Geriatric Assessment-Driven Intervention (GAIN) on Chemotherapy-Related Toxic Effects in Older Adults With Cancer: A Randomized Clinical Trial

Abstract

Importance: Although geriatric assessment-driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown.

Objective: To assess whether specific geriatric assessment-driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer.

Design, setting, and participants: A randomized clinical trial enrolled 613 participants from a National Cancer Institute-designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle.

Interventions: Patients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment's domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration.

Main outcomes and measures: The primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation.

Results: Among the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 [33.4%]), breast (136 [22.5%]), lung (97 [16.0%]), genitourinary (91 [15.0%]), gynecologic (54 [8.9%]), and other (25 [4.1%]). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, -1.5 to -18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P < .001) was observed. No significant differences were observed in emergency department visits, unplanned hospitalizations, average length of stay, unplanned readmissions, chemotherapy dose modifications or discontinuations, or overall survival.

Conclusions and relevance: In this randomized clinical trial, integration of multidisciplinary GAIN significantly reduced grade 3 or higher chemotherapy-related toxic effects in older adults with cancer. Implementation of GAIN into oncology clinical practice should be considered among older adults receiving chemotherapy.

Trial registration: ClinicalTrials.gov Identifier: NCT02517034.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Li reported receiving grants from Brooklyn Immunotherapeutics and AstraZeneca and personal fees from Lexicon, Ipsen, Eisai, Exelixis, Advanced Accelerator Applications, Bayer, Genentech, Taiho, Coherus, Sun Pharma, TerSera, Merck, and QED outside the submitted work. Dr Chung reported research funding from Merck; consulting for Pfizer, Perthera, and AstraZeneca; and participating in speakers bureaus for Ipsen and Coherus outside the submitted work. Dr Fakih reported receiving grants from AstraZeneca, Amgen, Novartis, and Verastem Oncology, honoraria and advisory/consultancy from Amgen, advisory/consultancy from Array, Bayer, Pfizer, and speakers bureaus/expert testimony from Amgen and Guardant 360 outside the submitted work. Dr Chao reported receiving grants and personal fees from Merck and personal fees from Amgen, Macrogenics, Ono Pharmaceuticals, Foundation Medicine, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, and Astellas outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Flow Diagram

GAIN indicates geriatric assessment–driven intervention; SOC, standard of care.

Figure 2.. Geriatric Assessment–Driven Intervention (GAIN) Used in This Study

Under the guidance of the multidisciplinary team and geriatric nurse practitioner, predefined geriatric assessment thresholds were established and interventions recommended. Please refer to eTable 2 in Supplement 2 for a comprehensive list of intervention recommendations. Body mass index is calculated as weight in kilograms divided by height in meters squared.