On Saturday, the curtain rose on one of the nation’s premier cancer events, the American Association for Cancer Research (AACR) Annual Meeting 2015, which runs through April 22 in Philadelphia. The AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research.
Two encouraging Memorial Sloan Kettering studies were featured in the meeting’s press program, which highlights research deemed significant and deserving of media attention by an AACR panel of experts. Also, exciting new results regarding an immune-based cancer therapy were presented from a study co-led by a MSK physician-scientist — and reported the same day in the New England Journal of Medicine.
In addition, several of our investigators were honored or assumed leadership roles at the meeting — notably MSK Physician-in-Chief José Baselga who officially began his one-year term as AACR President.
Targeting Epstein-Barr Virus to Treat a Lethal Transplant Complication
Richard O’Reilly, Chair of the Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplant Service, reported positive news from two clinical trials testing a novel way to treat a devastating complication associated with stem cell transplants. The approach, led by Dr. O’Reilly and MSK pediatric oncologist Susan Prockop, uses virus-targeted T cells (a type of immune cell) to wipe out lymphoma cells transformed by Epstein-Barr virus (EBV) in the transplant patient.
EBV is present in most people but usually produces only mild symptoms because the immune system keeps it in check. However, transplant patients often have weakened immune function, allowing EBV to awaken and induce infected cells to divide uncontrollably as a cancer in the lymph nodes, spleen, liver, lungs, or brain.
The trials involved giving patients immune cells called cytotoxic T cells (CTLs) that had either been isolated from the transplant donor or selected from a bank of cells generated from other donors with normal immune function. The CTLs were collected and exposed to EBV to stimulate them to fight the virus. The CTLs that recognized EBV were expanded in the laboratory and stored in a bank. T cells selected from the bank and infused into a patient attacked the cancerous cells transformed by EBV and destroyed them.
In these trials, the EBV-CTL treatment was given to patients whose EBV had not responded to the drug rituximab (Rituxan®), the standard treatment for EBV lymphoma following a stem-cell transplant. The clinical trials showed that the therapy put more than 60 percent of these patients — who otherwise would have a median survival of less than 2 months — into long-lasting remissions with no significant side effects.
The trials showed that the EBV-CTL therapy is effective whether the T cells used are from the patient’s transplant donor or from the bank of T cells contributed by healthy third-party donors.
Based on this success, the US Food & Drug Administration in March granted MSK Breakthrough Therapy Designation — intended to speed the process of approval — to develop EBV-CTLs from third parties. MSK is working with Atara Biotherapeutics, Inc. to continue refining and expanding the technology.Back to top
Drug Blocks Hormones Fueling Breast Cancer Growth
Medical oncologist Maura Dickler reported results from an early-stage clinical trial suggesting that a new drug for breast cancer is safe, enabling this research to move forward into the next phase testing its effectiveness. The drug, GDC-0810, could benefit patients who have become resistant to current therapies or whose breast cancer has returned.
Most breast cancers are estrogen receptor (ER)-positive, which means the tumor cells carry estrogen receptors on their surface. These receptors allow the cancer to be fueled by the hormone estrogen. Patients with this breast cancer type usually receive therapies — such as aromatase inhibitors and tamoxifen — that either lower estrogen levels or occupy the estrogen receptors to prevent the hormone from stimulating the cancer cells. However, these hormonal therapies often stop working and the cancer returns.
GCD-0810 not only occupies estrogen receptors, it also degrades them, leaving them temporarily inactive. This effect could provide an advantage over current treatments in slowing the growth and survival of ER-expressing cancer cells.
The clinical trial tested GDC-0810 in women with ER-positive breast cancer that had returned or continued growing after standard hormonal therapy. PET imaging using a fluorescent estradiol agent revealed that the drug occupies the estrogen receptors efficiently and prevents estrogen from being taken up by the cancer cells.
In addition, the findings suggest the drug might be effective against tumors that have developed resistance to standard hormone therapy due to mutated estrogen receptors. Side effects of the drug were manageable.
“Resistance to hormone therapy is a major problem for women with metastatic, ER-positive breast cancers, and new treatments are urgently needed.” Dr. Dickler says. “Therapies such as GDC-0810 that are effective against these treatment-resistant tumors could be a significant advance for these patients.”Back to top
Combination Immunotherapy Works Better than Single Drug for Melanoma
A study co-led by MSK medical oncologist and immunologist Jedd Wolchok, medical oncologist Michael Postow, and F. Stephen Hodi, an immunologist at the Dana-Farber Cancer Institute, showed promising results using a two-drug combination to treat melanoma. As reported in the New England Journal of Medicine (NEJM), the use of two immunotherapy drugs, ipilimumab (Yervoy™) plus nivolumab (Opdivo™), produced significantly better outcomes than ipilimumab alone in patients with advanced melanoma.
Dr. Hodi presented findings from a clinical trial testing the two-drug combination in 142 patients with metastatic melanoma who were previously untreated. The response rate — based on tumor shrinkage — was significantly higher in the patients receiving the combination therapy (61 percent) compared with patients receiving ipilimumab plus a placebo (11 percent). The effect of the combination therapy also proved more durable, as patients receiving both drugs lived longer without their disease progressing. Side effects of the combination therapy were manageable.
The response rate — based on tumor shrinkage — was significantly higher in the patients receiving the combination therapy.
Metastatic melanoma is the deadliest form of skin cancer, and until recently treatment options were very limited. Dr. Wolchok, Chief of the Melanoma Service, and other MSK researchers played a major role in developing ipilimumab and nivolumab. Both drugs remove a natural brake on the immune system, using slightly different mechanisms.
“We are excited about these results and believe they support the principle that rationally combining effective medicines is an approach to achieving better outcomes for patients,” Dr. Wolchok says.
NEJM also had a brief report from Dr. Wolchok, along with MSK medical oncologists Paul Chapman and Sandra D’Angelo, describing the remarkable effect of the ipilimumab-nivolumab combination in one patient whose whose melanoma had returned several years after surgery. The woman had a large tumor under her breast, but a single treatment with the two drugs caused the entire mass to disappear in only three weeks.
Several Memorial Sloan Kettering investigators were honored at the meeting:
- MSK Physician-in-Chief José Baselga was officially inaugurated as AACR President and began serving his one-year term. He will work with the AACR Board of Directors and membership to further the association’s mission to prevent and cure cancer through research, education, communication, and collaboration. Dr. Baselga assumed this post just a year after Charles Sawyers, Chair of Memorial Sloan Kettering’s Human Oncology and Pathogenesis Program, completed his term as AACR President in April 2014.
- MSK President and CEO Craig Thompson was formally inducted as a Fellow in the AACR Academy. Each year, the existing Fellows select for induction a group of 11 new scientists “whose major scientific contributions have propelled significant innovation and progress against cancer.”
- Jedd Wolchok was named co-leader of a new $20 million Dream Team focusing on lung cancer, supported jointly by Stand Up to Cancer and the American Cancer Society. Over the three-year life of the grant, the Dream Team will focus on ways to target lung cancers with mutations in the KRAS gene, which account for 20 to 25 percent of lung cancer patients. “We will combine targeted drug therapies with immunotherapy,” Dr. Wolchok said.
Charles Sawyers and Howard Scher, Chief of the Genitourinary Oncology Service, received an AACR Team Science Award together with Michael E. Jung, a professor at UCLA. The three researchers were named to the Designing AR Inhibitors Team for their collaboration in discovering a targeted therapy for metastatic castration-resistant prostate cancer.