and should no longer be sold, the FDA said Wednesday.

The agency “is asking companies to stop selling these products for such use,” according to a statement posted on the FDA website. “If companies do not comply, the FDA will initiate a regulatory action to remove these products from the market.”

New warnings will be added to other benzocaine-containing products for oral use, the agency said.

The specific problem cited Wednesday is methemoglobinemia, a condition that reduces the blood’s oxygen-carrying capacity, potentially to life-threatening levels. More than 400 cases have been reported to the FDA or appear in the medical literature, the agency said in a data summary. Among them were 11 incidents involving children younger than 2; one of which was fatal.

Out of 119 cases reviewed in detail, mostly involving adults (with the benzocaine-containing product most commonly used during transesophageal echocardiography), 36 reported methemoglobinemia levels of 30% to 55% — a normal level ranges from 1% to 2%. And in another 17 cases the level surpassed 55%, which is considered life-threatening. Four cases in total ended in death.

For parents looking to relieve teething pain in their infants, the FDA referred to recommendations from the American Academy of Pediatrics. These call for use of rubber teething rings or a simple finger-massage of the child’s gums. Medications are usually ineffective “because they wash out of the baby’s mouth within minutes,” the agency said.

In January 2017, the FDA warned against homeopathic teething tablets after finding “inconsistent amounts of belladonna” that sometimes far exceeded the amounts indicated on the label.

https://bit.ly/2s3PvAN

Teva says migraine drug could gain approval by mid-September

• The Food and Drug Administration should make an approval decision on Teva Pharmaceutical’s highly anticipated migraine treatment by Sept. 16, the company announced Wednesday.
• Fremanezumab is a monoclonal antibody that inhibits calcitonin gene-related peptides (CGRPs). Research has shown CGRPs affect vasodilation and sensory nervous system responses, which in turn have made them a prominent target for developers of headache and migraine medicines.
• Teva expected a June 16 target action date for the drug after U.S. regulators accepted its Biologics Licensing Application in December. But manufacturing issues at South Korea-based Celltrion, the sole supplier for fremanezumab’s active pharmaceutical ingredient, have caused some delays.

Teva needs fremanezumab. Over the past few years, the Israeli generics giant has run into serious challenges, most significantly pricing pressures in the U.S. generics market and patent expirations for its biggest brand, MS drug Copaxone (glatiramer acetate) — which accounted for around 17% of revenues in 2017.

The effects of those headwinds are becoming more pronounced too. Teva reported $5.1 billion in revenue for the first quarter, down 10% from the same period in 2017. In the states, revenue from Copaxone and generics decreased 40% and 23%, respectively, year-over-year.

Fremanezumab could offer a reprieve, given analysts expect big things out of the burgeoning CGRP class. Clarivate Analytics, for instance, named Amgen and Novartis’ recently approved CGRP inhibitor Aimovig (erenumab) as one of its top 12 drugs to watch in 2018. The firm expects Aimovig to fetch $1.17 billion in sales by 2022.

That positive outlook also underscores the competitive hurdles facing Teva’s drug. Not only is there Amgen and Novartis to contend with, but Eli Lilly and Alder Biopharmaceuticals also have CGRP inhibitors in late-stage testing for preventative treatment of migraine. And with the recent manufacturing delays, Lilly’s offering could make it to market before fremanezumab.

Investment bank Cowen & Co. pointed out as well that Aimovig, fremanezumab and Lilly’s galcanezumab have similar efficacy and safety profiles, meaning things like payer preference and modes of administration will be paramount in securing market share.

“It is in this arena that Teva’s fremanazumab may be at a disadvantage,” Cowen wrote in a March report. “Both Aimovig and galcanezumab will be supplied in an auto-injector that can be shipped to the patient and self-administered at home.”

“Fremanezumab appears to have a more viscous formulation and, while Teva has plans to develop an autoinjector, the first iteration of the product will be supplied in a pre-filled syringe that will most likely be administered by a healthcare provider. The inconvenience of leaving the home for a quarterly injection would likely put fremanezumab at a disadvantage.”

Getting fremanezumab onto the market ahead of rivals is therefore even more important for Teva. The new target action date suggests that may still be possible — or, at the very least, that Celltrion is quickly addressing regulatory concerns.

“We do not have any backup source that we have filed with the FDA. So, we are basically assuming and expecting that Celltrion will get in good shape in terms of GMP compliance, and we have no reasons to believe otherwise,” Teva CEO Kåre Schultz said during the company’s first quarter earnings call in early May.

Notably, the delays offset Teva’s use of a Priority Review Voucher, which it paid $150 million to acquire last year.

https://bit.ly/2Lp7VUD

Alkermes to present data on depression, schizophrenia portfolios at psych confab

Alkermes announced that new clinical data will be presented at the American Society of Clinical Psychopharmacology Annual Meeting in Miami, May 29 – June 1, 2018. The poster presentations will highlight data from the company’s depression and schizophrenia portfolios, including ALKS 5461, ARISTADA and ALKS 3831. Clinical data for ALKS 5461 will be presented, including long-term safety, tolerability and durability of antidepressant effect over a 52-week treatment period in patients with major depressive disorder. In addition, data from a human abuse potential study conducted in healthy, nondependent opioid users will be presented. In the study, ALKS 5461, a combination of buprenorphine with the mu-opioid receptor antagonist samidorphan, posed a low risk of abuse. Alkermes will present data related to ARISTADA, including results from a two-year safety study in patients with schizophrenia, and results from a pharmacokinetic and safety study evaluating Aripiprazole Lauroxil NanoCrystal Dispersion, a novel, investigational product designed for initiation onto ARISTADA. The company will also present results from a phase 2 study of ALKS 3831 in patients with schizophrenia and co-occurring alcohol use disorder

https://bit.ly/2GJteg6

Vanda started at buy by Citi

Citi starts Vanda with Buy rating, $26 price target. Citi analyst Joel Beatty initiated Vanda Pharmaceuticals with a Buy rating and $26 price target. The company’s 2018 sales are on track to be $180M-$200M, which largely supports the current enterprise value of $610M, Beatty tells investors in a research note. He believes upside in 2018 could come from sales growth plus a label expansion for Hetlioz, and Phase 2 tradipitant data. Further, late-stage pipeline agent tradipitant offers ” nearly a free call option,” the analyst contend

https://bit.ly/2xah2p6

Walgreen target cut by Leerink

Walgreens Boots Alliance price target lowered to $70 from $75 at Leerink. Leerink analyst David Larsen lowered his price target for Walgreens Boots Alliance to $70 from $75 as healthcare hub strategy is taking time and headwinds continue. The analyst reiterates a Market Perform rating on the shares.

https://bit.ly/2Lpbeep