Understanding Treatment Tolerability in Older Patients with Cancer - 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.
