Colorecal cancer commonly misdiagnosed in patients under 50

A recent survey has found that a significant number of patients who develop colorectal cancer (CRC) before the age of 50 are misdiagnosed several times. Multiple misdiagnoses often results in the disease being diagnosed at an advanced stage, decreasing survival rates.

Despite deaths from colorectal cancer cases falling significantly in the past decade, the disease remains the second leading cause of cancer-related deaths in the US. This may be due to a sharp increase of colorectal cancer diagnoses in young adults aged 20 to 49 years old.

Dr. Ronit Yarden, PhD, MHSA, the study’s lead author and director of medical affairs at the non-profit Colorectal Cancer Alliance, described this increase as “alarming”, stating:

Despite declining incidence in older adults, there has been a rapid and alarming rise in colorectal cancer incidence among young adults in recent decades. We do not yet know the cause of the rising incidence in younger patients, and there is little awareness of this trend among health care providers.”

Dr. Ronit Yarden, Lead Author

The study comprised 1,195 participants, 57% of which were diagnosed between ages 40-49, 33% diagnosed between 30-39, and 10 percent diagnosed before the age of 30.

Of these participants, 30 percent reported a family history of colorectal cancer, and eight percent had received a previous diagnosis of Lynch syndrome, which is a genetic condition associated with an increased risk of developing a number of different cancers, including CRC.

The survey, which was carried out over social media and funded by the Colorectal Cancer Alliance, aimed to “track the self-reported clinical psychosocial, financial and quality of life experiences of this often overlooked, group.”

It found that, while most patients over the age of 50 were diagnosed with CRC in its early stages, “most of the young-onset patients and survivors (71%) were diagnosed at advanced stages.”

Being diagnosed at stages III and IV meant the patients were forced to undergo aggressive therapies, resulting in a consequent decrease in their quality of life. Patients experienced neuropathy, anxiety, clinical depression, and sexual dysfunctions.

Why are younger people overlooked in colorectal cancer diagnoses?

Yarden hypothesizes that young people with colorectal cancer are often misdiagnosed as they “tend to be healthy.” She added, “Physicians may attribute patients’ symptoms to more common conditions, like hemorrhoids or inflammatory bowel syndrome, and may lack the urgency to refer patients to tests that may identify early-stage colorectal cancer.”

Yarden also acknowledges that there is a lack of awareness around colorectal cancer in younger people, and advises:

Young people need to be aware that colorectal cancer can happen at any age and it is not a disease of old people. Everybody should listen to their body and, if it doesn’t feel right, go to the doctor to be tested.”

She also emphasized the importance of recognizing the symptoms of the disease.

Symptoms of colorectal cancer include a change in bowel habits, including constipation, alternating bouts of constipation and diarrhea, and blood or mucus in the stool. Abdominal pain, a feeling that the bowels are never completely empty, and a constant need to go to the toilet can also be experienced.

Populations at a higher risk of developing CRC include African Americans, Alaska Natives and those with a family or personal history of colon or rectal polyps.

Although not involved in the research, Dr. Paul Oberstein, a medical oncologist and Medical Director at NYU Langone’s Perlmutter Cancer Center in New York spoke on the incidence of CRC in younger populations, stating that it was “still a rare thing” for younger people to develop colon cancer.

He added: “But it does happen, and I think for people who have signs of it – constipation, rectal bleeding or trouble going to the bathroom – they should get evaluated for cancer, among other conditions.”

Early screening could save lives

Oberstein offered advice on getting screened early if a patient has a family history of colorectal cancer.

“What’s really important is that people who have a family history of colon cancer – being any first-degree relative who had colon cancer at any age – that person should get screened at age 40 or 10 years before the family member’s diagnosis. So if your father had it at 45, get screened at 35.”

Dr. Nilofer Azad, who was also not involved in the research but is an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore and a member of the AACR Stand Up 2 Cancer Colorectal Cancer Dream Team said:

When you have symptoms that are consistent with a diagnosis of colorectal cancer, you should be evaluated the same way a person would be evaluated if they were 30 years older. The default should be to rule out serious conditions, including cancer, rather than making assumptions that something is not cancer or benign.”

Misdiagnosis is common

63 percent of the survey respondents reported that they had waited from three to 12 months before consulting a doctor about their symptoms, as they were not aware they might indicate colorectal cancer.

Regarding subsequent misdiagnoses, 67 percent of the survey respondents stated they had seen at least two physicians, with some seeing over four physicians before receiving a colorectal cancer diagnosis.

Limitations of the study were recognized, which included self-reported responses, the fact that the study was carried out over social media, and that further studies analyzing larger groups of patients comparing results with older patients have not yet been carried out.

The authors believe that the study “indicates that medical professionals and young adults need to be aware of the increasing incidence rate of young-onset CRC, the signs and symptoms, and the importance of timely screening when those symptoms are present, regardless of age.”

The study was announced during a media preview of the AACR Annual Meeting 2019 and will be presented at the conference itself. For more information

Source:

Young onset colorectal cancer patients are diagnosed with advanced disease after multiple misdiagnoses

https://www.news-medical.net/news/20190401/Colorecal-cancer-commonly-misdiagnosed-in-patients-under-50.aspx

MediciNova ‘excited’ by SPRINT-MS Phase 2b trial subgroup analysis results

MediciNova announced results from its subgroup analysis of the SPRINT-MS Phase 2b trial of MN-166 in progressive multiple sclerosis. This subgroup analysis was conducted based on recent feedback MediciNova received from the FDA that relapsing secondary progressive MS is different from non-relapsing secondary progressive MS as non-relapsing secondary progressive MS is the only type of secondary progressive MS without available therapy. The purpose of the subgroup analysis was to provide information about which types of progressive MS subjects responded best to MN-166 treatment in terms of the clinically significant endpoint of the risk of confirmed disability progression compared to placebo, as measured by EDSS. Confirmed disability progression was a secondary endpoint in this Phase 2b trial but would be considered a primary endpoint in Phase 3. Unlike the magnetic resonance imaging endpoint of whole brain atrophy, which is not a clinical endpoint, confirmed disability progression is the most important clinical endpoint and is the basis for FDA approval of progressive MS drugs. The trends for reduction in the risk of confirmed disability progression were highest for the subgroup of subjects with Secondary Progressive MS without Relapse, in which MN-166 demonstrated a 46% risk reduction compared to placebo as indicated by the hazard ratio of 0.538. Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc. commented, “We are excited with the results of our subgroup analysis. Although two drugs have recently received FDA approval for relapsing secondary progressive MS, there remains a very large unmet medical need for secondary progressive MS patients without relapses as there is still no drug approved for long-term treatment of these patients. Based on our extensive analysis of the SPRINT-MS data including this subgroup analysis, we are finalizing the optimal trial design for what we believe will be a very successful Phase 3 program and we plan to submit this trial design to the FDA shortly. With a convenient oral administration, a very favorable safety and tolerability profile, and the potential for better efficacy than other drugs for progressive MS, we believe ibudilast could become the best-in-disease drug.”

https://thefly.com/landingPageNews.php?id=2887074

Telehealth use surged in 2017

Telehealth use jumped 53% from 2016 to 2017, outpacing all other sites of care, according to a new report.

Telehealth utilization grew nearly twice as fast in urban than rural areas over that span, according to a new white paper from Fair Health, which parsed its database of 28 billion commercial insurance claims, the largest repository in the country. National use of urgent-care centers increased 14%, followed by retail clinics at 7% and ambulatory surgery centers at 6%, while emergency department utilization declined 2%.

Private insurance claims for telehealth services have increased more than 1,200% from 2012 to 2017, Fair Health’s data shows. Although ED utilization dropped in 2017, it still was the most-used setting.

“Telehealth has become a rather prominent source of service for mental health conditions,” said Fair Health President Robin Gelburd, adding that it has broken down the barriers to mental healthcare related to stigma and access.

In 2017, most people used telehealth for injuries like bruises and open wounds, acute respiratory infections and digestive problems. Neither injury or digestive system issues were among the top uses in 2016. Mental health, which topped the telehealth utilization list in 2016, was fifth in 2017 at 7% of claims, compared with 13% for the aforementioned uses.

Pediatric and young adults accounted for a larger share of those who used telehealth, but the age 31-to-60 demographic continued to use it the most.

Telehealth is a widely touted tool since it is often a cheaper and more convenient means to access care. More states are rolling out new laws facilitating virtual care delivery, although there are still impediments, particularly on the federal level. This can make investments in the technology inherently riskier.

“Telehealth is almost like a living laboratory as the policies and regulations get developed,” Gelburd said.

Texas, for instance, amended its state laws in 2017 to allow providers to care for patients virtually without first having an in-person meeting.

But Medicare pays for telehealth services only if the beneficiary is in a rural area with a shortage of health professionals or lives in a county outside of a metropolitan area. It also limits which providers can bill for such services.

Providers who have national licensure compacts can’t follow up with patients virtually if the individual is in a noncompact state.

“It is really the federal government,” said Dr. Jay Sanders, CEO of the Global Telemedicine Group and adjunct professor of medicine at Johns Hopkins University. “They are the ones who need to say for the Medicaid and Medicare patient population, ‘I don’t care whether you are in the inner city, a suburban or rural area, if you use telemedicine we will reimbursement you.’ “

Outside of telehealth, retail clinic claims grew 674% from 2012 to 2017, a slower pace than from 2011 to 2016. Rural and urban areas nearly matched in utilization.

Most people used retail clinics in 2017 for respiratory infections, which aligned with 2016. Those were followed by exposure to communicable diseases, general symptoms, ear infections, examinations and urinary tract infections.

Most people who used retail clinics were age 51 to 60, followed by those age 31 to 40 and pediatric patients.

“Looking at a deal like CVS and Aetna, there is a sense that retail clinics will be a very integral and a growing component of the healthcare system,” Gelburd said.

Still, there is some progress to made in both retail and urgent-care settings regarding communication, staffing levels and data sharing to ensure care isn’t duplicated, she said.

For urgent-care centers, utilization grew 1,434% from 2008 to 2017, more than seven times that of EDs. Growth in urgent-care use from 2008 to 2017 was slightly higher in rural than in urban areas. But from 2016 to 2017, growth was flat in rural areas compared with 15% in urban areas.

As in retail clinics, acute respiratory infections were the most common diagnostic category in urgent-care centers in 2016 and 2017. Those were followed by general symptoms, sprains, strains, breaks and fractures, joint/soft tissue issues, UTIs, other injuries, and ear infections.

The age 31-to-40 demographic used urgent care the most, followed by pediatric patients. The average charge of a 15-minute visit was about $60 less at a retail clinic than at an urgent-care center.

One can get a good sense of how care is evolving by looking at the distribution of claims by diagnosis, Gelburd said.

Retail clinics were predominantly used for vaccines. They are now used more like primary-care outposts for ear or respiratory infections. Telehealth, which was mostly used for mental health and dermatology, is now seeing more respiratory and digestion cases, she said.

“We are seeing the evolution in real time and the broadening and blurring of lines between different types of venues,” Gelburd said.

https://www.modernhealthcare.com/care-delivery/telehealth-use-surged-2017

CMS finalizes Medicare Advantage pay raise, ups encounter data use

Medicare Advantage plans are getting a pay raise and more flexibility to tailor benefits for chronically ill patients next year, the CMS said Monday. But Advantage plans’ payments will also be based on a higher percentage of patient “encounter data,” a change that health insurers have fought hard to avoid.

The CMS on Monday finalized a rule giving Medicare Advantage plans a 2.53% pay raise in 2020. The agency had initially floated giving plans a 1.59% pay bump for next year. The final rate is less than the 3.4% raise Advantage plans received for 2019, which was one of the biggest pay raises plans have received in years.

“These changes to the model better reflect costs and improve the financing for the care of beneficiaries with multiple conditions,” CMS Administrator Seema Verma said in a press call with reporters late Monday.

The final rule also allows Medicare Advantage plans more flexibility to offer supplemental benefits to patients with chronic illnesses that aren’t necessarily going to cure their conditions but that will address the social and environmental factors that can harm health. Plans will also be able to tailor benefits or reduce cost-sharing to meet a certain members’ needs.

For instance, Verma said a Medicare Advantage plan could pay for home air filters or carpet shampooing for a patient with asthma, or pay for heart-healthy meals for a beneficiary with heart disease. She noted that in the original Medicare program, 27 million people have chronic conditions. The agency also said it is encouraging plans to take advantage of the flexibilities to offer targeted benefits to patients with chronic pain or those undergoing addiction treatment.

With this new flexibility, “Coverage is determined by what a person needs, not just what’s on a list of allowable items or services,” Verma explained.

The change, which was called for by the Bipartisan Budget Act of 2018 is a significant departure to previous policy, which allowed coverage only for services that prevented, improved or cured a patient’s conditions. Previously, plans were also barred from offering different benefits to different sets of patients. The CMS began introducing flexibility starting in 2019 by allowing plans to pay for in-home supports, such as grab bars and wheelchair ramps, for their plan members.

In comments to the CMS due in March, health insurers largely supported the increased leeway in what supplemental benefits they could offer patients. But most of them railed against the agency’s proposal to increase the amount of encounter data it uses in calculating patient risk scores to 50% from 25%, saying encounter data is often inaccurate and will lead to lower funding for the plans.

The CMS didn’t back down. Verma said the agency has been monitoring encounter data and feels comfortable moving ahead with plans to increase its use in the risk-adjustment model “because of the work we’ve done with the plans around improving the accuracy.”

Federal payments to Medicare Advantage plans are adjusted based in part on patient risk scores. Generally, the sicker the person, the higher the risk score and, consequently, the higher the payment an Advantage plan receives. Plans have been accused of manipulating risk scores to nab higher payments, however.

The CMS has been using encounter data to calculate risk scores since 2016, but insurers have never embraced it. In a letter to the CMS in March, Cigna Corp. even said it was concerned the agency “may be using the EDS transition to reduce MA payments without providing full information about the impact to stakeholders and others.”

Beyond encounter data, the CMS also said it is moving ahead with plans to adjust payments to reflect patients’ total number of medical conditions, in addition to viewing each condition individually. This change is required by the 21st Century Cures Act. The CMS said it will implement what it called the “alternative payment condition count model,” which accounts for some additional diagnoses, including dementia and ulcers. Insurers had supported the alternative model in their comments to the CMS.

https://www.modernhealthcare.com/payment/cms-finalizes-medicare-advantage-pay-raise-ups-encounter-data-use

AACR 2019 – Vitrakvi relapse findings justify Bayer’s interest

The Vitrakvi follow-on LOXO-195 yields results backing both the rationale behind its development and Bayer’s decision to take on full rights.

The approved TRK inhibitor Vitrakvi did not play a big part in Lilly’s $8bn takeout of its maker, Loxo, but the drug is a focus for Bayer, Loxo’s longer-standing partner. The related project LOXO-195 is at least as important for the German group, and clinical results unveiled today at the AACR meeting have underlined its value.

LOXO-195 is also a TRK inhibitor, but has been designed to work in patients who have relapsed on Vitrakvi or Roche’s rival, entrectinib, despite carrying a TRK kinase mutation. The AACR data back the hypothesis that LOXO-195 works in these subjects but not in others who relapse in different ways after first-line TRK therapy.

They come from 29 evaluable post-TRK-inhibitor subjects, derived from a phase I study and US compassionate-use programme. 20 of these patients had some kind of residual TRK mutation, but the rest either did not, or their status was unknown.

The overall remission rate in the 20 TRK mutants was an impressive 45%, said the lead investigator, Dr David Hyman, from Memorial Sloan-Kettering Cancer Center. The one caveat was that the data come from investigator assessment, and have not yet been independently reviewed.

But the results build on case reports, published in Cancer Drug Discovery back in 2017, in just two subjects who had progressed after Vitrakvi and had what is termed a Solvent Front mutation. Both developed partial responses after treatment with LOXO-195, it was reported.

What LOXO-195 did not demonstrate in the results presented at AACR further backs up the hypothesis behind its development. Namely, none of the three subjects with an identified bypass mechanism, meaning that TRK signalling was no longer driving the cancer, responded to LOXO-195.

LOXO-195 PHASE I (NCT03215511) & COMPASSIONATE-USE DATA
	Subjects	ORR
TRK resistance mutation	20	45%
Solvent Front	14	50%
Gatekeeper	4	25%
xDFG	2	50%
Unknown/other*	9	11%
Total	29	34%
Source: AACR; *3 identified bypass, 1 no identified TRK mutation or bypass alteration, 5 unknown.

Lilly acquired Loxo earlier this year, largely for its Ret kinase inhibitor LOXO-292. As soon as the deal closed Bayer exercised a change-of-control option, giving the German group full development rights to Vitrakvi and LOXO-195, which it now calls BAY 2731954.

It is interesting that Ignyta, maker of the rival TRK inhibitor entrectinib, also fell prey to a takeover, by Roche, although the focus of this deal was probably not TRK but Ros1, a mutation that Vitrakvi does not target. Entrectinib is now awaiting US approval.

Vitrakvi’s approval made the drug the second to get a green light irrespective of tumour type. Dr Hyman said TRK mutations were responsible for just 0.5% of all US cancer cases, but that many of these responded to Vitrakvi treatment.

He stressed that the AACR data suggested that LOXO-195 could eventually become a meaningful treatment for subjects whose cancers are resistant to first-generation TRK inhibitors. Bayer will no doubt be keen to point out that one such drug is entrectinib.

https://www.evaluate.com/vantage/articles/events/conferences/aacr-2019-vitrakvi-relapse-findings-justify-bayers-interest

AACR: Apexigen, BMS steal the show with promising I-O combo in pancreatic cancer

Last August, tiny California biotech Apexigen revved up its pipeline with a $73 million venture roundthat allowed it to move its lead immuno-oncology candidate into clinical trials. Now, it’s rolling out early data from that research that are turning heads at the annual American Association for Cancer Research (AACR) meeting in Atlanta.

Apexigen is testing a combination of its CD40-activating antibody with Bristol-Myers Squibb’s PD-1 inhibitor Opdivo and chemotherapy in patients with advanced pancreatic cancer. At AACR, they announced that the combination shrunk tumors in 20 out of 24 patients that could be analyzed in an interim review of a phase 1b study. The results were so encouraging that the trial has moved to phase 2, the presenters said.

Apexigen’s immuno-oncology drug candidate, APX005M, was designed to stimulate several elements of the immune system so that it’s better equipped to recognize and fight cancer. The company’s strategy is to combine it with other I-O treatments in cancer. Toward that end, it is collaborating with several drug developers in addition to BMS including Boehringer Ingelheim and Johnson & Johnson’s Janssen.

In the trial described at AACR, half the participants are receiving chemotherapy plus APX005M and half are getting that combo plus Opdivo. Most of the patients experienced side effects, but several were able to stay on the regimen for about a year, said investigators from the University of Pennsylvania, one of the clinical trial sites, during the AACR presentation.

“We are very excited about the encouraging data so far, especially because metastatic pancreatic cancer has a five-year survival rate of less than 9 percent, making it an area of high unmet medical need,” said the Parker Institute’s Chief Medical Officer Ramy Ibrahim, M.D., in a statement.

The AACR announcement marked the first clinical data out of a study funded by the Parker Institute for Cancer Immunotherapy, which was founded in 2016 by Facebook billionaire Sean Parker. The institute developed the trial in collaboration with the I-O focused nonprofit Cancer Research Institute.

Apexigen is one of many biotechs focused on expanding the potential market for immune checkpoint inhibitors—and BMS has been more than happy to oblige with Opdivo. Its flagship I-O drug has struggled to compete in the market against Merck’s blockbuster Keytruda, which has proven effective in several cancer types, including most recently kidney cancer.

BMS did celebrate one other success at AACR this past weekend, announcing data from a phase 2 study showing that a combination of Opdivo and its other checkpoint inhibitor Yervoy performed well in patients with high-grade neuroendocrine tumors.

Apexigen, meanwhile, is eager to test combinations of Opdivo and APX005M in other cancers. Last summer, it said it was enrolling a phase 1 trial that will combine the two drugs along with cabiralizumab, an anti-CSF-1 antibody that BMS is developing with Five Prime Therapeutics. That trial is enrolling patients with lung cancer, melanoma and kidney cancer.

The Parker Institute’s Ibrahim believes the pancreatic cancer trial presented at AACR will benefit not only Apexigen’s other trials, but multiple other I-O combinations being tested around the world. “What we learn in this trial can inform the work being done on other solid tumor types, so that we can make immunotherapy beneficial for more patients,” Ibrahim said.

https://www.fiercebiotech.com/research/aacr-apexigen-bms-steal-show-promising-i-o-combo-pancreatic-cancer

Settlement set to sling Soon-Shiong out of biotech investment

Patrick Soon-Shiong’s NantCell could lose its controlling stake in Precision Biologics through a legal settlement. The proposed settlement would effectively erase NantCell’s investment to clear up a case alleging Soon-Shiong improperly withdrew $47 million from Precision Biologics.

The case, details of which were reported by Law360, dates back to October 2015. That month, NantCell revealed it had paid $50 million to take a controlling stake in Precision Biologics, a startup working on antibodies to treat solid tumors.

Soon-Shiong framed the investment as part of the growing portfolio of programs intended to treat and diagnose cancer operating under his NantWorks umbrella. The investment has become better known for the legal case it triggered, though.

The case centers on the allegation that Soon-Shiong, NantCell and two related people on the board of Precision Biologics withdrew $47 million within 30 days of the $50 million investment. A Precision Biologics shareholder argued the withdrawal breached an investor rights agreement and the fiduciary duties of Soon-Shiong and his co-defendants.

Aspects of the case against Soon-Shiong fell away last year, but he is yet to escape the breach-of-duty claims. To resolve those outstanding allegations, the two sides have have spent more than a year discussing a potential settlement.

Now, details of the agreement have emerged. The settlement would effectively wind back the clock to before the NantCell investment. NantCell would return its stake in Precision Biologics, which, in turn, would hand back all the money it has left from the investment. NantCell would put $2.5 million into a fund shared by certain Precision Biologics shareholders.

The shareholders and defendants filed the settlement in the belief that “the terms contained in this stipulation are fair, adequate and in the best interests of plaintiff, the class and defendants, and it is reasonable to settle the action.” The defendants are not admitting wrongdoing.

Controversy has dogged Soon-Shiong in recent years. NantCell’s acquisition of Altor BioScience spawned lawsuits, including a case brought by Cher, and accusations of “looting.” Another part of the Nant portfolio, NantHealth, faces lawsuits alleging it made “material misstatements and omissions in violation of the federal securities laws” in relation to its IPO and could be delisted from Nasdaq.

https://www.fiercebiotech.com/biotech/settlement-set-to-sling-soon-shiong-out-biotech-investment