University of Cincinnati Cancer Center researchers will present abstracts at the American Society of Clinical Oncology Annual Meeting May 30 to June 3 in Chicago.
Study details baseline characteristics of AYA survivors seen in oncology primary care clinic
Cancer rates in adolescent and young adult (AYA) patients diagnosed between the ages of 18 and 39 have increased in the last decade. Due to their young age at diagnosis and potential to live decades beyond treatment, AYA survivors are at a higher risk for secondary primary malignancies and other comorbidities compared to older cancer survivors.
The Cancer Center’s Alique Topalian, PhD, and colleagues examined the baseline characteristics of AYA patients seen in the Cancer Center’s oncology primary care clinic, one of the only clinics of its kind in the country, using data from a clinical registry designed to measure longitudinal outcomes.
“We believe that oncology primary care providers are uniquely positioned to address the increased needs the AYA population may face across the lifespan,” said Topalian, research scientist in the Department of Family and Community Medicine’s Division of Survivorship and Supportive Services in UC’s College of Medicine.
The team found approximately 10% of the clinic’s population was diagnosed as AYA. Among AYA patients, 14% were diagnosed with a second primary malignancy and 60% had a cardiovascular disease such as hypertension. Neurologic, endocrine and psychological comorbidities were also common.
More than half of the patients were overweight/obese, with 19% being former smokers and 7% being current smokers. Many eligible patients received recommended screenings for breast (82%), colon (60%) or cervical (40%) cancer.
With this baseline of data, Topalian said next steps include longitudinal monitoring of AYA patients in the clinic to monitor changes in health outcomes and comparing the population to survivors seen in general primary care settings.
“There is still so much to learn about our early onset cancer survivors and complications they may face as they age, making comprehensive primary care services and longitudinal monitoring imperative in this high-risk population,” she said. “Tailored education and outreach efforts for providers and patients should address preventative health services needed in this high-risk population.”
As the work continues, Topalian said she is excited to see more of a focus on this area of research. The National Cancer Institute’s Interdisciplinary Network for Survivorship and Primary Care Research and Education initiative has a current focus on oncology primary care, and ASCO created a separate submission category for AYA cancer research for this year’s annual meeting.
“Previous presentations on this population would be grouped in with pediatric or adult sessions. As a cancer survivor diagnosed as an AYA, I am happy to see our professional organizations taking this important step in raising awareness and encouraging research to improve the health outcomes of this population,” Topalian said. “The face of cancer is changing, and people are living longer post-diagnosis than ever before, so our research and interventions must change with it.”
Topalian will present “Oncology primary care clinics for comprehensive care of high-risk adolescent and young adult (AYA) cancer survivors” June 1 from 9 a.m. to 12 p.m. Other coauthors include Melinda Butsch Kovacic, Elizabeth A. Shaughnessy and Melissa Erickson.
Study specifies overexpression of protein in AML
Previous research has found a hyperactive version of a protein called IRAK4L to be overexpressed in acute myeloid leukemia (AML) cells, but it was not known exactly how overexpressed the protein is.
The Cancer Center’s Eric Vick, MD, PhD, and colleagues examined the levels of IRAK4L in animal models and patient-derived cell lines and tested the effect of chemotherapy drug azacitidine and targeted therapy drug venetoclax on the cancer’s IRAK4L expression.
“Almost all of our samples showed some amount of IRAK4L, which is expected, but most AML cell lines expressed almost exclusively IRAK4L,” said Vick, instructor in the Division of Hematology/Oncology in UC’s College of Medicine and an attending physician at the Cancer Center’s Blood Cancer Healing Center. “Treatment with azacitidine and venetoclax transiently decreased expression, but it returned to pretreatment levels after recovery of those samples.”
Vick said research is ongoing to develop drugs that inhibit the IRAK4 protein as part of a larger approach to better treat AML, and some formulations are likely to be ready for clinical trials later this year.
“This combination should help prevent AML from ‘escaping’ treatment,” he said. “We’re looking into several ways to translate this and other targets of immune activation as potential targets in AML, and how to treat our patients more effectively.”
Vick will present the poster “The IRAK4 long isoform as widely upregulated in non-spliceosome mutated acute myeloid leukemia and as altered by hypomethylating agent therapy” June 1 from 9 a.m. to 12 p.m. Other coauthors include Sean Walulik, Avery Sampson, Aishlin Hassan, Mark Wunderlich, Andrew Volk and Daniel Starczynowski. The research was supported by the generosity of patients donating samples and funding through the Leukemia & Lymphoma Society, ASCO, Cincinnati Children’s Hospital and UC.
Oncolytic virus found to be safe as trial continues
Oncolytic viruses, a form of immunotherapy, are specially engineered viruses used to infect and destroy cancer cells. The Phase 2 IGNYTE trial is testing RP1, a genetically modified herpes simplex type 1 virus designed to directly destroy tumors and generate anti-tumor response.
The Cancer Center’s Trisha Wise-Draper, MD, PhD, and colleagues conducted a biosafety analysis among patients with skin cancer who have been enrolled in the trial so far.
“We reviewed the safety and replication of virus outside of the tumor, as the virus should only replicate inside the tumor to kill the tumor cells,” said Wise-Draper, professor of medicine in the Division of Hematology/Oncology, section head of medical oncology, co-leader of the Head and Neck Experimental Advancement Laboratory in UC's College of Medicine, and deputy director of UC's Office of Clinical Research.
The researchers found very little virus detected in the blood, in the urine or on the surface, and there were no reports of family members or contacts becoming infected.
“Essentially, the virus was doing what it should and was safe,” Wise-Draper said. “The trial will continue, but we can feel better about no active virus that could be contagious to others.”
Wise-Draper will present the poster “Biosafety analysis from the skin cancer cohorts in the IGNYTE trial of RP1” June 1 from 9 a.m. to 12 p.m. Other coauthors include Caroline Robert, Michael K. Wong, Joseph J. Sacco, Gino K. In, Eva Muñoz Couselo, Dirk Schadendorf, Georgia Beasley, Jiaxin Niu, Bartosz Chmielowski, Mohammed M. Milhem, Tawnya L. Bowles, Katy K. Tsai, Celeste Lebbe, Caroline Gaudy-Marqueste, Junhong Zhu, Jeannie W. Hou, Robert S. Coffin, Aaron Clack and Praveen Bommareddy.
Trial tests drug effectiveness to treat rare head and neck cancer
Adenoid cystic carcinoma (ACC) is a rare type of head and neck cancer with no standard systemic treatment. When ACC spreads to other organs, treatment is difficult, and patients face poor outcomes.
Current medications used to treat ACC are not well tolerated and the cancer tends to develop resistance, highlighting the need for new treatment options.
Under the mentorship of Wise-Draper, Olga Zamulko, MD, and colleagues conducted a Phase 2 clinical trial testing a new medication called amivantamab that has been found to overcome treatment resistance in lung cancer but had not been studied in ACC.
“We asked if amivantamab would overcome this resistance mechanism in ACC and lead to improved responses and tolerable side effects,” said Zamulko, an internal medicine resident in the College of Medicine.
The trial enrolled 21 patients with amivantamab, with one patient reporting a partial response measured as a 30% tumor decrease and 10 patients reporting stable disease. Patients reported minor side effects, including rash and infusion reactions that were easily managed, and did not report decreased quality of life while on the treatment.
“The clinical benefit rate was 61%, indicating that amivantamab may be a potential treatment in patients who previously failed many different kinds of therapies with limited available options,” Zamulko said.
Moving forward, the team is examining each patient’s tumor to look for genetic or cell-specific biomarkers that could be a target for future treatment options.
“Then we will decide if we should enroll more patients and expand this study or if we should look for new treatment combinations with amivantamab,” Zamulko said.
Zamulko will present the poster “Amivantamab for recurrent/metastatic adenoid cystic carcinoma: A multicenter, single-arm, phase 2 clinical trial” June 2 from 9 a.m. to 12 p.m. Other coauthors include Wise-Draper, Glenn J. Hanna, Douglas Adkins, Jianmin Pan, Audrey Romano, Maria Lehn, Allison Forsythe, Casey L. Allen, Kathryn A. Wikenheiser-Brokamp, Christopher Lemmon, Dalia El-Gamal and Shesh Rai.
New treatment offers hope for young patients facing an aggressive kidney cancer
Translocation renal cell carcinoma (tRCC) is a rare but fast-moving kidney cancer that strikes children and young adults far more often than it does older adults. Fusion or extra copies of the TFE3 or TFEB genes lead to its growth, and until now no drug has been proven as a treatment when the disease spreads.
Cincinnati Children’s Hospital’s James I. Geller, MD, will share results from the national Phase 2 AREN1721 trial at the conference. The study tested whether pairing two existing medicines — nivolumab, which boosts the immune system, and axitinib, which cuts off a tumor’s blood supply — can slow tRCC better than either drug on its own.
The trial enrolled 13 eligible patients between the ages of 7 and 42 from 2019 to 2023. Six received the drug pair, two received axitinib alone, and five received nivolumab alone. Even with such small numbers, tumors in the combination group took a median of 10.5 months to start growing again, compared with just 1.8 months for patients on nivolumab by itself.
Overall survival was also longer for the combination arm, and about one-third of those patients saw their tumors shrink at least partly — an effect not seen with single-drug nivolumab therapy, which by itself was inactive.
Side effects were in line with what doctors already know about each medicine, and no unexpected safety problems appeared.
“That treatment can hold this cancer in check for many months and is an important step forward and good news for families facing tRCC; however, further advances are needed,” said Geller, the study’s overall chair and lead investigator at Cincinnati Children’s and a Cancer Center member.
“A Randomized Phase 2 Trial of Axitinib + Nivolumab Combination Therapy vs. Single-Agent Nivolumab for the Treatment of TFE/Translocation Renal Cell Carcinoma (tRCC)” was led by the Children’s Oncology Group within the National Cancer Institute’s Clinical Trials Network. Geller will present the trial results during the Genitourinary Cancer—Kidney and Bladder moderated panel discussion May 31 at 1:45 p.m.
Other coauthors include Nicholas Cost, Lindsay A. Renfro, Matthew R. Zibelman, Ana M. Molina, Mamta Parikh, Luke E. Pater, Ian Tfirn, Elizabeth A. Mullen, Peter F. Ehrlich, Elisabeth T. Tracy, John A. Kalapurakal and Jeffrey Dome.