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Saturday, June 2, 2018

The Unappreciated Key to Success


The most unappreciated element in success in any area of life–trading or otherwise–is the capacity to sustain effort.  We can think of this capacity as intentionality:  the ability, over time, to exercise free will.
For much of daily life, we follow routines.  This is efficient, allowing us to get the most done with the least effort.  A great example is driving a car.  Being able to do that automatically enables us to carry on conversations, listen to music or podcasts, etc. The problem occurs when we become so immersed in routine–so wedded to getting the most done with the least effort–that we are unable to sustain the efforts that generate distinctive performance.
Important research from the psychologist Mihalyi Csikszentmihalyi identified a “flow state” in which people become capable of high levels of creativity.  The flow state results from being immersed in efforts over time–a kind of hyperfocus.  In that state of superfocus, we become capable of processing information in new ways, seeing patterns and solutions that escape us in our normal state of awareness.
In our ordinary state of mind, we can only achieve ordinary things.  All success comes from the ability to transcend routine.  But that requires effort and the capacity to sustain effort.  Successful people have developed routines that exercise intentionality:  that build the capacity to sustain flow states.  They sustain those efforts by pursuing their strengths: what they are good at and what speaks to them.  We achieve hyperfocus when we are hyper-interested in what we are doing.  If you need discipline to get things done, you know you are not operating in the sphere of your strengths and passions.

Dimon: Health insurers griped to him on Amazon-Berkshire deal


  • Dimon says that irate healthcare companies called him to complain about joint venture
  • Healthcare effort has a 20-year horizon and seeks to lower costs, improve service, he says
  • Dimon: “They’re going to tell me I can’t do a better job for my employees? Isn’t that what they’re supposed to help me do anyway?”
J.P. Morgan Chase CEO Jamie Dimon has been on the receiving end of some testy phone calls recently.
After he and fellow billionaires Amazon‘s Jeff Bezos and Berkshire Hathway’s Warren Buffett announced the formation of a joint venture in January to reduce medical costs for their three companies’ 1.5 million insured employees, several healthcare-related providers reached out to Dimon personally, he said Friday during a New York conference.
“Quite a bit of them were pissed off, which kind of pissed me off,” Dimon, 62, said. “They’re going to tell me I can’t do a better job for my employees? Isn’t that what they’re supposed to help me do anyway? That’s all we’re trying to do, is do a better job for the health of our employees.”
The effort, spearheaded by Berkshire Hathaway executive and J.P. Morgan board member Todd Combs, has yet to settle on a CEO. After that happens, the venture will begin testing ideas to attack the myriad problems related to the rising costs of American healthcare, Dimon said. When the effort was announced January 30, the shares of pharmacy benefit managers, heath insurers and biotechnology companies all slumped.
The effort has a 20-year horizon and seeks to partner with companies within the healthcare ecosystem, Dimon said. Among issues to tackle are related to use of data, lack of consumer choice, high costs related to fraud and administrative costs, end of life care, and lifestyle-related diseases, he said.
“They could attack it one drug at a time, they could attack chronic care, they could attack emergency rooms,” Dimon said. “There will be things we will come up with that we couldn’t possibly think of today that will hopefully make it much better.”

Foundation Med, Partners at #ASCO18 on Comprehensive Genome Profiling, Cancer


 Foundation Medicine, Inc. (NASDAQ:FMI) announced that new data generated from its comprehensive genomic profiling (CGP) assays will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting from June 1-5, 2018 in Chicago. The company and its collaborators will present a total of 28 studies, including two oral presentations. Highlights of these presentations include:
  • studies demonstrating the importance of known and novel genomic biomarkers of immunotherapy response, including tumor mutational burden (TMB), microsatellite instability (MSI) and PBRM1 alterations across a diverse range of cancer types that could inform more precise use of these treatments;
  • new data from PURE-01, a phase II study evaluating neo-adjuvant pembrolizumab in urothelial bladder cancer demonstrates the ability of CGP to detect genomic biomarkers (RB1PBRM1 and TMB) when combined with T-cell inflammation signatures to potentially predict response to immunotherapy;
  • new data showing that high tissue TMB is associated with higher likelihood of response and longer duration of response to atezolizumab in non-small cell lung cancer, metastatic urothelial carcinoma and melanoma;
  • data from FoundationACT® liquid biopsy assay, describing the landscape of kinase fusions and rearrangements from ctDNA in more than 9,000 clinical cases across multiple cancer types; and
  • updated data from the precision oncology I-PREDICT clinical trial showing improvements in patient outcomes with integration of molecular tumor boards informed by CGP into treatment planning.

New Wave in Neurology/Stroke Care


Andrew N. Wilner, MD: Welcome to Medscape. I am Dr Andrew Wilner, and I am at the 2018 American Academy of Neurology (AAN) meeting in Los Angeles. I have the pleasure to be joined by Dr Terry Detrich. Dr Detrich has been a frequent attendee at the AAN meetings and is still in practice.
Thanks for joining me, Terry. I would like to talk with you about the AAN meetings and have you share your insights on how the meeting has changed over the years, in particular with respect to its value to neurologists.
Terry P. Detrich, MD: Thank you for having me.
Wilner: When we spoke last night, I could see how very excited you are about the meeting.
Detrich: Every time I attend an AAN meeting, there is new information that changes my practice. I am very patient-oriented, and when I attend these meetings, I look for information that will enhance the care of my patients.
I see myself as a buffer between unrealistic and realistic [patient] expectations and reality. When things change—and they are changing rapidly—I want to be part of these changes, incorporate them into my practice, and deliver the latest care recommendations to my patients as soon as possible.
I have been very active in the management and treatment of stroke, and I just recently retired as medical director of a stroke center at a small rural hospital. Following the approval of tissue plasminogen activator (tPA), my colleagues and I have been very successful in treating stroke patients. I was actually with Michael Walker, MD, at the 1995 AAN meeting in San Francisco when he and his colleagues presented the tPA data. This [treatment] changed my life and the lives of my patients; it also changed our hospital’s healthcare delivery system.
For a primary hospital, my institution has been incredibly successful in its care of stroke patients. Our hospital system sees approximately 225 stroke patients a year. This past year, we won the American Heart Association/American Stroke Association Get With The Guidelines-Stroke Gold-Plus Quality Achievement Award for stroke care, and our use of tPA has gone up substantially owing to the support of our emergency physicians. My institution is affiliated with the University of Maryland, which helped us with [stroke care] coverage.
The MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands)[1] was the beginning of the changes in stroke care. Yesterday, the data that were presented fromthe DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention)[2] and the DEFUSE 3 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 3)[3] trials provided a new perspective on stroke care delivery.
Wilner: These trials suggest that thrombectomy now can be performed up to 24 hours after an ischemic stroke—a new wave of ways to help patients.
Detrich: It is an incredible new wave of care. There will be a lot of growing pains in implementing these new changes to stroke care, and we have already begun to address some potential problems in this regard at my institution.
For example, we cannot send all stroke patients to a tertiary facility—there are not enough beds to do so. At our institution, located in a small town in Maryland, we are going to select our patients, prestudy them, and move the transfer through the use of telemedicine. We have a great transport system, in part based on our shock-trauma unit, which I believe was the first in the country. We have an extensive medical evacuation system already in place, and are ultimately looking at a telemedicine program. We have not been able to expand in the way that I would like in regard to telemedicine, but I have the whole medical team on board, thanks in part to the great coordinators with whom I work.
We also will need advanced imaging modalities to assess perfusion or perfusion/diffusion mismatches to determine which patients require transport to a tertiary center.
As I mentioned, we are very big on administering tPA to stroke patients and have had outstanding treatment successes. This past year, I believe all of our stroke patients received tPA within 60 minutes We are thrilled with and proud of our achievements.
For 20 years, there were no changes in stroke care. I did not even bother to go to any of the stroke sessions at the AAN meeting. My perspective changed when the tPA data were presented. Now I always attend the stroke sessions to keep up with the latest trial data, the direction care is heading, and the latest standard of care.
I am overwhelmed by the data [from DAWN and DEFUSE 3] and the impact these will have on our patients over the next few years. I do have concerns about the increasing cost, an issue that also was raised by others yesterday. Providing 24/7 care for patients is a big deal. We do not have enough stroke doctors or stroke trainees to offer this type of coverage. Another concern related to cost is specifically who is going to pay for this care.
Although the selected group of patients in each of the two trials was small, the outcomes were spectacular.[2,3] These outcomes may be compared with studies showing the effectiveness of catheterization in preventing myocardial infarction (MI). It took 22 patients to get a catheter study to prevent an MI to have dramatic improvement in stroke in this selected group.
With respect to the DAWN and DEFUSE 3 trials, we have to keep in mind that the results were seen in a selected group of patients. It was between two and three patients to get outstanding results. These outstanding results were that the patients were alive and had a modified Rankin scale score of 2 or less, indicating at least self-care or even the ability to return to work and function normally. That is pretty outstanding.
Wilner: What other information from the AAN meeting are you going to share with your patients?
Detrich: I was blown away by the results of some of the gene-modifying trials that were reported. I had an off-label, anecdotal conversation with some of my colleagues in the genetics field about their experiences with gene modification for Huntington disease and amyloid beta modification. I have patients with amyloid disease and patients with Huntington disease, so [I was excited] to hear these anecdotal reports on the possibility of genetic modification in Friedreich ataxia.
I thought these research findings would take 20 years, which was a realistic expectation when I started in practice. Now things are happening so quickly. With all the basic science, with all the technical advances, with all the experience, this has come about in a matter of 2-3 years from what was postulated.
It is great to have this type of data to share with patients. In fact, I have an informal discussion scheduled in May to talk with staff, patients, and caregivers about what is new in neurology. I am thrilled to talk about this with them.
Wilner: With your level of interest and enthusiasm, I do not see retirement in your near future.
Detrich: Well, I retired from private practice, but am working full-time. In my practice, I focused more on what I will call “geriatric neurology,” though more on movement disorders and dementias.
In addition to the changes that are taking place in diagnoses [of neurologic diseases], new therapies are not that far away. We are finally at a point where we are sorting through all these conditions.
I am an old man who has been in practice for a long time. Now, after all of the information presented at the AAN meeting, I am rethinking Parkinson disease. For example, I no longer view Parkinson disease as a dopamine deficiency disease, but rather as an alpha-synucleinopathy. This perspective explains a lot of my clinical observations. I am both thrilled and excited to share some of this new information with my staff and my patients and their caregivers.
Wilner: Dr Detrich, I share your enthusiasm, and that is also why I attend the AAN meetings. Now that we have tools to help our patients, I think more and more physicians are going to stay in practice longer. We finally have the ability to help patients and change the ill-deserved reputation that neurologists had a long time ago.
Detrich: I can talk about that too, because I was there a long time ago and remember the “diagnose and adios” reputation we had. As you know, the decade of the brain in the 1990s changed neurology from being a diagnostic specialty to a therapeutic specialty. I was very enthusiastic and excited about this. The big thing then, when we look at the long term, was disease-modifying therapies in multiple sclerosis.
I was very hopeful in the 2000s, but became a little frustrated in early years of the 2010s. Now, with all this new information, technology, and potential new treatments over the past couple of years, I am rejuvenated, anticipating that next step at the bedside. There are actually ongoing clinical trials for tau and for alpha-synuclein. I want to be part of that, which is why I want to continue to practice.
Wilner: I want to thank Dr Detrich for joining me here at the annual AAN meeting in Los Angeles. I am Dr Andrew Wilner, reporting for Medscape.

Adaptimmune: #ASCO18 presentation data further supports med benefit


Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, presented initial data from the ongoing pilot study of NY-ESO SPEAR T-cells in myxoid/round cell liposarcoma (MRCLS). With eight patients treated, the best overall responses include three confirmed partial responses, one unconfirmed partial response, three stable disease, and one recently treated patient awaiting assessment. These data were presented during an oral presentation by Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center at the American Society of Clinical Oncology (ASCO) annual meeting.
GlaxoSmithKline plc (LSE:GSK) (NYSE:GSK) exercised its option to exclusively license the right to research, develop, and commercialize the NY‑ESO SPEAR T-cell therapy program in September 2017. Transition of this program to GSK is ongoing.
“We continue to see responses in patients with advanced MRCLS who have failed previous standard chemotherapy,” said Rafael Amado, Adaptimmune’s Chief Medical Officer. “We observe significant proliferation of our SPEAR T‑cells in peripheral blood, and infiltration into metastases that were previously devoid of inflammatory cells. These findings bode well for a broad therapeutic potential of SPEAR T‑cells across multiple solid tumors.”
Data Update from the Ongoing NY-ESO MRCLS Study
During an oral presentation on June 2nd entitled, “Pilot Study of NY-ESO-1c259T Cells in Advanced Myxoid/Round Cell Liposarcoma,” Dr. D’Angelo presented an update from this ongoing study (data cut-off May 23 2018).
  • Responses:
    • Best overall responses include 3 confirmed partial responses, 1 unconfirmed partial response, 3 patients with stable disease, and 1 recently treated patient awaiting assessment
    • There is an overall trend in tumor burden decrease among the majority of patients
    • The tumor burden decrease across target lesions ranged from 16.9% to 50%
    • Three patients have now progressed
  • Safety: Thus far, data indicate that NY-ESO SPEAR T-cells remain generally well tolerated in this patient population:
    • There was one event of cytokine release syndrome (CRS) ≥ Grade 3, which was characterized by fever, hypotension, rash, headache, and supraventricular tachycardia. The patient was treated with tociluzumab. The CRS resolved six days post-infusion.
    • There were four SAEs reported by three patients:
      • Grade 3 CRS (noted above), which resolved
      • Two Grade 2 events of CRS, both of which resolved
      • Grade 2 pleural effusion, which improved with treatment and the patient was subsequently discharged from hospital
    • Most adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or cancer immunotherapies
  • SPEAR T-cell persistence: Although data are preliminary, there appears to be a correlative trend between SPEAR T-cell persistence and response.
The Company will host a live teleconference to answer questions about the updated safety data on June 4, 2018 at 8:00 a.m. EDT (1:00 p.m. BST). The live webcast of the conference call will be available via the events page of Adaptimmune’s corporate website at https://bit.ly/2shwniM. An archive will be available after the call at the same address. To participate in the live conference call, if preferred, please dial please dial +1-(833) 652-5917 (U.S.) or +1-(430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (9199456).

Immunotherapy for Frail Adults With Common Malignancies: #ASCO18


Although immunotherapy drugs may now provide a treatment option for older patients with cancer who are ineligible for, or whose disease fails, chemotherapy, there are many unanswered questions about the efficacy and adverse effects of immunotherapy in this patient population. Highlighting these knowledge gaps, as well as discussing ways to reconcile those gaps in clinical practice, will be the focus of an Education Session on June 4 titled “Treating Frail Adults With Common Malignancies: Best Evidence to Personalize Therapy.”*
“People should come to the session to get a deep dive into the current existing evidence base for older or more vulnerable adults who are receiving immunotherapy,” said session Chair Ronald J. Maggiore, MD, of the University of Rochester Medical Center. Older adults are often not candidates for standard chemotherapeutic treatments because of comorbidities and poor performance status, Dr. Maggiore said.
The session will focus on non–small cell lung cancer (NSCLC), which Dr. Maggiore will discuss, as well as bladder cancer and lymphoma. The session will also cover immunotherapy recently approved by the U.S. Food and Drug Administration (FDA) for these cancer types, including pembrolizumab for patients with bladder cancer, Hodgkin lymphoma, and NSCLC.1
However, the clinical trials that led to many of the immunotherapy drug approvals included younger patients than oncologists typically see, Dr. Maggiore said. Most of the patients enrolled in the seminal studies of immunotherapy for NSCLC were in their early to mid-60s, yet 50% of patients diagnosed with lung cancer in the United States are older than 70.2 These trials also excluded patients with poor performance status from participation a priori,3,4 although post-marketing and FDA safety analyses have been somewhat encouraging for single-agent checkpoint inhibitors in older adults or those with poorer performance status, Dr. Maggiore added.
It can be challenging to apply data from these trials to clinical decision-making for older patients, particularly if they have other comorbidities, Dr. Maggiore said. One of the issues is that, as patients age and develop comorbidities, immune function may decline and there may be changes in the tumor microenvironment, all of which could affect the efficacy of immunotherapy drugs.
The session will feature a clinical vignette to illustrate some of the key challenges in deciding how to treat older patients with immunotherapy, Dr. Maggiore said.

Older Patients in Advanced Bladder Cancer Trials

Dr. Ravindran Kanesvaran
During his presentation, Ravindran Kanesvaran, MD, of the National Cancer Centre Singapore, will discuss the characteristics of older patients with advanced bladder cancer who could benefit from immunotherapy drugs.
Patients who are frail or who have poor renal function are ineligible for cisplatin-based chemotherapy, which is the standard of care for advanced bladder cancer. “Thanks to immunotherapy, patients who may not have received the current standard of care can potentially get some treatment that can prolong their life and give them good quality of life,” Dr. Kanesvaran said.
The recent approvals of pembrolizumab and atezolizumab in the first-line treatment of patients with advanced bladder cancer who were cisplatin-ineligible were based on single-arm phase II clinical trials that reported good tolerability and antitumor activity. 5,6 Moreover, because trial participants were ineligible for cisplatin treatment because of poor performance status or comorbidities such as kidney dysfunction, neuropathy, or hearing loss, they tended to be elderly (median age: 74 and 73 years for the pembrolizumab and atezolizumab studies, respectively).
“Now we know these data specifically apply to older patients with advanced bladder cancer. In general, clinical trial enrollments are biased toward younger populations, and it is a challenge to decide how to extrapolate those data to the older patient,” Dr. Kanesvaran said.

Immunotherapy for Older Patients With Lymphoma in the First-Line and Relapsed Settings

Dr. Raul Cordoba
As is the case with most cancer types, clinical trials of immunotherapy drugs for Hodgkin and non-Hodgkin lymphoma have included few patients older than 65. Raul Cordoba, MD, PhD, MS, of the Fundacion Jimenez Diaz University Hospital, in Madrid, Spain, will review data on PD-1 inhibitors and CAR T-cell therapy for patients with aggressive relapsed lymphoma.
“So far, clinical data on efficacy and safety of immunotherapy in older patients with lymphoma seem to be similar to younger patients, but we need longer follow-up,” Dr. Cordoba said. Research should be conducted to understand the relationship between baseline immune function, as evaluated through a comprehensive immune assessment, and outcomes of immunotherapy in older patients, he said.
Dr. Cordoba will also discuss early clinical studies testing combination nivolumab and brentuximab vedotin as first-line treatment of patients with advanced Hodgkin lymphoma. “This strategy seems to be attractive in older patients with Hodgkin lymphoma who are not candidates for conventional chemotherapy because of frailty or comorbidities,” Dr. Cordoba said.
–Carina Storrs, PhD
*Program information updated as of February 22. For session time and location information, please refer to the ASCO iPlanner on the Attendee Resource Center (am.asco.org/arc).

ASCO Aims to Reduce Obesity Risk for Cancer #ASCO18


Obesity is a major public health issue in the United States, and the rates have risen dramatically since 1990.1 In many states, 36.5% of adults and 17.0% of children and adolescents are obese.2  Obesity contributes to major noncommunicable diseases including cardiovascular disease, diabetes, and cancer, both in terms of risk and mortality. As many as 84,000 cancer diagnoses each year are attributed to obesity, and overweight and obesity are implicated in 15% to 20% of total cancer-related mortality.3
Obesity is also associated with a worse prognosis after a cancer diagnosis and may negatively affect the delivery of systemic therapy, contribute to the morbidity of cancer treatment, and raise the risk of second malignancies and comorbidities.3
ASCO has been raising awareness of the connections between obesity and cancer risk and outcomes since 2013 when the Energy Balance Work Group was developed to evaluate the evidence and generate recommendations for the role ASCO should take in these areas. Despite the strong connections between obesity and both cancer risk and cancer outcomes, most Americans are unaware that obesity will increase their risk of developing or dying from cancer.
Dr. Jennifer Ligibel
Dr. Clifford Hudis
“When we started this effort, the goals were to make the oncology community more aware of the connection between obesity, inactivity, and cancer risk, and find ways to help providers talk to patients about this,” Jennifer A. Ligibel, MD, of the Dana-Farber Cancer Institute, said. “The research shows that when people are diagnosed with cancer, they are more open to changing their lifestyle and losing weight, which makes this a teachable moment.”
“There was growing evidence from basic and translational science that obesity was a contributing factor to various cancers,” ASCO Chief Executive Officer Clifford A. Hudis, MD, FACP, FASCO, said.
This motivated ASCO’s Board of Directors in 2013 to “elevate the issue of obesity strategically and put ASCO resources to work in addressing it,” Dr. Hudis said. The board’s strategic obesity initiative focused on raising public awareness, research, policy, and advocacy.
In October 2017, as a result of the continued need for ASCO’s involvement in obesity awareness and prevention, the temporary Energy Balance Work Group became the Obesity and Energy Balance Subcommittee, a permanent branch of the Cancer Prevention Committee. Dr. Ligibel, who chairs the subcommittee, told the ASCO Daily News that the subcommittee met in December 2017 to “consider where ASCO should focus its efforts in this area, and how ASCO’s unique role representing oncology professionals could have the biggest influence in reducing the impact of obesity on cancer risk and outcomes.”
The Obesity and Energy Balance Subcommittee developed plans for a number of new initiatives over the next few years, including:
  • A survey of ASCO members to determine whether they are discussing physical activity and weight management with patients during and after cancer treatment, and to identify tools and resources that could help support oncology providers in these discussions;
  • Development of guidelines that would incorporate physical activity, weight management, and dietary intake at different points during the cancer trajectory; and
  • Development of initiatives to educate oncology professionals at all career stages about the relationship between obesity and cancer, as well as strategies to help patients lose weight and make other lifestyle changes during and after treatment.

ASCO’s Previous Obesity Efforts

ASCO’s new initiatives to combat obesity build upon an already robust effort by the Society. For example, in recognition that a broad-based collaboration needed to tackle this public health crisis, ASCO hosted the Summit on Addressing Obesity Through Multidisciplinary Collaboration in 2016. “We brought different professional organizations together that have been working in this area to look at where we can synergize and harmonize our efforts. We realized that by coordinating our efforts, we could avoid duplication, reach a broader audience, and have more of
an impact than working on our own,” Dr. Ligibel said.
The subcommittee’s efforts were in addition to the resources and events developed by the original Energy Balance Work Group in 2014, including:
  • ASCO’s “Position Statement on Obesity and Cancer,” published in the Journal of Clinical Oncology (JCO). The statement outlines ASCO’s interest in obesity and cancer, its priorities, and its initiatives to increase awareness of the links between obesity and cancer.3
  • The Obesity Toolkit, designed to educate oncologists and patients about the role weight management and healthy lifestyle behaviors play in cancer. The toolkit was updated in 2015 and has been translated into Spanish and French. For more information, visit asco.org/obesity.
  • ASCO’s Research Summit on Advancing Obesity Clinical Trials in Cancer Survivors, held in 2014 to identify the unmet needs and opportunities for research regarding obesity, weight loss, and cancer. “Most of the research studies up to this point have been observational. We looked at what types of additional data will be needed to establish weight loss and physical activity as a standard part of cancer care,” Dr. Ligibel said. The recommendations from the summit were published in JCO in November 2015.4
“ASCO has recognized that obesity is an area of increasing research. Having high-quality research will enable us to determine what policies we should advocate for on behalf of our patients with cancer and enable oncology providers to give patients evidence-based information to make the necessary lifestyle changes to reduce obesity,” Dr. Ligibel said.
–Christine Lehmann, MA