BY DEBU TRIPATHY | OCTOBER 8, 2013
Since the HIV epidemic, the Food and Drug Administration has tried several different strategies to bring life-saving drugs to patients more quickly while preserving safety measures. In the cancer world, the need can be just as desperate, but drug development in this area has been hampered by low success rates. This is essentially due to inadequate laboratory models that do not reflect human biology very well and therefore are not very good at predicting what drugs will really make a positive impact cancer treatment. There is no shortage of potential drugs, but the cost required to test them in large clinical trials needed to gain approval forces drug companies to discard most of their drugs and hope they make the right "bet" on which ones move forward.
On Sept. 30, 2013, the FDA approved its first drug using the "neoadjuvant" model, which means drugs are being tested for their ability to shrink early-stage breast cancers prior to surgery. Since the disappearance of invasive cancer correlates with better long-term survival, the FDA proposed this new bar for accelerated approval of drugs as long as subsequent studies confirm their ability to delay or prevent recurrence.
The anti-HER2 antibody Perjeta, had already been approved for advanced HER2-positive breast cancer, when combined with the older antibody Herceptin plus chemotherapy. However, testing it in early-stage breast cancer requires much larger studies and time to determine if it can prevent or delay recurrence. Such studies have begun, but their final results are years away. Following this accelerated approval, Perjeta will now be available for patients with HER2-positive, early-stage breast cancer who are treated with neoadjuvant therapy. Trials are now assessing several new drugs in this fashion, such as the multi-center I-SPY 2 trial, testing a revolving list of targeted drugs with sophisticated tissue and imaging studies to also search for biomarkers that will tell us who will benefit the most.
There are pitfalls, however. Side effects are not as well-known in earlier phases of trials. The relationship between response in breast tumors and survival is quite complicated. The ultimate safeguard is close safety surveillance and parallel studies that look at both response and recurrence. The FDA will revoke drugs that do not eventually show an impact on recurrence, but it makes new drugs available much sooner albeit with less safety data. This is an important milestone in drug development and will significantly cut the time it takes to move drugs in a more curative setting. Hopefully, this is a trend that will be refined over time.
Debu Tripathy, MD Editor-in-Chief, CURE MagazineRELATED POSTS
BY DEBU TRIPATHY | AUGUST 2, 2013
Can a simple act of a few individuals change how we think about cancer?
Well, not a few, anymore, but a growing choir of voices are now redefining the term "cancer." We have known for a long time that there is a continuum from benign to cancerous growth. We even have names for some of these, such as borderline malignancy of the ovary. In the case of ductal carcinoma in situ of the breast (DCIS), the survival of patients is equal to the general population, but it is often treated with surgery, radiation and tamoxifen.
The Institute of Medicine has called for not just a redefinition of names, but a realignment of the cancer culture of "detect and eradicate." A recent article (Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement) in the Journal of the American Medical Association highlights this problem in cancer screening, where the knee-jerk reaction for any cancer is to treat low- and high-risk cancer with many of the same treatment, therefore exposing everyone to side effects and complications while many derive no benefit--because their chance of dying or having their life affect by their "cancer" was minimal.
Solutions proposed in this article include getting rid of the word "cancer" and using terms like "indolent lesions of epithelial origin"--this may alter behavior both on side of the medical team and the patient. Of course, one cannot just declare a new system into existence.
The medical system must provide safeguards that truly dangerous cancers will be diagnosed and treated appropriately. Even some cases of DCIS can recur as invasive cancer, which can then potentially spread and lead to death. This means more research on prognostic tests – a huge ongoing needed in oncology that involves molecular/biological assays and large follow-up studies to validate these tests. We have a long way to go on redefining cancer, but perhaps starting with labeling changes is at least a symbolic start – but hopefully will be followed by both a scientific and cultural shift.RELATED POSTS
BY DEBU TRIPATHY | JULY 15, 2013
I always scan the news headlines before going to work because I don't want to be blindsided by questions from alarmed readers about the latest "association" study published and picked up by the wire and online news services. We are often subject to premature analyses that end up not being verifiable when subject to larger confirmatory studies.
In the case of a recent report showing that omega-3 fatty acid levels are associated with a higher prostate cancer risk, this study did actually confirm early findings of a similar nature. However, I was puzzled by the comments made in the press by the author from Fred Hutchinson Cancer Research Center that men may want to reconsider taking such supplements, or even cut down on omega-3 fatty acid-rich cold water fish consumption.
There is absolutely no evidence of a cause and effect relationship – in fact, very large studies of omega-3 fatty acid intake have not shown effects on cancer risk. Even if there was, we don't know if it is due to enhanced detection due to, for example, effects on PSA levels and this might not have any impact on the risk of prostate cancer spread or death from cancer.
While these studies do set the foundation for more research, the trumpeting of these results to the public without the limitations does create panic and anxiety. How many sleepless nights were experienced on the day of this release by men who believed they were doing the right thing by taking supplements or eating a serving fish two to three times a week?
The scientific and press communities needs to improve their "data quality and interpretation control" systems. This way the public will be able to put the information in perspective, but also will learn how to be a better critic of unfiltered information going forward.
If we do not change things, we run the risk of a fearful public, or even worse, a desensitized and jaded audience who will ignore the next finding that may actually necessitate changes in our lifestyles or new medical recommendations.RELATED POSTS
BY DEBU TRIPATHY | JULY 3, 2013
It may confuse most of us how our DNA, a product of nature that defines our identity and personal traits, could have been patented in the first place. Some claim that patent protection for years of hard work is needed to continue our efforts to isolate and identify genes in order to help develop diagnostic tests and therapies for the good of the general public. [Nature: Myriad ruling causes confusion]
Myriad, the gene diagnostic company that has been in the cross hairs of the recent Supreme Court to invalidate key portions of their patent on the breast and ovarian susceptibility genes BRCA1 and 2, should be credited for their diligent work. They have helped thousands of patients know their cancer risk and act accordingly, and have allowed the medical community to better understand which mutations are actually harmful – something that requires access to large amounts of pooled information.
However, the prices commanded for testing no longer reflect the state of the art of gene sequencing that has dropped precipitously with newer "next generation" sequencing technology. [CURE: Can a Human Gene Be Patented?] Furthermore, the discovery of the BRCA genes were not made in isolation but rather grew out of earlier work to pinpoint the general location of these genes dating back nearly two decades earlier.
Nimble and efficient gene diagnostic companies are popping up like Internet start-up companies of the 1990s. Their day has now arrived as they find new freedom to operate.
The Supreme Court's decision is not fully sweeping and its effects will not be seen overnight [New York Times: Justices, 9-0, Bar Patenting Human Genes]. Larger companies like Myriad still retain significant intellectual property and will probably switch over to offering more complex gene panels tests and tissue assays that go beyond the effect of single gene mutation, but rather the biological impact on tissues. This too, will move the field forward. But will competition in the free market lower prices of testing at the cost of reciprocal stifling of investment and innovation? Only time will tell, but history seems to be on the side of healthy completion equaling continual improvements in both quality and value in most other areas.
We hope the same will pertain to the matter of our genes.RELATED POSTS
BY DEBU TRIPATHY | JUNE 5, 2013
Debu Tripathy, MD, editor-in-chief of CURE, discusses the BOLERO-3 study, which combines the mTOR inhibitor, everolimus, with Herceptin (trastuzumab) and chemotherapy in patients whose cancers progressed on previous treatment. This study was presented at the 2013 American Society of Clinical Oncology's annual meeting in Chicago.
BY DEBU TRIPATHY | JUNE 5, 2013
Debu Tripathy, MD, editor-in-chief of CURE, discusses preliminary studies on combining Herceptin (trastuzumab) with existing drugs to treat HER2-positive breast cancer. These highlighted studies were presented at the 2013 American Society of Clinical Oncology's annual meeting in Chicago.
BY DEBU TRIPATHY | MARCH 8, 2013
A high-profile article was published recently showing a small but statistically significant increase in the rate younger women, aged 25-39 diagnosed with breast cancer with distant metastasis. Published in the Journal of the American Medical Association (JAMA), it's made quite an impact (you can read the full article here). But what are we to make of this, and should anything be done? Should we be alarmed? Well, probably not at this point – it may not even be real.
First of all, this information comes from cancer registry data, which is very good at capturing data at the time of diagnosis, but not long-term follow-up (other than death). So this is really looking at the less common situation of women who actually present with metastases at the time of their original diagnosis – which only happens about 5 to 10 percent of the time, and perhaps more so in women who do not have access to health care and present with higher stage cancers.
Second, the overall numbers are very small – going from 1.53 to 2.21 cases per 100,000 women per year from 1976 to 2009. In the same period of time, there was an also an increase, although small, in this measure for women age 40-54, but not for those age 55 to 84.
Finally, there has not been what would be an expected corresponding disproportional increase in death due to breast cancer reported among younger women over this timeframe, so other causes, such as more aggressive use of CT and PET scans in younger women could account for this - such that the true incidence is not changing, we are just being made aware of it more due to scanning.
Of course, these data do not tell us WHY we might be seeing this increase, or whether we can even verify it. So for the moment we need to look at other information sources and worldwide statistics. We also have to determine if there might be addressable causes, such as limitations of access to care in this population, known as AYA (adolescent and young adult). AYAs do have more barriers to care and other studies have shown that they have not benefited as much with improvements over time in cancer mortality compared with pediatric and older adult populations. More AYAs have no or limited insurance. They are also more mobile and their medical follow-up may be inferior.
While this report should not cause alarm or even affect any of our care guidelines, it may be a wake-up call to truly understand what might be driving this.RELATED POSTS
BY DEBU TRIPATHY | FEBRUARY 18, 2013
Personalized cancer medicine has become a major buzzword as of late, but what does it really mean?
Everyone defines it differently, so the bird's eye view of this term would be as encompassing as possible. On one level, it means that every patient is an individual and that their course through the diagnosis and treatment of cancer should reflect their values and preferences within the boundaries of medical evidence that is works. The way information is communicated, the way different choices are presented, and even how treatment choices are balanced against side effects (sometimes permanent), all need to be customized.
A mother of two young children and a professional violinist might make very different treatment decisions about using a chemotherapy agent that causes neuropathy even if the benefit (improvement in cure rate) is identical. Similarly, the medical care team needs to formulate tailored strategies to keep patients satisfied with treatment, compliant with medications and educated about when to call with side effects. Using a one-size-fits-all approach will probably lead to much lower performance in all these departments.
A very different definition of personalized medicine is the high tech world of genomics and proteomics that exposes unique vulnerabilities in an individual's cancer. Just in the last year, massive amounts of genomic information from the tumors of many patients has been made available through publications and databases-–analyzing this fire hose of data is starting to reveal that cancers do in fact harbor many genetic "drivers," and the next step will be to squelch these with targeted drugs. Also, deciphering inherited variations the drug metabolizing enzymes will help us predict who is more susceptible to drug side effects--further customizing treatments.
The best model of personalized medicine is one that integrates all these definitions to create an environment that revolves around the patient. This includes a rationally composed and individualized treatment plan using the best science along with supportive approaches that add up to a holistic plan that is reflective of the individual. Let's hope that health care reform will encourage and incentivize personalized medicine for cancer.RELATED POSTS
BY DEBU TRIPATHY | JANUARY 24, 2013
Two small steps forward emanated from the ASCO Gastrointestinal Cancers Symposium going on this week, and they both raise the difficult issue of very small gains and what they mean.
In patients with advanced pancreatic cancer, the addition of the chemotherapy agent Abraxane (albumin-bound paclitaxel) to the standard chemotherapy Gemzar (gemcitabine) improved survival by a median of a little under two months. There are no standard therapies for stomach cancer in the second line, and in another study presented, the use of Taxotere (docetaxel) in this setting improved survival by a median of 1.5 months.
What are we to make of these small gains? Are they worthwhile? The answer depends on who you ask, but from my perspective as a medical oncologist, these are truly welcome advances. First of all, we have to recognize that these are average gains, and for a small number of patients the gains could be much longer--maybe exceeding a year. Second, while we recognize that side effects and financial costs have to be reflective of the overall benefit, we also know that these small steps add up, and more importantly lay the foundation for bigger improvements down the line.
We never would have enjoyed the success of drugs like Herceptin for breast cancer or stem cell transplant for leukemia if it were not for the chemotherapy underpinnings that themselves may not be as glamorous or ground-breaking, but are very important components of treatment. However, as we help our patients and families through difficult treatment decisions, we have to be very frank about the projected risks and benefits and must have realistic expectations to temper the hope we all naturally experience.RELATED POSTS
BY DEBU TRIPATHY | DECEMBER 11, 2012
On one of the final days of SABCS there was some interesting updates to Herceptin.
Seven years ago, the original data on Herceptin in early-stage breast cancer was presented. This year, there was an interesting update to the U.S. trial that was presented. That confirmed that Herceptin is saving lives. We now have fewer deaths and fewer recurrences because of this drug. With longer follow-up, the certainty we have with the data is even greater.
Two studies looked at the duration of Herceptin. One study looked at giving Herceptin for two years and another study looked at giving it for less time, for six months. That trial found that results were worse, especially for patients given Herceptin after chemotherapy, which we usually don't do in the U.S. Here in the states, the drugs usually overlap. In that setting, when Herceptin is given for six months, the results were borderline statistically inferior, meaning one year still appears to be a little better than six months. But that's still important because 10 to 15 percent may have to discontinue Herceptin early because of side effects. These results make that decision a little easier knowing that six months of Herceptin still provides some benefit.RELATED POSTS