Our ASCO20 Highlights: From Targeted Drug Study Results to New Strategies for TP53 Testing and More
At the recent American Society of Clinical Oncology (ASCO) Virtual Science meeting, City of Hope presentations ranged in topic and included numerous phase 1 trial results from clinical studies of new therapeutics, oncology patient care approaches and improved testing strategies to help tailor patient treatment plans and improve outcomes.
Find a number of innovative research highlights below.
AMG 510 Shows Anti-tumor Activity in Patients With Colorectal Cancer
Colorectal cancer patients who have a KRASG12C mutation experience poor prognoses due to limited treatment options. Researching the potential of targeted drug therapy to improve outcomes in patients with this type of mutation has been the focus of Marwan G. Fakih, M.D., medical director of Judy & Bernard Briskin Center for Clinical Research and professor in the Department of Medical Oncology & Therapeutics Research.
In a first-in-human, multicenter phase 1 clinical trial of target drug AMG 510, Fakih investigated safety and efficacy by analyzing objective response rate (ORR), disease control rate (DCR), progression-free survival and overall survival in patients with advanced solid KRASG12C tumors. AMG 510 irreversibly inhibits KRASG12C by blocking it in the inactive guanosine diphosphate state.
Four cohorts of patients with advanced colorectal cancer who had experienced progression on standard therapy received different oral dosages of AMG 510. At all dose levels ORR and DCR were 7% (3/42) and 76% (32/42), respectively. At the highest dose level, a similar response was also observed with an ORR of 12% (3/25) and a DCR of 80% (20/25). While the study is still ongoing, the data show that AMG 510 can control colorectal cancer.
An Immunotherapy Approach to Treating Advanced Head and Neck Squamous Cell Carcinoma
At ASCO20, Erminia Massarelli, M.D., Ph.D., M.S., associate clinical professor in the Department of Medical Oncology & Therapeutics Research, presented results from a clinical trial evaluating the safety of inducible T cell co-stimulatory receptor agonist GSK3359609 (GSK609) with platinum+5-FU chemotherapy (5-FU/plat), with or without pembrolizumab (PE), for the treatment of advanced head and neck squamous cell carcinoma.
By combining an immunotherapy drug GSK609 with PE, the current standard of care drug for this type of cancer, T cells are activated directly and indirectly and can mount a larger immune response. In all cohorts, the addition of GSK609 caused no new side effects and didn’t increase previously reported adverse effects of PE or 5-FU/plat.
Massarelli plans on starting a phase 2/3 trial to compare this four-drug regimen to current standard of care treatment.
Geriatric Assessment-driven Interventions Reduce Chemotherapy Side Effects
In order to gain insight on the impact of geriatric assessment-driven intervention (GAIN) on chemotherapy (chemo) toxicity versus standard of care treatment (SOC) in older adults with cancer, Daneng Li, M.D., assistant clinical professor in the Department of Medical Oncology & Therapeutics Research, conducted the first evidence-based randomized controlled study.
Patients enrolled in the study were enrolled in GAIN or SOC arms. In the GAIN cohort, a multidisciplinary team reviewed geriatric assessment results and implemented specific interventions. This type of personalized approach differs from SOC approaches in which a single oncologist guides patient treatment.
Study findings showed a reduction of nearly 10% of chemo-related toxicity in the GAIN arm in comparison to the SOC arm of patients. These findings show the importance of geriatric assessment on patient outcomes. Li and his team are working to expand GAIN to other cancer centers and develop implementation via telemedicine.
Pre-admission Integrated Supportive Care Models Result in Shorter Inpatient Stays
Supportive care services help patients retain quality of life while fighting and living with cancer, but few studies have been conducted to provide quantitative evidence of this. To change this, William Dale, M.D., Ph.D., the Arthur M. Coppola Family Chair in Supportive Care Medicine at City of Hope, and members of the research team, chose to evaluate the impact of pre-admission versus post-admission involvement of an Integrated Supportive Care Model (ICSM) on inpatient length of stay (LOS) using data collected from patients hospitalized at City of Hope.
Data evaluated for patients with hematologic and oncologic malignancies showed a significant reduction in LOS when patients had involvement with the ICSM pre-admission. Shorter hospital stays result in decreased intensive care unit admissions, lowered inpatient costs and increased hospital bed capacity. The team plans on studying how implementing the ICSM in outpatient settings can simultaneously benefit patients and health systems.
A Multi-tissue Strategy for Discerning Acquired and Inherited TP53 Mutations
Inherited germline TP53 mutations, the cause of Li-Fraumeni syndrome, can dramatically increase a person’s risk of developing cancer. Genetic testing to confirm the type of TP53 mutation can be confounded by acquired aberrant clonal expansion TP53 mutations in the blood. Care for Li-Fraumeni syndrome is very different than care needed for patients who develop acquired TP53 mutations and resulting cancers.
Concerned with the lack of discernment and testing resources available for physicians to identify the type of mutation a patient has led Jeffrey Weitzel, M.D., director of the Division of Clinical Cancer Genomics, Dr. Norman & Melinda Payson Professor in Medical Oncology, to develop a multi-tissue testing strategy.
Findings from Weitzel’s study enabled discernment of the status of most TP53 genetic findings, which will allow patients to receive appropriate clinical care and those who don’t have the inherited mutation associated with Li-Fraumeni syndrome to avoid the increased burden of extensive cancer screenings and checkups. Studies continue as part of the Li-Fraumeni and TP53 Understanding and Progress (LiFTUP) project.