A geriatric assessment (GA) intervention to reduce treatment toxicity in older patients with advanced cancer: A University of Rochester Cancer Center NCI community oncology research program cluster randomized clinical trial (CRCT).

Abstract

12009 Background: GA evaluates aging-related domains (e.g., function) known to be associated with cancer treatment toxicity. In this CRCT, we evaluated if providing a GA summary with management recommendations to oncologists can reduce toxicity in older patients (pts) with advanced cancer receiving chemotherapy and/or other agents with a high reported prevalence of grade 3-5 toxicity. Methods: Pts aged > 70 with incurable solid tumors or lymphoma and > 1 impaired GA domain starting a new treatment regimen were enrolled. Community oncology practices were randomized to intervention (oncologists received GA summary/recommendations for impairments) or usual care (none given). The primary outcome was proportion of pts who experienced any grade 3-5 toxicity (CTCAE v.4) within 3 months. Practice staff prospectively captured toxicities; blinded oncology clinicians reviewed medical records to verify. Secondary outcomes included 6 month overall survival (OS) and treatment intensity (standard vs reduced). Outcomes were analyzed using generalized linear mixed/Cox models with Arm as a fixed effect, controlling for practice. Results: From 2013-19, 718 pts were enrolled from 41 practices. Age (mean 77 yrs), sex (43% women), number of impaired GA domains (median 4/8), and treatment type (chemotherapy 88%) were not different by Arm. More pts in intervention were Black (12% vs 3%, p<0.01), had GI cancer (38% vs 31%, p<0.01), and had prior chemotherapy (31% vs 23%, p=0.02). Pts in intervention experienced a lower proportion of grade 3-5 toxicity (175/349; 50%) than pts in usual care (262/369; 71%). The relative risk (RR: intervention vs usual care) of grade 3-5 toxicity was 0.74 (95% CI: 0.63-0.87; p=0.0002); the difference was mostly driven by non-heme toxicities (RR 0.73; 95% CI: 0.53-1.0, p<0.05). OS was not significantly different (71% vs 74%, p=0.3). More pts in intervention received reduced intensity treatment at cycle 1 (49% vs 35%, RR 0.81, p=0.01). Dose modifications due to toxicity were lower in intervention (42% vs 58%, p<0.0001), but results were not significant after controlling for practice (RR 0.85; 95% CI: 0.67-1.08, p=0.2). Conclusions: Providing GA information to oncologists reduces the proportion of older pts who experience grade 3-5 toxicity from high-risk palliative cancer treatment, without compromising OS. Reduced treatment intensity at cycle 1 may explain these results. Funding: R01CA177592, U01CA233167, UG1CA189961. Clinical trial information: NCT02054741 .

ASCO 2020: The Geriatric Assessment Comes of Age

“…Although GA‐guided interventions are effective for improving survival and functional status in several scenarios [2], there is a lack of information regarding the effects of GA‐guided care on traditional “hard” oncological outcomes, such as overall survival (OS), treatment toxicity, or quality of life (QoL) [3]. Fortunately, four randomized clinical trials (RCT) presented at the 2020 ASCO Annual Meeting have provided new evidence showing that the implementation of GA‐guided interventions for older adults with cancer can in fact lead to improvements in QoL and decreased treatment toxicity, without compromising survival (Table 1) [ 4–6]. These RCTs represent a giant leap forward for geriatric oncology, because they provide a strong foundation that will allow for GA‐guided interventions to become the standard of care for all older adults with cancer.…”

“…In the GAP‐70 cluster RCT, investigators from the University of Rochester analyzed the effect of providing GA‐guided recommendations to oncologists working in community practices [4]. Forty‐one practices were randomized to the GA intervention or to usual oncologist‐directed care alone.…”

“…This might be related to the fact that all of the used assessments measure cumulative deficits on broad geriatric domains, which in turn represent a measurement of frailty [10]. An important finding, which was particularly notable in the GAP‐70 trial, was that although patients who received GA‐guided care were less likely to get full‐dose chemotherapy, this did not have a detrimental effect on OS [4]. This mimics the results of disease‐specific chemotherapy RCT in geriatric oncology, such as ESOGIA in non‐small cell lung cancer or GO2 in gastric cancer, which have shown that reduced dosing, or even omission of systemic treatment, may lead to reduced toxicity without compromising survival [11, 12].…”

Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer

“…On the other hand, a recent study indicates that when the GA is not taken into account for prescribing chemotherapy, 34% of unfit patients are overtreated, which is associated with more grade 3-4 toxicity than those receiving treatment adapted to fragility (42% vs. 31%; p < 0.05) (9). In addition, recently, two randomized clinical trials evaluating the impact of GA vs. standard of care on chemo toxicity in older adults with cancer showed the integration of multidisciplinary GA-driven interventions reduced the incidence of grade 3-5 chemo-related toxicity by 10-20% [37,38].…”

Developing an electronic geriatric assessment to improve care of older adults with cancer receiving radiotherapy

“…Until recently, no randomized trial had yet to demonstrate that GA-guided care interventions definitively improve outcomes in older adults with cancer, despite these interventions improving outcomes in older non-cancer populations [45]. However, at the 2020 ASCO virtual meeting, 3 randomized trials were presented and demonstrated GA-based interventions helped improve quality of life and toxicity rates among older adults receiving systemic therapy without decreasing expected survival [27,46,47]. Additionally, to help clinicians better identify frailty, a frailty index (scoring system) generated from the results of GA has been designed that is predictive of all-cause mortality, reduced health-related quality of life, and hospitalizations [48][49][50].…”