PROJECT SUMMARY The overarching goal of this five-year grant proposal, submitted on behalf of the University of Rochester NCI Community Oncology Research Program (UR NCORP) Research Base and the Cancer and Aging Research Group (CARG), in response to RFA-CA-17-052, is: to evaluate whether items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) are associated with tolerability of treatment for advanced cancer in older patients with age-related conditions (i.e., disability, comorbidity, and geriatric syndromes). The growing population of older patients remains underrepresented in research that sets cancer care standards leading to significant disparities in outcomes. In our preliminary research, we found that: 1) close to 60% of older patients develop grade 3-5 toxicity (as measured by NCI's CTCAE) within three months of starting a new treatment regimen; items from geriatric assessment (GA) were significantly associated with toxicity; 2) older patients with advanced cancer frequently experience multiple symptoms that interfere with function and quality of life (QoL); and 3) older patients often experience toxicities that lead to early discontinuation of treatment, hospitalizations, and mortality. We have an unprecedented opportunity to leverage an existing multi-site cluster randomized study that is currently enrolling adults aged >70 years with age-related conditions who are starting a new treatment regimen for advanced cancer in the UR NCORP network (URCC 13059/“GAP”) (n=700). In addition to clinician-rated CTCAE, GAP captures PRO measures (PRO-CTCAE, GA, satisfaction) at baseline, 4 weeks, 3 months, and 6 months after the start of the new treatment regimen. Extensive data are collected on clinical tolerability metrics including treatment dose modifications, hospitalizations, and mortality. We will collaborate with the U01 consortium to: 1) develop and compare the trajectories of PRO-CTCAE scores and clinician-rated CTCAE grades 2-5 in older patients with age-related conditions; 2) evaluate associations between PRO- CTCAE scores and clinician-rated CTCAE grades with clinical tolerability metrics; 3) evaluate associations between PRO-CTCAE scores and clinician-rated CTCAE grades with PRO endpoints (e.g., function, QoL, satisfaction); and 4) validate a model that identifies older patients with age-related conditions who are at high risk for poor tolerability from treatment for advanced cancer. Developed with stakeholders, our operational definition of tolerability is novel; it includes both clinical outcomes and PRO endpoints. The team, which includes expertise in clinical trials (Mohile, Morrow, Janelsins, Kamen), biostatistics and data science (Culakova, Heckler, Pandya, Ramsdale, Zand), PRO measurement (Mohile, Duberstein, Chapman, Flannery), and collaborations with CARG (Hurria, Dale) and patient advocates (SCOREBoard led by Canin) is uniquely suited to conduct this research. This research will address a critical gap in knowledge of how patient-reported toxicity informs tolerability of treatment in older patients with advanced cancer and age-related conditions.

PROJECT NARRATIVE The overarching goal of this U01 grant application entitled “Understanding Treatment Tolerability in Older Patients with Cancer” is to evaluate whether items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) are associated with tolerability of treatment for advanced cancer in older patients with age-related conditions. In collaboration with the University of Rochester NCI Community Oncology Research Program (UR NCORP) Research Base and the Cancer and Aging Research Group (CARG), we have an unprecedented opportunity to leverage an existing multi-site cluster randomized clinical trial that is currently enrolling adults aged >70 who are starting a new treatment regimen for advanced cancer (n=700). In collaboration with the U01 consortium, completion of the aims will stimulate new methods (including methodology for PRO-CTCAE summary scoring and a composite tolerability endpoint that includes both clinical and PRO endpoints) that would guide decision-making and clinical trial design for a growing population of older patients who are traditionally underrepresented in research.