3 Questions on…
Answers straight from the experts on the latest news and topics in oncology
Thursday, August 07, 2014
With RICHARD L. SCHILSKY, MD, FACP, FASCO, Chief Medical Officer of the American Society of Clinical Oncology
One of the biggest challenges to making personalized cancer care a reality is understanding the potential of targeted drugs outside of their approved indications, Richard L. Schilsky, MD, FASCO, Chief Medical Officer of the American Society of Clinical Oncology, said in a phone interview. He explained the key components of a new ASCO initiative to do just that.
“It’s becoming more and more common to recommend molecular profiling — particularly for patients who have advanced cancer or patients who’ve exhausted all standard treatment options — to determine whether or not those results might suggest a course of therapy for the patient to try,” he said. “But many of those drugs would have to be used off-label, or would only be available in a clinical trial. The problem becomes — how does the patient get access to the drug? And, even if the doctor can get access to the drug and treat the patient, the rest of the medical community has no way of understanding whether that particular approach actually worked in that patient with those characteristics or not.”
The program proposed by ASCO — and now currently being developed by a steering committee — would capture data from real world clinical use of those drugs, and at the same time create incentives that would facilitate easier patient and physician access to those drugs.
“The point is to try to solve how to simplify access to the drug, and also how to learn from the experience of using the drug off-label so that ultimately we can gain more information about whether those approaches are worthwhile to pursue or not,” Schilsky said.
He presented the idea at an American Cancer Society Cancer Action Network forum in April (OT 6/25/14 issue), and he said ASCO plans to launch the program early next year. (The program has not been formally named but is being referred to as the national access program.) Schilsky also outlined the program in a recent Nature Reviews Clinical Oncology Perspectives article (2014;11:432-438).
He spoke to OT about how and why this initiative would lead to better cancer care.
1. How would the program work?
“The program would make drugs available to patients who are willing to enroll in a prospective observational registry study. The patients would need to be enrolled in a protocol that would be similar to a clinical trial — having both eligibility and exclusion criteria, though fairly liberal — and would need to consent to have their outcomes collected so that data could be incorporated into a registry. And, we hope to enlist the interest and support of a number of pharmaceutical companies who would be willing to make some of their marketed, targeted anticancer drugs available at little or no cost to patients through this program — similar to the way they might make drugs available for an expanded access program
“The doctor treating the patient — if they believe that a molecular profiling test is medically appropriate — would have such a test performed (by whatever mechanism they would order such a test). And after reviewing results would determine whether or not one of the drugs that’s available through this program is a good match for the molecular profile of the patient’s tumor and might be a good treatment option. And we intend to include in the protocol some of the criteria that might be used to select a drug to use against a particular mutation site.
“The doctor would then submit the proposed treatment plan to an honest broker — an independent expert group who would review the clinical circumstances of the patient — review the molecular profiling test results, and review the proposed treatment plan offered by the physician to validate that it’s a reasonable approach for this particular patient.
“Once validated, the drug would then be made available to the patient (at no cost to the patient), and the doctor would be obligated to capture the key patient outcomes, both toxicity and efficacy, in the registry.”
2. And the benefits are…
“The basic premise is there are incentives for all the players to participate in a program like this one, which fundamentally provides a vehicle for capturing of good quality, real-world observational data that we can all learn a lot from — that we are not currently able to learn from the off-label prescribing of these drugs.
“Over time we could imagine accumulating lots of data — from hundreds or thousands of patients — on the off-label use of targeted drugs under well-defined circumstances, where we know the characteristics of the patient, the results of the molecular profiling test, the specific treatment that’s been given, and the outcomes for the patient. And then we would share that information broadly with all the participants in the program, and then over time broadly with all of the medical community.
“The patients benefit by having easier access to drugs that they are predicted to benefit from based on molecular profiling test results. The doctors benefit by getting easier access to these treatments. And ultimately the drug companies and the insurance companies benefit by learning a lot about the way in which these drugs are performing in these off-label indications — that information might influence their decision to develop a formal clinical trial, test a promising new lead, or potentially change direction — stop planning for a clinical trial that they were contemplating if it turns out that the real world data does not support it.”
3. What are the next steps to implement a system like this — and potential barriers?
“ASCO will organize the operational aspects of this, which we’re writing a protocol for — and ASCO will ultimately keep the database for the registry. ASCO will also develop all the mechanisms for sharing the data. We’re on a timeline to launch this program early next year.
“I’ve talked to representatives from all the stakeholder groups — doctors, insurance companies, patients, regulatory agencies — and everybody is intrigued by the concept here. Everybody sees its potential value; and essentially all the stakeholders have indicated a willingness to try to work toward making this a reality.
“I would say that the single biggest issue that’s been raised is whether or not the data that would be collected in a project like this is actually of sufficient quality to be useful by all the stakeholders — that this real world observational data can actually enable a regulatory agency or a payer or even a clinical group to make decisions that they have to make — but we won’t know until the data comes in.”
Tuesday, July 08, 2014
With ELIZABETH SMITH, PHD, Professor in Social & Behavioral Sciences in the School of Nursing, University of California, San Francisco
Tobacco use by military personnel is harmful to individuals, it’s harmful to the institution, and there’s no reason to continue supporting or even allowing it — was the argument Elizabeth Smith, PhD, and six co-authors made in a recent Perspective article in the New England Journal of Medicine (DOI: 10.1056/NEJMp1405976).
“People in the military are trying to implement these policies. And it’s really important that they get support from people involved in public health — doctors, nurses, and advocates, including people concerned about cancer,” Smith explained in an interview with OT. Here’s more on why she’s focusing her attention on this issue now…
1. The health risks associated with tobacco are well-known — why is NOW the right time to restrict tobacco use in the military?
“It’s been a good time for a long time. And the military has tried to do a lot of things over the past 20 years, but often Congress has prevented them from implementing strong tobacco control. For example, the Secretary of the Navy Ray Mabus wants to end tobacco sales on navy installations, but the House Armed Services Committee has put an amendment into the defense authorization bill that would prevent him from doing that.
“And that’s where the problem has been for a long time — in Congress, where the tobacco industry has a lot of influence. So public health advocates really need to step up and support the military’s effort to improve the health of the personnel.
“Right now is a good time [to enact this policy] partly because the support from the higher leadership does seem to be there — not only from the Secretary of the Navy, but also from the Secretary of Defense — and also because we’re having a drawdown of our military as forces pull out of combat. Personnel are going to be reduced, so now is a good time to tighten rules and restrict membership.”
2. Is there a precedent to restrict tobacco use in the military? What are the arguments AGAINST restricting its use by the military?
“Yes. Most fire departments do not allow their personnel to smoke because of the health consequences, which is a precedent for restricting tobacco use. It’s never been declared a right.
“It’s never been determined to be a right by any court and smokers are not a protected class. And, many of the rights of military personnel are curtailed in the name of good discipline or good health. Using tobacco is certainly not a benefit — we’re talking about selling members of the military an addictive and deadly product. It’s hard to see how that’s really a benefit, but that argument does get made.”
3. The NEJM Perspective article emphasizes that public health advocates need to support this initiative… Why? What are the implications for larger tobacco-cessation and cancer prevention efforts?
“Having a tobacco-free military sets a great example. It means that for young people who want to join the military, they’re much less likely to start smoking if they know they won’t be able to continue once they join. And once personnel leave the military, we won’t have that pool of people at a higher risk of smoking rejoining civilian life and increasing smoking rates in general. It would be a significant victory.”
Friday, May 23, 2014
With JEFFREY S. WEBER, MD, PHD, of Moffitt Cancer Center
Immunotherapy — particularly for the treatment of melanoma — played a break-out role at last year’s American Society of Clinical Oncology Annual Meeting with pivotal findings for the anti-PD-L1 antibody MPDL3280A and for the ipilimumab-nivolumab combination regimen being reported. Current ASCO President Clifford A. Hudis, MD, deemed it “the beginning of an exciting new chapter of cancer” (OT 6/25/13 issue).
Will the trend continue at this year’s 2014 Annual Meeting?
Yes, said Jeffrey S. Weber, MD, PhD, Director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center — who will be moderating the Oral Abstract Session at ASCO this year on Melanoma and Skin Cancers (Mon., 6/2, 3-6 pm). “But it’s going to have to meet a pretty high bar.”
In an interview, Weber previews what to expect — and what not to miss…
1. Last year was a break-out year for immunotherapy — how will this year top it?
“Last year we saw significant clinical impact with high response rates, long duration of responses, and intimation that you had clearly prolonged survival in patients [with melanoma] who had failed on all other therapies, but then got PD-1 blockade. Everyone realized that these drugs were going to get approved — and it was obvious that they were going to provide significant patient benefit. And it was not just one drug, but three different drugs. Everyone felt the PD-1 blockade had arrived.
“This year, for the first time, we’re going beyond melanoma. You’re going to see some of this in solid tumors. There’s going to be data on the PD-1 antibody in lung cancer. There are studies on tumor infiltrating lymphocytes in cervical cancer and adoptive therapy.”
2. What would you say was the impetus to move immunotherapy beyond melanoma?
“Melanoma is the immunogenic tumor — if an immunotherapy is going to work, you’re going to have to test it in melanoma. But, people realized that when they started to reach across a broad range of cancers in the first Phase I trial of nivolumab, it looked like there was some activity in lung cancer and maybe colon cancer — that was the impetus, and it was a good thing.
“I call it the Rodney Dangerfield effect. His punch line was: ‘I don’t get no respect.’ With immunotherapy, for years people thought it would only work in melanoma, the immunogenic tumor. Now it works really well in melanoma with long survival, and now it’s starting to work in renal cell cancer, non-small cell lung cancer, and maybe other cancers. Now there’s some respect in the field. It’s all about the non-melanoma data.”
3. What about in melanoma — what’s going to be the big immunotherapy news this year?
“You’re going to see expanded data on what came out last year — follow up data and long-term survival data. Antoni Ribas, MD, PhD, will be talking about MK-3475. Michael Atkins, MD, will be talking about pidilizumab, another PD-1 antibody. Stephen Hodi, MD, will be talking about long-term survival for nivolumab. And, Mario Sznol, MD, will be talking about ipilimumab with nivolumab.
“Then you’ll have Howard Kaufman, MD, talking about T-VEC [talimogene laherparepvec], and Alexander Eggermont, MD, PhD, presenting the final definitive Phase III relapse-free survival data from the ipilimumab versus placebo EORTC 18071 trial (the CTL4 antibody).
“Those are all pretty serious.”
Friday, May 16, 2014
With SAMUEL WAXMAN, MD, Founder & CEO of the Samuel Waxman Cancer Research Foundation
NEW YORK — Dozens of cancer researchers convened for two days earlier this week at the Leon and Norma Hess Center for Science and Medicine at Mount Sinai Hospital to discuss the results from their work in brain cancer, blood malignancies, cancer stem cells, lung cancer, breast cancer, and more—and how their findings translate across laboratories and across tumor sites. Their willingness to collaborate is why this group of researchers was chosen to receive funding from the Samuel Waxman Research Foundation.
“To get a grant past the first year, the researchers have to collaborate with other researchers funded,” explained Samuel Waxman, MD, founder and CEO of the Foundation. The idea, he continued, is that including researchers with a diversity of thought offers the best hope of translating progress in cancer treatment across cancer types and research efforts.
That was the lesson of Waxman’s well-known successes in acute promyelocytic leukemia: “That idea is now being translated to other forms of blood malignancies and cancers,” he said.
In an interview at the symposium, Waxman elaborated on the potential of such collaborations.
1. The researchers funded by the Foundation are working on all different types of cancer research — could you explain how that is connected and how the researchers can collaborate?
“We have created a brain trust on understanding what is wrong with the abnormal gene expressions in cancer. It goes across the entire spectrum of cancer. By having that reach, we can understand why a cancer cell doesn’t function properly and what makes it go on to die; why cancer cells have the ability to become resistant to treatment; and why some cancer cells remain dormant but are still able to survive many many years in the patient.
“The Foundation was built on the idea that in order to make progress in curing and finding treatments for cancer, you have to understand what the problem is in the cancer cell. You need really good discovery research. And, that can be done only by highly qualified scientists, and can be done more rapidly by teams collaborating.
“It may be that foundations do better in terms of fundraising if they focus on one kind of cancer — and we discussed this at great length [at the symposium over the past two days]. And, it was the overwhelming opinion of the researchers funded by the foundation that the diversity of thought — having the right brain trust — is what makes this foundation unique.”
2. So how do you select researchers to receive funding and be part of the Foundation?
“We’re looking for real experts — scientists of proven performance. And they have to respond to our mission — that is, to be interested in abnormal function of the gene or pathway that results in cancer cell development — in any form of cancer. We often call this the epigenetic part of cancer control.”
3. Which updates at the symposium were you most excited about?
“There is a form of leukemia that has a problem with a particular gene in the biochemistry of these cells. There is a metabolite building up because of a mutation. But, if you use an inhibitor against it—you can actually get remissions in this form of acute myeloid leukemia (AML). That’s the same idea as what we did in acute promyelocytic leukemia — the cells actually differentiate to stop looking leukemic, they become n-stage leukemic cells, and people go into remission.
“And in colon cancer, there is new research on the effect of diet and inflammation — what particular genes are responding in a way that causes cancer in response to fat, diet, and inflammation, like Crohn’s disease.
“We also heard about some really interesting genes that make proteins that could be drugs, and we heard a lot about cancer stem cells in leukemia and in breast cancer.”
Thursday, May 08, 2014
With ALEC STONE, MA, MPA, Health Policy Director for the Oncology Nursing Society
ANAHEIM, Calif.—The “fixes” to today’s health care (and more specifically cancer care) dilemmas will require more coordination of care, and more individuals to act as navigators to help guide patients through the maze of care regulation, insurance red tape, hospital care, and specialty care — so explained the Oncology Nursing Society’s Health Policy Director, Alec Stone, MA, during a session on health policy issues here at the ONS Annual Congress.
“Almost all successful models of care coordination have incorporated patient-based communication,” he said. “You as nurses — you have the central role here.”
During the session Stone talked about H.R. 1661, legislation that would amend title XVIII of the Social Security Act to provide (paid) comprehensive cancer patient treatment education under the Medicare program. In an interview after the session, Stone reiterated these key points about what the proposed law would change, and how oncology nurses can play a role in getting the bill passed.
1. How would The Improving Cancer Treatment Education Act actually improve cancer treatment education if passed?
“The legislation calls for one hour of one-on-one reimbursed time [$83/hour] to educate cancer patients in an outpatient practice about their symptom management. And that hour of education would be reimbursed by Medicare.
“The idea is that that one hour of education gives the patient an understanding of what their disease is and what the symptoms are, so they can take better care of themselves — and would diminish hospital readmissions — and diminish the need for patients to run to use the emergency room as a primary care physician. An ounce of prevention saves millions of dollars down the road.”
2. And the idea is that once Medicare does it, private insurers will follow suit?
“It’s not immediate — it takes time. But people come to demand it.
“It’s already happening in diabetes. Diabetes educators get $45 for 30 minutes of patient education [reimbursed by Medicare] to teach the patient about how to manage blood sugar levels and how to use insulin, and appropriate nutrition and exercise programs.
“And insurance companies now are not suggesting that diabetics get this education, they are demanding that they get it — because when a patient’s disease is out of whack, it costs more. Now they’re saying it’s much cheaper for us, as the insurance company, to pay the $45 [for that hour of education], than for the patient to come in once a month or once a year [with complications].
”That’s what we’re saying for cancer as well — at the beginning, educate the patient, and later on you don’t have to pay for these other complications.”
3. What’s the next step to get the bill passed?
“Send letters and emails to your elected officials — members of Congress, your representatives and your senators. Educate your legislators. Here’s our bill, 1661. Either, ‘You’re not signed onto it, please sign onto it. I’m an oncology nurse and here’s what I think.’ Or, ‘You are signed onto this. Here’s what I just heard about this. Thank you very much.’
“If a U.S. Representative gets ten emails from ten oncology nurses, someone in that office is going to see that as a red flag. It’s not just one. Ten oncology nurses from one congressional district emailed us. Something is going on. We need to find out what that is.
“Oncology nurses are very powerful advocates and they have very powerful stories — about children with leukemia, about a wife with breast cancer, about a father with colon cancer. These are stories that resonate. They can really move audiences.
“It’s an uphill climb, though. We have 41 bipartisan cosponsors in the House, but we don’t have a companion bill in the Senate. So we’re working to energize our members to reach out to their senators to try to get a bill introduced.”
Get more info on H.R. 1661: www2.ons.org/LAC/WhatONSisDoing/EducationBill or www.govtrack.us/congress/bills/113/hr1661.