ASCO chooses CAR T-cell immunotherapy as its top clinical advance of 2018. The FDA approved this adoptive cell immunotherapy in 2017 to treat adults with diffuse large B-cell lymphoma, as well as children and young adults with acute lymphoblastic leukemia. CAR T-cell immunotherapy genetically reprograms patients' white blood cells to unleash their bodies' immune defense against cancer. It is being studied to fight other types of cancer, notably multiple myeloma.
ASCO's top advance appears in its new report, Clinical Cancer Advances 2018, which is done annually (J Clin Oncol 2018; doi:https://doi.org/10.1200/JCO.2017.77.0446).
ASCO named immunotherapy as its top overall clinical advance for the years 2016 and 2017. This year's report includes a new statistical analysis of clinical trial data from the ASCO Center for Research and Analytics showing that 250,000 years of life could be saved for U.S. patients with advanced non-small cell lung cancer for whom currently approved checkpoint-inhibiting immunotherapies are indicated and who receive these drugs.
Hope in Precision Medicine
The new ASCO report was released 1 day before ASCO held the conference “Precision Medicine: Expanding Opportunities” at the National Press Club in Washington, D.C. At this event, ASCO CEO Clifford A. Hudis, MD, FACP, FASCO, noted that the bright promise of precision medicine—of which immunotherapy is a prime example—has been only “minimally exploited so far.” Also, he said, not every U.S. cancer patient who could benefit from precision medicine is receiving it.
Noting that CAR T-cell immunotherapy took many years to develop and received federal support, Hudis stressed that federal funding for cancer research is critically important. The new ASCO report notes that more than 25 percent of the top advances featured on its pages were supported by the NIH and other federal agencies. The report states that federal funding has led to the following:
- a 25 percent decline in the cancer death rate (since a peak in 1991);
- 110 new cancer drugs or drug indications approved by the FDA since 2006; increased 5-year survival; and
- 15.5 million cancer survivors alive today.
“I'm glad to have lived long enough to see this,” said ASCO President Bruce E. Johnson, MD, FASCO, Chief Clinical Research Officer and Institute Physician at the Dana-Farber Cancer Institute, and Professor of Medicine at Harvard Medical School, Boston. His theme as ASCO President is “Delivering discoveries: expanding the reach of precision medicine.” He said his personal interest is making sure everyone who receives a cancer diagnosis has access to precision medicine, which includes targeted therapies as well as immunotherapies.
In addressing the question of “whether the hope is worth the hype” for precision medicine, Johnson answered in the affirmative. He said subsets of cancer patients are currently being defined by who can be treated successfully with precision medicine.
As a specific example, “I've seen a dramatic change in how we treat patients with lung cancer,” noted Johnson, who is currently Interim Director of the Center for Cancer Precision Medicine at Dana-Farber. Since 2015, the FDA has approved three immune checkpoint inhibitors for lung cancer: nivolumab, pembrolizumab, and atezolizumab.
Non-Hodgkin follicular lymphoma survivor Judy Wilkins of Salem, Mass., one of the first patients treated on a clinical trial with CAR T-cell immunotherapy, said she was initially skeptical about entering a clinical trial when her oncologist recommended it. Wilkins, who has owned a local hair salon for more than 30 years, was concerned about potential side effects from the immunotherapy clinical trial, but now her attitude has completely changed because of her positive experience. Diagnosed in November 2013, she underwent chemotherapy. She had her T-cell transplant in August 2016, and 6 weeks later her scans showed no signs of cancer. She is active and working. “If you're in a position to go into a clinical trial, do it,” she said. “Life is good; I'm very lucky.”
While immunotherapies have been a boon to many cancer patients, they have brought some side-effect management challenges to clinicians, especially those in the community. Asked by Oncology Times to address these challenges, Suzanne L. Topalian, MD, Associate Director of the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, noted that immunotherapies are “quite new,” and scientists want to develop biomarkers to identify cancer patients who might be more susceptible to side effects from these drugs.
In her experience, she explained that most of the side effects are manageable, but “oncologists do need to become more educated on how to use these drugs.” She noted this is especially important for cancer patients with comorbid conditions, and suggested that a cancer patient with chronic obstructive pulmonary disease, for example, might be best served receiving immunotherapy in a tertiary care center.
A key challenge right now is to empower physicians in less-populated areas to implement the level of precision medicine for cancer patients that is expected today, said Edward S. Kim, MD, Chair of Solid Tumor Oncology and Investigational Therapeutics, Medical Director of the Clinical Trials Office, and the Donald S. Kim Distinguished Chair for Cancer Research at the Levine Cancer Institute, Carolinas HealthCare System, Charlotte, N.C.
Kim praised ASCO's Targeted Agent and Profiling Utilization Registry (TAPUR) study, a real-world clinical trial to empower physicians to understand the efficacy and safety of FDA-approved, targeted anti-cancer drugs for patients whose advanced cancer has a genomic variant targeted by a TAPUR study drug. The overall objective of the study is to learn about new uses for these drugs outside of their approved indications.
“The elegance of a trial like TAPUR is in its practical nature,” said Kim. TAPUR aims to collect data on clinical outcomes for the following:
- help find additional uses for approved drugs;
- help physicians learn from real-world prescribing patterns;
- educate oncologists about how to use genomically targeted drugs;
- catalogue oncologists' choice of genomic profiling tests; and
- provide new knowledge about the use of registry data to generate hypotheses for additional clinical trials.
Precision medicine depends on accurate genomic tests, and speakers at the ASCO conference stressed the importance of tests oncologists can trust. About 3-4 emails a week come in from companies wanting to sell her their genomic test, said Barbara L. McAneny, MD, CEO of New Mexico Oncology Hematology Consultants, President-Elect of the American Medical Association, President of the New Mexico Medical Society and Founder/Chair of the Board of the National Cancer Care Alliance. “I'm seeing a patient every 15 minutes all day long,” said McAneny, so she has little time to spend researching every test.
While genomic testing is easier and faster now, the proliferation of tests requires due diligence, which is helped by the use of professional guidelines, said Anna B. Berry, MD, Scientific Director of the Personalized Medicine Program at the Swedish Cancer Institute and Director of Molecular Diagnostics at CellNetix Pathology and Laboratories. She advises physicians to say to vendors of genomic tests, “Show me your validation data.”
In addition to CAR T-cell immunotherapy, some other highlights from the new ASCO report on clinical advances include the following.
- In May 2017, the FDA set what the report terms “a milestone” in the history of precision medicine by approving the first tissue-agnostic treatment, pembrolizumab. This drug was approved for adults or children with advanced solid tumors (regardless of their location) that harbor the genetic changes of mismatch repair deficiency or high microsatellite instability.
- New targeted regimens of the PARP inhibitor olaparib were shown for the first time to lower the risk of cancer progression in women with advanced BRCA-related breast cancer. While PARP inhibitors are FDA-approved for ovarian cancer, new evidence also demonstrates clinical benefit for women in this subset of breast cancer patients.
- In 2017, the FDA approved olaparib as a new maintenance therapy for women with recurrent ovarian cancer who responded to platinum-based chemotherapy.
- The new report states that about 50 percent of U.S. cancer cases and deaths could be prevented if people pursued healthy lifestyles. In the area of cancer prevention, for example, the report notes that evidence now shows that using e-cigarettes is a strong risk factor for smoking, which could lead to a spike in smoking prevalence in the long-term. The FDA began regulating e-cigarettes, smokeless tobacco, and water pipes on Aug. 8, 2016. ASCO's Cancer.Net provides information on the risks of e-cigarettes and smokeless tobacco.
- Also in the area of cancer prevention, the ASCO report states that 5-6 percent of new cancer cases and deaths globally are directly linked to drinking alcohol. But 70 percent of Americans do not recognize alcohol as a risk factor for cancer, according to a 2017 ASCO opinion survey. The report states, “Oncologists are uniquely positioned to identify strategies to help their patients reduce alcohol use; address racial, ethnic, gender, and sexual orientation disparities that may place these populations at increased risk of cancer; and serve as community advisors and leaders to raise awareness of alcohol as a cancer risk behavior.”
- Looking to the future, the report cites promising research on a new class of drugs, stapled peptides, which target protein-protein interactions. Stapled peptides, which are now in clinical trials, have a shape-holding artificial chemical bridge (staple) that allows them to penetrate cells. The ASCO report notes that, although “targeted therapies have had a profound effect on cancer medicine, only about 20 percent of proteins in cancer cells can be targeted by currently available medicines.”
Peggy Eastman is a contributing writer.