Julie Brahmer

Julie Brahmer, M.D., is interviewed at the ASCO 2016 meeting.

Julie Brahmer, M.D., director of the Thoracic Oncology Program, began treating patients with immunotherapy drugs nearly a decade ago. She led one of the first large studies of the popular drugs, which was reported in 2012. Since then, Brahmer has become an expert in identifying and managing side effects that come with taking the drugs. “Patients can experience side effects that include anything that ends in –itis,” says Brahmer. They are typically ones that involve inflammation, such as colitis (inflammation of the colon) and the worst of them, pneumonitis (inflammation of the lungs). These types of side effects aren’t unexpected, says Brahmer, when taking medicines that tinker with the immune system, and inflammation is considered an immune-related biochemical process. Aside from inflammation-related side effects, fatigue often tops the list of the drugs’ side effects, says Brahmer. She says some patients also experience low thyroid hormone levels. A new study of patients receiving immunotherapy at the Kimmel Cancer Center may reveal a connection between the drugs and the development of inflammatory arthritis.

“Patients are concerned about drugs’ side effects,” says Brahmer. “So, we need to educate clinicians and learn to recognize and treat side effects early.” The toxic effects of the drugs can occur anytime during a patient’s regimen, she says, even after patients stop taking the drugs. If side effects occur, they are typically at low grade levels, but some have more severe effects. Treatment includes oral corticosteroids, and, for severe problems, hospitalizations may be necessary.

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Dr. Tom Smith at #ASCO16.

Dr. Tom Smith at #ASCO16.

Tom Smith, M.D., wants cancer patients to live well. Fewer side effects, better quality of life, more joyful time with family…these are among the primary goals, he says, of palliative medicine. Researchers have studied the impact of palliative medicine programs on patients’ outcomes, and results show that patients benefit, says Smith. “A lot of aggressive chemotherapy is given in the last six months of life, and only about 18 percent of these patients ever use hospice, so they are missing an important part of good cancer care.” says Smith, director of Palliative Medicine at Johns Hopkins Medicine and the Harry J. Duffey Family Professor of Palliative Care at the Johns Hopkins Kimmel Cancer Center. Professional organizations, including the American Society of Clinical Oncology (ASCO), have pointed to better treatment outcomes among patients who have six months or less to live and are in hospice programs. “They have better quality of life, better caregiver support and at least two studies have shown that cancer patients who use hospice live longer than those who don’t. There are multiple studies that show cancer patients who get palliative care alongside their usual care have better quality of life, fewer symptoms, can plan better, and live longer, too,” says Smith, who discussed an #ASCO16 presentation  by researchers at the University of North Carolina, Chapel Hill.

So, how can more patients access palliative medicine programs? Smith says the concept of palliative medicine should be introduced early in cancer care -- for every patient -- through consultations with palliative medicine teams, apart from the primary oncologist. Smith suggests GetPalliativeCare.org for more information and PrepareForyourCare.org for tips on how to manage serious illness. He also says that doctors should encourage the concept of “prognostic awareness” sooner than later with their patients, by having specific and honest discussions about prognosis throughout their care.

Watch Smith discuss end of life care in this MedPage Today video and read his comments on the American Association for Cancer Research blog.

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Suzanne Topalian

Immunotherapy expert, Suzanne Topalian, M.D., delivered a presentation to a standing room only crowd at the 2016 American Society of Clinical Oncology (#ASCO16) regarding new directions in scientists’ search for biomarkers that identify patients and tumor types most likely to respond to immunotherapy drugs. Among the approaches is an immunohistochemistry test for the protein PD-L1, which is found on the surface of cancer cells. PD-L1 binds with its partner, PD-1, a protein found on immune cells, to create a chemical “handshake” that blocks the immune system from identifying and killing cancer cells. Several immunotherapy drugs against PD-1 or PD-L1, called “immune checkpoint blockers,” aim to disrupt this chemical connection. A chemical test performed on biopsy specimens identifies patients whose tumor cells are studded with the PD-L1 protein and may be more likely to respond to checkpoint blocking drugs.  However, there are still many patients whose tumor test for the PD-L1 protein are negative and can respond to the drugs. “This is a complex biomarker,” said Topalian, associate director for the Bloomberg-Kimmel Institute for Cancer Immunotherapy. “There are different interpretations and scoring of the commercially available tests and other tests in development, and more study is needed.”

Another response-predicting biomarker targets mutations in DNA mismatch repair genes found in cancer cells. The connection between the mismatch repair gene mutations and response to the immunotherapy drug pembrolizumab (anti-PD-1) was first described at last year’s ASCO meeting. From that research, scientists at the Kimmel Cancer Center showed that patients whose tumors have these mutations (about 10-15 percent of colorectal cancers and 2-4 percent of other cancer types) are more likely to respond to pembrolizumab. Topalian said last year’s data are holding up and tumor responses occur in about 50 percent or more of patients with these mutations.

Finally, scientists have some of the first evidence, based on data presented earlier this year by Topalian and colleagues at the Fred Hutchinson Cancer Research Center, that patients who have virus-linked skin cancer called Merkel cell carcinoma may also respond well to receiving the immunotherapy drug pembrolizumab (anti-PD-1) as their first therapy. Additional data presented by Howard Kaufman from Rutgers at #ASCO16, showed that among 88 patients with this rare but aggressive form of skin cancer, 32 percent of them had significant tumor regressions after receiving an immunotherapy drug called avelumab (anti-PD-L1), and most of the responses were ongoing at the point of the data’s analysis. Patients who had had two or more previous therapies did not respond as well as those who had only one round of chemotherapy. Taking this and the previous study into context, Topalian noted that these two immunotherapy drugs target the same pathway and seem to mediate regressions in advanced Merkel cell cancers. She said there may be more of an advantage in using these drugs in the first line of therapy for these cancers, however, more observation of patients and additional studies will be needed to provide evidence. For Merkel cell carcinoma, a rare cancer that is classified as an orphan disease, Topalian added, “these two national and global studies highlight the importance of networking centers.”

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With recent FDA approvals of immunotherapy drugs for kidney and bladder cancer, patients now have more options to consider among their treatments. The 2016 ASCO annual meeting featured several new developments in these two cancers that seem to keep the momentum moving forward in this field. We asked Charles Drake, M.D., Ph.D., associate director of the Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins, to discuss the significance of the findings.

Following the recent FDA approval of an immunotherapy drug called atezolizumab, which targets a molecule called PD-L1, for second-line treatment of advanced bladder cancer, scientists revealed data from another clinical trial of the drug: Results from a phase II study investigating the PD-L1 inhibitor atezolizumab as first-line therapy for patients with advanced bladder cancer who cannot safely undergo standard therapy (Abstract LBA4500).  In the trial, atezolizumab was given to bladder patients who were not healthy enough to receive conventional high-dose chemotherapy. So, the patients in the trial were given atezolizumab as a so-called first-line therapy. He said, “The response rate in these patients was actually quite good – in the range of about 25 percent.” It’s important, he says, because it gives a good option for these patients. In addition, he says immunologists have long questioned whether checkpoint blockade drugs would work as a first-line treatment as effectively as second or third-line treatments. Moving forward, he says the findings are important for providing bladder cancer patients who are medically ineligible for conventional chemotherapy a new treatment option with a good response rate. With additional clinical trials, Drake’s hope is that scientists will find a “chemo-free” regimen for bladder cancer patients. David McConkey, Ph.D., director of the Johns Hopkins Greenberg Bladder Cancer Institute, also commented on the FDA's approval of "atezo" for second-line treatment of bladder cancer. Watch Drake's video commentary.

Also at #ASCO16, kidney cancer experts will be presenting long-term follow up data on the effectiveness of the immunotherapy drug nivolumab as second-line treatment for kidney cancer patients. Long-term overall survival (OS) with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies.

Drake, a co-author on the study, says that the data shows favorable outcomes for these patients, specifically that there is a one in three chance that a patient taking this drug in the second line of treatment will be alive 2, 3 and 4 years from now. The scientists also looked at the rate of adverse events over time and whether patients develop long term, autoimmunity-related side effects (which includes arthritis, colitis or pneumonitis). Drake says that the findings are encouraging that there was no indication of long-term autoimmunity-related side effects. He says most of the side effects occur within the first three to six months. Watch Drake's video commentary.

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David McConkey

David McConkey, Ph.D.

A new immunotherapy drug -- the first in its class -- was approved by the Food and Drug Administration last week for bladder cancer. We asked David McConkey, Ph.D., director of the Johns Hopkins Greenberg Bladder Cancer Institute, to explain the significance of this milestone:

"The approval of atezolizumab is arguably the most transformative thing that has happened in our field since the development of cisplatin-based combination chemotherapy over three decades ago.  (In fact, the transformation actually started with the first high profile reports of major clinical activity almost two years ago.)   We had no targeted agents and nothing meaningful to offer patients who had progressed after cisplatin-based therapy.   Investigators and their industrial partners are now developing and/or performing trials with these agents in every disease state.  An important question is whether combinations of atezolizumab and other immune-active agents will produce even greater clinical activity. There is also a pressing need to develop better biomarker-based clinical tools to identify the patients who will obtain the most benefit from these drugs.

The recognition that atezolizumab and other immune checkpoint inhibitors are clinically active has also had a strong beneficial side-effect by rekindling industrial interest in developing other targeted agents in bladder cancer.  For example, we are seeing renewed interest in developing FGFR inhibitors for patients whose tumors contain activating FGFR3 mutations.  These mutations are found in a significant fraction of muscle-invasive cancers (15-20%) and the majority (almost 80%) of non-muscle invasive cancers.  Importantly, the published data from the Phase II atezolizumab trial (Rosenberg et al, Lancet 2016) suggested that the patients whose tumors belonged to the subset of tumors that is enriched with these mutations (“papillary,” TCGA cluster I)  also obtained the least benefit from immune checkpoint blockade.  Therefore, FGFR inhibitors could prove to be active in patients whose tumors are resistant to atezolizumab.  There are a lot of other attractive candidate biological targets in bladder cancers, so hopefully this interest in checkpoint blockade will translate into a strong interest in developing better therapies for bladder cancer overall."

Stay tuned for more developments in bladder cancer. Watch a patient education seminar.

What do you think of this new drug approval?

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This past weekend, the Avon Foundation held its 14th annual event in Washington, D.C. to raise funds for breast cancer research and education. More than 1,900 participants from 41 states and Washington, D.C. walked 39.3 miles in the AVON 39 The Walk to End Breast Cancer. Of the total $4.8 million raised during the weekend event, the Johns Hopkins Kimmel Cancer Center was awarded $750,000 for research, patient navigation and a retreat for metastatic breast cancer patients. Kimmel Cancer Center scientist Sara Sukumar, Ph.D., won a $300,000 grant to study a gene called HOXA5, which acts as a tumor suppressor in normal breast cells. She'll study what goes awry in the gene to lift the brakes on tumor suppression, making breast cells turn cancerous. Josh Lauring, M.D., Ph.D., and Sukumar, who are members of the Breast Cancer Program, accepted the awards at the event. Were you at the event? Tell us your story.

Breast Cancer Program members Josh Lauring and Sara Sukumar accept Avon Foundation awards

Breast Cancer Program members Josh Lauring and Sara Sukumar accept Avon Foundation awards

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In today's lineup of stories covered by WNYC's radio program The Takeaway, Kimmel Cancer Center expert Josh Lauring, M.D., Ph.D., provides his perspective on a new study published yesterday in the journal Nature by the Wellcome Trust Sanger Institute. The study is an analysis of the genomic sequencing of 560 breast cancer patients. Listen to Lauring and radio host John Hockenberry discuss the study:

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At the 2016 American Association for Cancer Research annual meeting today, scientists presented their results of a follow-up study tracking the survival of metastatic melanoma patients who were treated with the immunotherapy drug nivolumab. The drug is currently approved by the U.S. Food and Drug Administration for advanced lung and kidney cancers and advanced melanomas.

Results published in 2014, by a group led by Suzanne Topalian, M.D. professor at the Johns Hopkins Kimmel Cancer Center and associate director for the Bloomberg~Kimmel Institute for Cancer Immunotherapy, showed the first hints that nivolumab could produce lasting, increased survival among patients with metastatic melanoma.

Today’s presentation, also co-authored by Topalian, shows an overall survival rate of 34 percent after four and five years among 107 patients with advanced melanoma who were treated with nivolumab. Typically, the relative five-year survival rate of patients with metastatic melanoma is approximately 16 percent.  In other research, long-term survival rates of metastatic melanoma patients who received another type of immunotherapy drug, called ipilimumab, were reported as approximately 21 percent.

Nivolumab aims not to kill cancer cells directly, but to block a pathway that shields tumor cells from immune system components that are potentially able and poised to fight cancer. The pathway includes two proteins called programmed death-1 (PD-1), expressed on the surface of immune cells, and programmed death ligand-1 (PD-L1), expressed on cancer cells. When PD-1 and PD-L1 join together, they form a biochemical shield protecting tumor cells from being destroyed by the immune system.

“This is the longest follow up for any anti-PD-1/PD-L1 trial,” says Topalian. “We’re encouraged by the long-term survival data.  Our next steps are to find ways to combine immunotherapy with other treatments to push survival rates even higher, and continue studying the biology of tumors to learn why certain patients with cancer respond to immunotherapy and others do not.”

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Kristin Franchesci

Kristin Franceschi competes in a ballroom dancing event.

***Note: This is the final post of a four-part feature story, written by Elizabeth Huebeck. Read part one on Kristin's story, part two on cancer as a chronic disease and part three on Kristin's strategies for staying the course.

Regardless of which treatment path cancer patients take, painful and uncomfortable side effects cannot be avoided. How well therapies are tolerated often depends largely on patients’ overall health before and while battling cancer.

“My pulmonary function is more robust now than before my third lung surgery,” said Kristin. She attributes this improvement to lifting weights after her surgery, a strategy suggested by a member of her healthcare team to ensure optimal strength of her chest wall.

That’s just one way Kristin has made her health a priority during her cancer journey. In addition, she has relied on yoga for rehab after all three of her lung surgeries. She ardently watches her diet. And she has adopted meditative practices, which she says have been incredibly helpful during stressful times, like when she’s waiting on the table to get a scan, sitting in the waiting room, or about to go into surgery.

All these suggestions point to the same mantra that has helped see Kristin through the last five years: “The healthier you are, the better you’re going to be able to survive,” she said.

Kristin says that, right now, she feels great. But she also knows that at any point in the future, she may learn from a CT scan that her cancer has re-emerged. “You just have to take one day at a time. Put one foot in front of the other,” she says. Fitting advice from a ballroom dancer.

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***Note: This is the third of a four-part feature story, written by Elizabeth Huebeck. Read part one on Kristin's story and part two on cancer as a chronic disease.

Kristin Franceschi

Kristin Franceschi 

Accepting primary control of your disease

As a patient, Kristin Franceschi has learned that sometimes, after receiving the best standard practices of standard care, the cancer may return or metastasize and additional treatment may still be required. And for these next steps, a clear linear treatment path doesn’t always exist. Sometimes, that may mean choosing between less-than-perfect options—each of which can pose potentially risky side effects.

Kristin recalls some of the tougher treatment decisions she’s had to make during her cancer odyssey. “I have had to consider that I could die on the operating table if I undergo surgery. But if I do the [clinical] trial first and wait on the surgery, the tumor could grow,” she shared.

While a patient’s medical team can and should weigh in on these decisions, ultimately, acknowledges Kristin, it’s the patient who must choose. She refers to this ownership as “playing quarterback” throughout the disease process, and it’s something she urges other patients to do.

“As a patient, you have to look at every trial. I spent a huge amount of time trying to figure out what trials were possible for me,” Kristin recalled.

While playing quarterback or taking control of your cancer can mean being the ultimate decision maker for significant medical decisions—like which cancer trials might be right for you and which treatments you should receive in what order—it can also mean finding ways to manage seemingly smaller, albeit significant, issues.

For instance, as a side effect of chemotherapy treatments, Kristin suffered from a severe skin reaction on her face and neck that caused painful burning and inflammation. After a lot of trial and error, she developed a skin regimen that was part coconut oil, part a bee venom lotion, and part Bert’s Bees. Relieved to find something that cleared up the problem significantly, Kristin happily shares her “finding” with other patients who experience similar skin reactions.

Seek expert second opinions

Although Kristin urges patients to take control of their disease, she acknowledges that seeking input from trusted medical professionals is critical to making informed decisions about treatment options.

“I would engage in the conversation about going to Hopkins, even if your diagnosis is routine. I tell other patients: Do yourself a favor and get a second opinion,” Kristin said.

In an academic medical setting such as Johns Hopkins, patients benefit from the clinician-scientist model of pioneering and practicing best standard practices. Institutions such as Johns Hopkins also tend to have much more experience than smaller, community hospitals treating rare and aggressive cancers.

Stay tuned for the final part of the series on how Kristin monitors her health. Subscribe to this blog.

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