Assessment and Intervention May Improve Safety Outcomes in Older Patients Receiving Chemotherapy

In a randomized study, geriatric assessment-driven intervention was effective in reducing chemotherapy-related toxicities in older patients with cancer.

The use of an assessment and intervention strategy to predict high-grade chemotherapy toxicity in older patients with cancer may significantly reduce these toxicities later in the course of treatment, according to a study published in JAMA Oncology.1,2

A large number of patients with cancer in the United States are ≥ 65 years. Investigators of a randomized clinical trial (NCT02517034) sought to determine whether the geriatric assessment-driven intervention (GAIN) was effective in reducing chemotherapy-related toxicities in older patients with cancer.

“Traditionally, oncologists may often use laboratory values and performance status when deciding whether older adult patients are eligible for chemotherapy. However, this may not be enough, and our previous research had demonstrated that by performing an outpatient cancer-specific geriatric assessment, physicians and care teams were able to better detect vulnerabilities and predict chemotherapy-related toxicity among older adults with cancer receiving chemotherapy, which could potentially help with selecting appropriate patients for treatment,” said lead author Daneng Li, MD, assistant professor, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, told Targeted Oncology™ (TO) in an interview.

A total of 605 patients from a National Cancer Institute-designated cancer center who were treated between 2015 and 2019 were enrolled in the study. All patients were at least 65 years of age with a solid neoplasm and were beginning a new chemotherapy regimen and completed the geriatric assessment. Patients in the study were followed until either the end of chemotherapy or 6 months after therapy was initiated.

The geriatric assessment utilized was developed in 2016 at the City of Hope Comprehensive Cancer Center.

“The purpose of creating the cancer-specific geriatric assessment was to provide a more patient-centric form of precision medicine that allows us to detect each patient’s own vulnerabilities, and, thereby, allows us to better effectively care for our older adults with cancer,” stated Li.

Since 2016, the geriatric assessment has been used in multiple studies to identify age-related biomarkers to predict outcomes in patients with cancer, and specifically safety outcomes. Oncologists using the tool have learned a lot about its predictive values since it was first developed.3

“We have learned now for the first time that by incorporating cancer-specific geriatric assessments into the care of older adults with cancer, we can not only detect vulnerabilities that are often not captured with standard oncology assessments, but we also can now intervene on those detected vulnerabilities to have a positive impact on the treatment of older adults with cancer by reducing chemotherapy-related toxicity without compromising survival” Li explained.

Patients were randomized 1:1 to either receive GAIN or standard of care (SOC). Those treated in the GAIN arm had access to an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist who worked together to review their geriatric assessment and perform interventions based on the individual patient characteristics. Treating oncologists were available to those treated with SOC to review the geriatric assessment.1

The purpose of intervening with treatment based on individual disease profiles, according to Li, is because certain factors impact whether or not a patient is fit for chemotherapy.

“Managing chemotherapy-related adverse events [AEs] in older adult patients with cancer can be challenging due to potentially age-associated physiologic decline and multiple comorbidities. Therefore, active interventions as demonstrated in the GAIN study are valuable in attempting to prevent chemotherapy-related adverse events before it occurs,” Li explained.

The incidence of grade 3 to 5 chemotherapy-related toxicity was the primary end point of the study, which investigators determined per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). As secondary end points, the study looked at advance directive completion, emergency department visits, unplanned hospitalizations, the average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. In addition, the study evaluated overall survival (OS) up to month 12 after the start of chemotherapy.

The study population had a median age of 71 years (range, 65-91) and were predominantly women (59.0%). Notably, 22.5% of the cohort had advanced-stage cancer. The most common cancer types among the cohort were gastrointestinal (33.4%), breast (22.5%), lung (16.0%), genitourinary (15.0%), and gynecologic (8.9%). The remaining 4.1% of patients had other malignancies.

Results showed that the incidence of high-grade chemotherapy-related AEs was 50.5% (95% CI, 45.6%-55.4%) in the GAIN arm compared with 60.6% (95% CI, 53.9%-67.3%) in the SOC arm. Therefore, use of GAIN led to a 10.1% reduction in high-grade chemotherapy-related AEs (95% CI, -1.5% to -18.2%; P =02).

Overall, AEs were 13.9% hematologic, 21.2% non-hematologic, and 18.8% hematologic and non-hematologic in nature. The most common hematologic chemotherapy-related AEs observed in the overall population were anemia (18.5%), neutropenia (15.7%), decrease in white blood cells (9.3%), decrease in platelet count (4.3%), and febrile neutropenia (2.5%). Non hematologic chemotherapy-related AEs observed most commonly in the overall study population were infection with normal area under the curve (17.0%), fatigue (8.6%), hyponatremia (6.9%), and nausea, hypokalemia, and dehydration (4.5% each).

There was also an absolute increase in advance directive completion with the GAIN arm versus the SOC arm at 28.4% and 13.3%, respectively (P <.001). But no significant differences were observed between the arm with the number of emergency department visits (P =.41), unplanned hospitalizations (P =.41), the average length of stay (P =.60), unplanned readmissions (P =.85), or chemotherapy dose modifications (P =.30) or discontinuations (P = .08).

In terms of OS, the maximum follow-up time was 10 months after chemotherapy initiation. In total, 204 patients were deceased by the time the analysis was conducted, 24 were lost to follow-up, and 377 were alive. The 6-month probable OS rate in the GAIN arm was 84% versus 83% in the SOC arm. The 12-month estimated OS rate with GAIN was 66% versus 64% in the SOC arm (log-rank P =.55).

“The key takeaway from the GAIN study is that by integrating geriatric assessment-driven intervention into the care of older adults with cancer, we can decrease chemotherapy-related toxicity and hopefully allow older adults to continue to do the things they enjoy in life by tolerating therapy better,” Li concluded.

Li et al recommend that GAIN be used commonly in oncology practice for older adults being treated with chemotherapy.


1. Li D, Sun CL Kim H, et al. Geriatric assessment–driven intervention (GAIN) on chemotherapy-related toxic effects in older adults with cancer. JAMA Oncol. Published online September 30, 2021. doi: 10.1001/jamaoncol.2021.4158

2. Older adults who receive additional supportive care services experience fewer side effects from chemotherapy, City of Hope study finds. News release. City of Hope Comprehensive Cancer Center. September 30, 2021. Accessed October 20, 2021.

3. Geriatric assessment guides treatment strategy for older adults with cancer. News release. City of Hope Comprehensive Cancer Center. December 1, 2017. Accessed October 20, 2021.