3 Questions on…
Answers straight from the experts on the latest news and topics in oncology
Sunday, September 27, 2015
With SUPARNA B. WEDAM, MD, Medical Officer at the FDA
SAN FRANCISCO—“We’ve seen kind of an explosion of requests—and I don’t think anybody really expected that,” Suparna B. Wedam, MD, Medical Officer at the U.S. Food and Drug Administration, said about the FDA’s four expedited programs, which she discussed here at the 2015 Breast Cancer Symposium in her talk “FDA Drug Approvals: Getting Drugs to Patients Sooner.” Those four programs include three designations (breakthrough therapy, priority review, and fast track designations) and one approval pathway (accelerated approval).
In an interview after the talk, she summed up these key points and elaborated on what these approval programs mean for the future of oncology drugs.
1. You spent a lot of time during the talk on breakthrough therapy designation, which is the newest program of the four—what should oncologists know about the designation?
“With breakthrough therapy designation, you have to have clinical evidence that this [drug] is substantially better than a significant endpoint, and for fast track designation, non-clinical data can be used. Having said that, we do not accept non-clinical data usually for oncology—typically we require at least some clinical data. Especially in oncology, we feel that [non-clinical] data that comes from cell lines or animals does not always translate well into humans.
“And the other part is the level of senior level involvement. Once a drug has the breakthrough therapy designation, it really is an all-hands-on-board situation from the top down, where the senior manager is helping with the whole process—so, it’s the intensity of involvement that differentiates it.”
2. You mentioned a New York Times article in your talk with the headline “Speedy Drug Approvals Have Become the Rule, Not the Exception”—is that true for oncology drugs? Should these programs be the norm for oncology drugs?
“I think it is true. All of the molecular entities in the last two years that we’ve approved in hematology and oncology, every one of those drugs had taken advantage of at least one of the programs. And many have taken advantage of more than one of those four programs.
“Everything we deal with in oncology is a serious disease [so all of the drugs fit that requirement]. But still, we are approving drugs when we think they’re safe—when we feel the benefit justifies the risk.
3. What are the risks of using these programs?
“There’s caution that needs to be said. We don’t have the same number of patients treated, and we don’t always know that the complete picture that’s not known when we approve a drug. There’s a lot more that we learn post-marketing. And in some of the accelerated approvals we have even a smaller safety base. We need to be very vigilant and follow those safety signals after [the approval] to make sure that this is indeed a safe drug and if there are any safety signals, we need to deal with those.
“And we need to be engaging patients in this process to make sure they understand when a drug was approved through an expedited program. It’s important to explain that the drug was approved in this way and the safety data might not be as complete—and then it’s up to the patient and the physician to make that decision. We [FDA] always feel that it is safe enough to approve the drug—and that’s why it’s out there—but that discussion still needs to happen in the office between the patient and the physician.”
Saturday, September 26, 2015
With experts at the 2015 Breast Cancer Symposium
SAN FRANCISCO—Four oncology thought leaders spoke about ongoing clinical trials in breast cancer and the new directions research needs to go in a session here at the 2015 Breast Cancer Symposium. The trials were too numerous to discuss them all—in the session today or in a single news article—as there are more than 2,400 trials in metastatic breast cancer alone, 131 of which are active, according to www.clinicaltrials.gov, which was noted by speaker Lori J. Goldstein, MD, FASCO, Professor and Director of the Breast Evaluation Center at Fox Chase Cancer Center. Goldstein, who covered clinical trials in systemic therapy for metastatic disease, summed up some of the most notable research in her allotted 18 minutes.
Most exciting though, according to the session’s co-chair Norman Wolmark, MD, Chair of the National Surgical Adjuvant Breast and Bowel Project and Chairman of the Department of Human Oncology at Allegheny General Hospital Cancer Center in Pittsburgh, Pennsylvania, about the current and potentially upcoming clinical trials was the new direction of research, he said in an interview after the session. “We’re seeing a transformation in the way we are perceiving the biology of the disease.
“The clinical trials where we randomized 5,000 patients to answer one question—I think are going to become extinct. We’re seeing targeted therapies with some very exciting results. The results of PALOMA3 for example, with palbociclib; and now putting palbociclib, a CDK 4/6 inhibitor, into the neoadjuvant setting and the adjuvant setting—clearly an example of how things have changed dramatically based on the understanding of the biology of the disease. By the same token, I think we’re seeing the basket trials evolving where we’re targeting a mutation, for example, that might have a 3 percent prevalence.
“Things are moving very rapidly and we’re moving very quickly and we don’t know we’re going to end up, which has always been the challenge, as well as provided the stimulus to move the state of the art forward.”
Basket trials, checkpoint inhibitors, and immunotherapies all come with a lot of questions, Wolmark continued. “And we just don’t know. We really don’t know how to use them properly—in combinations? Sequentially? It’s going to take time, but certainly the environment is a very exciting one.”
The 15 (or so) minutes at the session’s end left for audience questions (asked by the session co-chairs) brought up a few of those unknowns. Here’s what the speakers said.
The session was co-chaired by Wolmark and Kelly Hunt, MD, FACS, Professor in the Department of Surgical Oncology in the Division of Surgery at the University of Texas MD Anderson Cancer Center. The speakers were: Carol Lee, MD, a radiologist specializing in breast cancer at Memorial Sloan Kettering Cancer Center, who spoke about trials in breast imaging; Judy Caroline Boughey, MD, Professor of Surgery at Mayo Clinic, who spoke about trials in locoregional therapy; Debu Tripathy, MD, Professor and Chairman in the Department of Breast Medical Oncology in the Division of Cancer Medicine at MD Anderson, who spoke about trials in systemic therapy for early-stage disease; and Goldstein.
1. WOLMARK asks GOLDSTEIN: “In terms of basket trials—clearly that’s the next horizon and the next challenge—what’s the appropriate control? We saw an example from the Lung-MAP, which took a long time to get started, but now nivolumab’s approved. How does one deal with these challenges?”
“These basket trials are living programs. They have to evolve as the data evolves. They rewrote the [Lung-MAP] study—they changed the study to change the control arm based on the nivolumab data; so we will need to do the same thing.
“One schema I showed was [the investigational] agent plus chemotherapy with chemotherapy as the control. That’s the standard now, but it may not be the standard by the time we open the trial. It may be an Hsp inhibitor; it may be an immunotherapy as a control—depending on where we are at the time of the trial.”
2. WOLMARK asks LEE: “This question was asked—and I shudder to ask because of our commitment to clinical trials—in your heart of hearts, what do you believe the best screening modality to be for women with dense breasts?”
“And perhaps for women in general?”
“Mammography. I say that with no hesitation at all. It’s not perfect, but as I said earlier, it’s the only imaging tool that’s been proven to decrease mortality from breast cancer. So, what we’re doing now in trying to refine and improve on our ability to pick up early breast cancer—that’s all well and good, but we have a tool that’s been proven, and it’s underutilized.”
3. HUNT asks TRIPATHY: “Is triple negative disease really breast cancer?”
“That’s actually a very good question. Yes—triple negative disease is breast cancer, but it has a lot more genetically in common with high-grade serous ovarian cancer, but it is an adenocarcinoma. It expresses cytokines. And as best we know, our paradigms for treatment are similar, with the exception that chemotherapy probably does offer a benefit.
“But we do need to think of these as biologically distinct. So, as an example, the platinum trial that is ongoing is going to see if there is a subset of these patients that may behave differently.
“So, I think the final word on that is still out. There’s basal type; there’s DNA repair deficient; there’s luminal androgen receptor—so it’s really a heterogeneous group of diseases.”
Friday, September 18, 2015
With Jon Retzlaff, MBA, MPA, of AACR’s Office of Science Policy and Government Affairs
Why did 300 doctors, researchers, caregivers, patients, and patient advocates flood Capitol Hill Thursday? Their trek to Washington—for the third annual Rally for Medical Research Hill Day—was to remind Congress that medical research funding needs to be a national priority when it comes to the 2016 federal budget.
“At NIH and NCI, we’ve seen a 25 percent reduction in funding over the past decade (taking inflation into account),” explained Jon Retzlaff, MBA, MPA, Managing Director of the Office of Science Policy and Government Affairs at the American Association for Cancer Research, who was in Washington Thursday. “You’re talking about going from one in three grants that were being funded back in 2003 to about one in six today. That’s leaving a lot of great ideas on the cutting room floor.
“The goal of our effort is to inspire the support of Congress to provide the National Institutes of Health with robust, sustained, predictable budget increases for the 2016 fiscal year.”
AACR was the founding organizer of the first rally that took place in 2013, which included 10,000 people representing 205 organizations (OT 5/25/13)—and AACR has continued to play a key role in organizing the event. In between Thursday’s events on Capitol Hill, Retzlaff answered these questions in a phone interview about how the situation has changed since the first rally—and what still needs to change.
1. What has changed since this effort began in 2013—in terms of the message, the participants, and the response?
“The message is starting to get traction. There’s a convergence of support for medical research that we really haven’t seen in many many years. And there are all kinds of reasons for that. The medical research community has been doing a great job of educating and informing members of Congress as to why NIH needs to be a national priority; and I think we’ve really gotten to a point collectively where the messaging battle is understood and, to some degree, has been won. Members of Congress really are talking about NIH needing robust, predictable, and sustained budget increases—and it needing to be a national priority.
“We had four influential Senators speak last night [at the Rally for Medical Research evening reception] in support of this effort: Senator Patty Murray (D-WA), Ranking Member on the Subcommittee on Labor, Health, and Human Services within the Appropriations Committee; Senator Dick Durbin (D-IL), number two in the Senate in the leadership; Senator Amy Klobuchar (D-MN), who actually requested to speak this year—she said this was one of the most important causes out there; and Senator Jerry Moran (R-KS), a member on the Subcommittee on Labor, Health, and Human Services with the Appropriations Committee. And this morning we heard from House Chairman Tom Cole (R-OK) [at a breakfast to kick off the rally’s Hill Day], who showed immense leadership this year. He proposed a $1.1 billion increase for NIH.
“Now I think the message has really resonated. And we are on Capitol Hill today to push to get over the finish line in terms of having these increases provided.”
2. What’s the finish line? Despite the changed momentum, what challenges still need to be overcome to actually get more NIH funding?
“We have to have these budget caps raised; and we have to have sequestration eliminated at some point. It’s a macro-economics issue right now. Without those changes, there’s no room—even though there’s the interest—to provide those increases. There are not enough resources available to provide NIH with these necessary increases unless we do that.”
3. So what’s actually happening in Congress today for Hill Day?
“We have 300 individuals going to Capitol Hill to advocate on behalf of NIH. Those 300 individuals all have schedules. We will be meeting with 80 Senators (40 states are represented). And they will be meeting with more than 200 Representatives in the House. We’re going to be blanketing Capitol Hill today with information, with passion, with stories of hope, and with stories of success about why NIH funding needs to be a national priority.
“Our advocates here in D.C. today are survivors, advocates, family members, representatives of the supporting organizations, doctors, researchers, and young investigators. That’s really been the value—having every sector really represented here and participating in this—the entire medical research eco-system.
“I think anyone on Capitol Hill today—if they don’t know what the rally medical research is going into today, they’ll know what it is after being on Capitol Hill today.”
Friday, September 11, 2015
With GUILHEM BOUSQUET, MD, PHD, of Hôpital Avicenne in Bobigny, France
What’s the best way to break bad news to a patient? It depends on the patient, the patient’s family, the news, the prognosis, where the conversation is taking place—and when—and numerous other factors, said Guilhem Bousquet, MD, PhD, Associate Professor in Medical Oncology and researcher in the Medical Oncology Unit at Hôpital Avicenne in Bobigny, France. “The oncologist needs to constantly adapt to each patient and each situation.”
Though various medical communities have developed recommendations to improve the communication skills of health care professionals in delivering bad news—oncologists and oncology care providers included—there is still a dearth of data on the experience of doing so, Bousquet and his colleagues explain in a metasynthesis report recently published in the Journal of Clinical Oncology (2015;33:2437-2443). Their research systematically reviewed 40 qualitative studies that focused on the experiences and points of view of oncologists about breaking bad news to patients to determine common themes, as well as where research was lacking.
In an email interview, Bousquet told OT more about the work.
1. What was the impetus for this review—and why did you choose a metasynthesis?
“Most research in this area has focused on the patient’s point of view—which is important—but as a medical oncologist, I wanted to address the question of the oncologist’s perspective about breaking bad news.
“We did a metasynthesis—a systematic review of qualitative studies, which is more suitable for investigating health-care issues in context because it takes into account interactions, behavior, and perceptions within groups and teams. The metasynthesis methodology makes it possible to synthesize numerous small qualitative studies that are contextually specific and interesting, but have little generalizability. It identifies the themes from each of the individual studies, compares these themes across all of the selected studies, and constructs broad categories formed by the themes that are sufficiently supported, frequent, and pertinent.
“Our metasynthesis provides the first overview of oncologists’ experiences regarding breaking bad news, and it enabled us to build generalizable theories that provide a deeper and more textured understanding than could be obtained from quantitative research alone.”
2. What did you learn?
“Oncologists need to constantly adapt to each patient and each situation when it comes to delivering bad news. And we learned that the repeated emotional experience of breaking bad news is invasive, complex, and inevitable. And when it comes to breaking bad news, the emotional capacity of the oncologist in his or her daily practice needs to be taken into account.
“More educational programs are needed. Oncologists should be offered specific training in listening. And education should include training on the ‘external factors’ that shape the patient-oncologist encounter—particularly the family and cultural factors.
“And oncologists should be taught coping strategies they can use to deal with their own feelings and emotions. Regardless of the programs and/or efforts to improve their communications skills, providers need to be taught that the emotional experience they live will remain extremely complex, invasive, and hard to manage over time.”
3. And in what areas did you find that more research is still needed?
“There is a lack of research in the cultural factors that can strongly affect the experience of both giving and receiving bad news. Each culture structures the representations that individuals have about death and disease differently. Physicians and patients interact in a particular cultural context that shapes their respective ways of dealing with the question of death—and potentially with the best way to receive and/or give bad news.
“So what do we do when the physician and the patient come from different cultures? Do we talk about death directly? Is death associated with religious practices that structure the transition between life and death? What is the place of the family?
“The physician must take the patient’s perspective into account. Very little is known about the burden of breaking of bad news for oncologists in a context of multi-ethnic diversity.”
Monday, August 31, 2015
With CHARLES FUCHS, MD, MPH, of Dana-Farber Cancer Institute and Harvard Medical School
Another win for java in the should-you/shouldn’t-you debate. New data showed that patients with colon cancer who drank four or more cups of coffee a day were less likely to have their cancers recur or to die compared with patients with colon cancer who did not regularly drink coffee, according to a study now published online ahead of print (JCO 2015 doi: 10.1200/JCO.2015.61.5062).
Previous studies have shown that diet and lifestyle do influence an individual’s risk for developing colon cancer, said the study’s corresponding author Charles Fuchs, MD, MPH, Director of the Gastrointestinal Cancer Center and Institute Physician at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. “But it’s a bit of an inference to conclude that those studies necessarily inform how patients with colon cancer would do with any particular diet modification.
“So we decided to prospectively look at diet and lifestyle, and as it relates to cancer risk, get the same data for a population of patients being treated for cancer to see which diet and lifestyle choices might influence the ultimate outcome from their cancer.”
And as Fuchs and his colleagues hypothesized, similar to how coffee has been shown to play a role in colon cancer risk, it also appears to play a role in outcomes for patients who have been diagnosed with colon cancer.
The researchers analyzed data from a cohort of 953 patients with stage III colon cancer from the National Cancer Institute-sponsored Cancer and Leukemia Group B 89803 for which patients prospectively completed food frequency questionnaires four months after surgery (at which point they were receiving chemotherapy) and six months after completion of chemotherapy. Compared to patients who drank no coffee, patients who reported consuming four cups or more of caffeinated coffee per day had a 45 percent reduction in risk for cancer recurrence and a 46 percent reduction in risk of death from any cause. The researchers adjusted risk for sugar-sweetened beverage intake and glycemic load, which their previous work had showed also play a role in outcomes for patients with colon cancer.
The researchers also compared the effects of caffeinated coffee versus decaffeinated coffee and found that when analyzing decaffeinated coffee consumption alone, there was no link to improved outcomes. While those findings might mean that caffeinated coffee yields a benefit in terms of colon cancer outcomes that decaffeinated coffee does not have—it also might be the case that the low number of decaffeinated coffee drinkers in the study was inadequate to statistically show a benefit.
The bottom line, Fuchs said: “Patients who were regular caffeinated coffee drinkers had a significant improvement in their outcomes—namely a lower risk of cancer recurrence and a better survival.”
Why? Here’s what he told OT in a phone interview.
1. You said it was an “inference” that the diet and lifestyle choices that influence colon cancer risk would also influence colon cancer outcomes—why did you suspect there might be a connection?
“CALGB 89803 started in order to collect dietary information in this population of stage III colon cancer patients. We found over time that a number of factors do influence outcomes for these patients—namely that patients who are obese and who are sedentary do worse, and patients who avoid exercise and exercise regularly have better outcomes. And in this cohort of patients [for which coffee consumption was followed], we also found that consumption of sugar sweetened beverages was associated with worse outcomes; and having a high glycemic load diet was associated with worse outcomes.
“Many of these factors seemed to be risk factors for the development of type 2 diabetes—obesity, sedentary lifestyle, high glycemic load diet, high consumption of sugar sweetened beverages. And what’s curious is that other research has shown that people who have a history of type 2 diabetes actually do worse from colon cancer. So we wanted to look and see whether factors that influence diabetes risk could influence outcomes for patients with colon cancer.
“And coffee has—relatively consistently—been a factor associated with lowering the glycemic risk of type 2 diabetes—so that was the motivation to look at coffee consumption.”
2. So what is the mechanism for coffee having this protective effect?
“We suspect that given that we’re now consistently finding the risk factors for diabetes having a similar modifying risk on outcomes for these patients with colon cancer, we are at least hypothesizing that the ability of coffee to improve outcomes may be through that pathway.
“At a mechanistic level how is it doing that? We don’t know yet. What component of coffee might be contributing to the benefit? We don’t know. And what pathway is it influencing in colon cancer that might improve outcomes?
“I think those are very important questions. Not only does it give you better insight into the nature of the causality, but it also gives you potential clues toward better treatments. We believe that these pathways—referred to as energy-balance pathways or the pathways that relate to diabetes and glucose metabolism—are relevant. And if we understand what the target of these ‘interventions’ (in this case coffee) is in the cancer cells, then potentially we could even come up with a more sophisticated and targeted approach that might benefit these patients even more beyond these lifestyle habits.”
3. So, based on these findings, what is the message to practicing oncologists about whether or not patients with colon cancer should drink coffee?
“The findings do require confirmation. This is one study—it has a fair number of patients and it’s prospective in its design—in that we collected the information on diet and lifestyle before we knew anything about the individual outcomes for patients. But you want to see a confirmatory study; and we are in the process of planning that.
“Right now for patients who have been recently diagnosed with colon cancer and they enjoy coffee—I would say, don’t stop drinking it. This study suggests there may be a genuine benefit. If someone says, I hate the stuff, I would say, then don’t drink it.
“As it is stated in the paper, regular exercise, avoiding obesity, avoiding a high glycemic load diet, avoiding sugar-sweetened beverages, and avoiding an excessive Western diet all also seem to contribute to a meaningful benefit. So I wouldn’t tell somebody to start drinking coffee if that’s not something they’re inclined to do.”