1. Eastman, Peggy

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Invited speakers at a Congressional briefing on Capitol Hill in Washington, D.C., explored the benefits of immunotherapy drugs and the bright future immunotherapies represent for cancer patients. The briefing was sponsored by the American Association for Cancer Research (AACR) and the Society for Immunotherapy of Cancer (SITC).

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As previously reported in Oncology Times, ASCO named immunotherapy its advance of the year in its annual report for 2017, Clinical Cancer Advances. This was the second year in a row ASCO has named immunotherapy its top clinical advance in treating patients with cancer.


However, the Washington briefing was held at a time of much uncertainty in health care reform. Following the Republican-controlled Senate's procedural vote to move forward in debating a Republican health care reform bill criticized by ASCO and other professional groups (which passed in the House), the Senate's path to repeal and replace the Affordable Care Act (ACA) remains unclear. A new analysis from the nonpartisan Congressional Budget Office (CBO) predicts that repealing the ACA without replacing it could result in 32 million more uninsured Americans by 2020. That analysis also predicts that under repeal premiums on individual health plans would rise 25 percent in 2018 and could double by 2026.


Cancer Care During Health Reform

"Immunotherapies are game changers," said AACR President-Elect Elizabeth M. Jaffee, MD, holder of the Dana and Albert Cubby Broccoli Endowed Chair in Oncology and Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore. She noted that the pace of progress against cancer in the past decade has accelerated markedly, and "the result has been extraordinary." In just the past 6 years, immunotherapies have been approved for 21 indications, added Jaffee, who is an AACR board member and recent Chair of the AACR Cancer Immunology Working Group, and a member of the National Cancer Advisory Board.


Jaffee stressed that, at a transformational time for cancer research, federal funding for the NIH and NCI must remain strong. This federal funding, she said, has turned a corner after many years of being flat, and is the "lifeblood for cancer research." Proposed budget cuts at this time, combined with health reform uncertainty, could have a severe effect on the pace of progress against cancer, she warned.


Asked by Oncology Times in an interview if she is worried about the future effect of health reform and federal budget cuts on cancer patients, she emphasized, "It's a huge issue; I'm very concerned." She stated cuts in funding could have a chilling effect on clinical trials. For example, Jaffee noted that at Hopkins research nurses are paid to help patients enroll in clinical trials, and Medicare is one of the best payers for such trials. Since the risk of cancer rises with age, any cuts in Medicare could result in fewer older patients with cancer enrolling in trials, thus slowing the pace of knowledge derived from trial results.


"Forget about the political issues; there's a domino effect that our politicians don't seem to be aware of," Jaffee said. For example, Johns Hopkins is a huge employer in the state of Maryland, and budget cuts that affect medical research there could result in lower state employment overall and lower economic growth. Jaffee emphasized what is needed now is to "push our politicians to sit down" and examine the ACA to see what is working and what needs improvement.


Individualized Treatment

Based on a new concept in cancer treatment, immunotherapy represents much hope for the individualized treatment of cancer patients, said Steven A. Rosenberg, MD, PhD, Chief of Surgery at the NCI and Professor of Surgery at the Uniformed Services University of Health Sciences and the George Washington University School of Medicine and Health Sciences. Immunotherapy represents a blueprint for the first time because all cancers have mutations, noted Rosenberg, a pioneering immunotherapy researcher who developed effective immunotherapy treatments for patients with advanced cancers. He pointed out that progress in the next few years is likely to be made in identifying rare cells in the body that naturally recognize and fight as foreign the mutations that cause cancer, and then exploiting those cells in the form of cancer-fighting therapy.


Rosenberg cited as good news a recent recommendation by the Oncologic Drugs Advisory Committee to the FDA that the investigational agent tisagenlecleucel be approved for treatment of relapsed or refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia. If approved, this drug would be the first chimeric antigen receptor T-cell (CAR-T) therapy approved by the FDA. The agency does not have to take the advice of its advisory committees, but frequently does. CAR-T cells are genetically reengineered versions of a patient's own immune cells that have been programmed to recognize and destroy cancer cells.


"What we're talking about here is a highly personalized treatment," said Rosenberg. Generally, he said, that kind of individualized one-on-one therapy does not sit well with large pharmaceutical companies, but recently companies have realized that this is a therapeutic approach in which they want to become involved because it can provide cures.


Asked by Oncology Times if an individualized therapy for each cancer patient is economically feasible, Rosenberg said, "The blueprint we're talking about is one drug per patient...It's going to be expensive, very likely." But, he said, the best way to treat cancer is to cure it, and "this is a cure."


In other research, "we found we could produce vaccines that could attach to antigens that are upregulated in cancer cells," stated Lisa H. Butterfield, PhD, President of SITC; Professor of Medicine, Surgery and Immunology; and Director of the Immunologic Monitoring and Cellular Products Laboratory at the University of Pittsburgh Cancer Institute. Involved in four melanoma and three HCC early-stage clinical trials testing vaccines, Butterfield said it is clear that not every patient mounts a strong immune response. So, researchers need to think about how to stimulate immunity in cancer patients with a weaker response. She said she can envision developing cancer vaccines for commonly shared antigens.


Butterfield stressed the importance of grants that involve new investigators at every stage of research on immunotherapies-since they will be the next wave of researchers to achieve breakththroughs in the field. "It is difficult to attract early career scientists into the research lab without knowing that the research center's funding has been secured and is stable," she noted. "Government funding of cancer research must remain strong to incentivize young investigators to remain in the field of cancer immunotherapy research" and enable centers to employ them, she added.


Agreeing with Butterfield was Bernard A. Fox, PhD, Chief of the Laboratory of Molecular and Tumor Immunology at the Robert W. Franz Cancer Research Center within the Earle A. Chiles Research Institute at Providence Portland Medical Center; and a member of the Knight Cancer Institute, Oregon Health and Sciences University. Fox, whose postgraduate training included a stint with Rosenberg at NCI, noted that many science students are not going into academic medicine because of the dearth of funding over the past 10 years.


Like Butterfield and Jaffee, he emphasized the importance of strong federal funding to support the education and training of new investigators who will move the field of immunotherapy forward. "We need to train translational scientists who work closely with clinicians," he noted. Building on research of "cancer-eating" cells, Fox and researchers have developed an enhanced cellular autophagosome, which is able to turn-on a patient's immune system to recognize cancer.


On hand to demonstrate the remarkable benefits of immunotherapy in cancer patients who respond was Stefanie Joho, a cancer research and patient advocate who developed colon cancer at age 22. Joho, a Lynch syndrome patient who did not respond to standard chemotherapy, said she is alive today because of the anti-PD-1 immunotherapy drug pembrolizumab. "I had just graduated from NYU; I had my whole life ahead of me," she told Oncology Times. She is now 27.


Within 3 days of taking pembrolizumab she began to feel better, Joho said at the Washington briefing. "I will not stop fighting until every single patient is as fortunate as I was. We basically all have to step up, because we cannot miss this opportunity."


The FDA has approved pembrolizumab for any resistant metastatic tumor with microsatellite instability (MSI) or other evidence for defective DNA mismatch repair. MSI most often appears in colon cancer; variants of DNA mismatch repair genes are found in Lynch syndrome.


Peggy Eastman is a contributing writer.