Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer

Background Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy. Methods One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress. Results Primary analyses showed non-significant reductions in weight (−1.1 (−2.4 to +0.2) kg, p = 0.11) and body fat (−1.0 (−2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (−1.4 (−2.5 to −0.2) kg, p = 0.024) and body fat (−1.1 (−2.1 to −0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4–6 of primarily taxane therapy (p = 0.063). Conclusions IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials. Clinical trial registration ISRCTN04156504.

Evaluating the Carg Chemotherapy Toxicity Calculator Among Older Adults Newly Diagnosed with Hematologic Malignancy

Background: Older adults with hematologic malignancy (HM) are a growing demographic and providing effective treatments that balance toxicity and health related quality-of-life (HRQL) is imperative. The well-studied and utilized chemotherapy toxicity tool, the Cancer and Aging Research Group (CARG) chemotherapy toxicity score, has not been validated in hematologic malignancies. Methods: The primary objective of this study was to validate the predictive ability of the CARG score for grade 3-5 toxicity in newly diagnosed (ND) patients >60 years with HM. This was a prospective longitudinal study with 4 study visits: baseline (pre-therapy), visit 2 (Day 90), visit 3 (Day 180), and end-of-study (EOS) which occurred at the earliest of the following events: progression, transplant, or 1-year from baseline. The CARG score was evaluated at baseline. HRQL (PROMIS-GHS) and physical function measured by short physical performance battery (SPPB) were assessed longitudinally at all visits. Treatment toxicity using the NCI CTCAE (version 5.0) were captured monthly, and the worst grade of each type of chemo-related adverse event (AE) was recorded and summarized for each patient. Wilcoxon signed-rank test was used to test if variables changed significantly across visits. Fine and Gray model was used to associate comprehensive geriatric metrics and CARG score with the development of grade 3-5 chemotherapy-related toxicity with death as the competing risk, and Cox model was used to analyze overall survival (OS). Results: Ninety-seven patients with hematologic malignancy (myeloid n=34, lymphoma n=35, plasma cell n=28) were enrolled. The median age was 70 years (range 60-88) with a median 159 days on study (range 1-435). Baseline evaluations: ECOG PS was 0-1 in 69 (85%), median IADL score was 13 (range 5-14), median MOS physical health score was 44.4 (range 0-100), median self-reported KPS was 80% (50-100%), and median comorbidity score was 6 (range 2-12). PROMIS median scores improved from baseline (32, range: 12-49) to EOS (35, range: 16-47, p=0.05). Median SPPB scores improved significantly from baseline (5, range 0-12) to EOS (9, range 0-12, p=0.005). During the study period, 75 patients had 334 grade 1-2 AEs, and 42 patients had 82 grade 3-5 AEs. Hematologic toxicities were more common with 36 (37%) patients having anemia (30 grade 1-2, and 6 grade 3-5) and 11 (11%) patients having febrile neutropenia (all grade 3-5). In multivariable analysis, significant risk factors associated with grade 3-5 toxicity (p<.05) included living alone (HR 3.11, 95%CI: 1.52-6.34) and social activities score (HR 1.21, 95%CI: 1.02-1.42). Risk factors associated with OS in univariable models (p <0.05) were ECOG PS (HR 4.35, 95%CI 2.43-7.79), physical health score (HR 0.86, 95%CI 0.77-0.97), IADL (HR 0.83, 95%CI 0.73-0.95), comorbidities (HR 1.26, 95%CI 1.07-1.48), number of supplements (HR = 0.76, 95% CI 0.60-0.96), memory score (HR 1.08, 95% CI 1.01-1.14), SPPB score (HR 0.87, 95%CI 0.80-0.95) and CARG score (HR 1.12, 95%CI 1.02-1.23). In multivariable analysis, the SPPB score (HR 0.85, 95%CI 0.78-0.93) remained significant for OS. Conclusions: The CARG chemotoxicity score was not predictive of grade 3-5 toxicities in patients ND with HM, but was univariably associated with OS. Higher SPPB scores were strongly associated with OS. Future studies, evaluating modifications of the CARG score are indicated for patients with HM. Objective measures of function, such as the SPPB, may be a reliable method to stratify treatment intensities for older adults with HM. Disclosures Mims: Glycomemetics: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Aptevo: Research Funding; Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Xencor: Research Funding; Kartos Pharmaceuticals: Research Funding; Genentech: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Woyach: AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; Gilead Sciences Inc: Other: Data & Safety; AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee.

Implementing the cancer and aging research group (CARG) tool in the ambulatory oncology setting to drive informed treatment selection.

209 Background: Smilow Cancer Hospital is a NCI designated cancer center in Connecticut that has built a network of 15 community-based oncology (CBO) clinics. Older patients present with unique clinical challenges including multiple comorbidities, decreased functional status, and cognitive impairment. ASCO Geriatric Oncology guidelines recommend completing both a comprehensive geriatric assessment and a chemotherapy toxicity risk assessment on all oncology patients ≥65 years old for informed treatment selection. The CARG calculator is a simple, validated tool to assess chemotherapy toxicity risk in older patients with solid tumors. Despite ASCO guidelines, the existence of validated tools, and literature confirming improved patient outcomes, oncologists’ utilization of risk calculators is limited; therefore, we conducted a pilot CARG quality improvement initiative throughout our CBO network. Methods: 36 CBO physicians agreed to complete five CARG tools, document toxicity scores in the EMR, and complete a post-survey between March and June 2021. PDSA cycles included interventions of a hyperlink to the CARG tool incorporated in the EMR and creating a dot phrase built to simplify documentation. Education was provided on both the CARG and the survey. The survey captured perceived clinical value, time commitment, and barriers to implementation. Baseline data was collected during February 2021 and included geriatric patients receiving a new chemotherapy regimen for a solid tumor. Results: 180 consecutive new chemotherapy starts in geriatric patients were monitored. The CARG score utilization in new chemotherapy starts increased from 6.5% of new cases during the first month, to 26.4% in the third month. 82% of providers found the CARG score helpful in discussing chemotherapy risks with patients. In 32% of cases, the CARG score led to a decision to dose attenuate, and in 15% of cases, the CARG score led to a different treatment regimen. Most oncologists (65%) reported spending ≤5 minutes calculating toxicity, and 88% spent ≤10 minutes. 89% of oncologists reported the CARG score was worth the added time. Conclusions: This QI initiative demonstrates feasibility and increased use of the CARG geriatric chemotherapy toxicity tool in accordance with ASCO geriatric guideline-based care. Physician education and EMR workflow modification were utilized. In the CBO setting, oncologists found the CARG tool to be quick and helpful in discussing treatment risks with patients. Use of the CARG tool led to meaningful changes in treatment, including chemotherapy dose attenuation. Further study metrics such as palliative and supportive care referrals, ED visits, and hospitalizations will fuel sustainability.

Estimating the Risk of Chemotherapy Toxicity in Indian Geriatric Patient Population and Utility of Chemotherapy Risk Assessment Scale for High Age Patients (CRASH) Score

Background Aging is a heterogeneous process, and elderly population is diverse in health status and functional reserve. The present study was undertaken to predict severe chemotherapy toxicity using the Chemotherapy Risk Assessment Scale for High-Age Patients’ (CRASH) score. Materials and Methods Elderly patients (age ≥65 years) with malignancy, who were planned to be treated with a new course of cytotoxic chemotherapy, were enrolled. The CRASH score was calculated, and patients were stratified into four categories, that is, low (0–3), intermediate (Int)-low (4–6), Int-high (7–9), and high (<9). Patients developing grade 3/4/5 nonhematologic (NH) or grade 4/5 hematologic (H) toxicity were taken as the development of severe toxicity. Results Of 100 enrolled patients, 64 (64%) were able to complete their prescribed treatment. Forty-four percent of patients (44 patients) of our study cohort experienced grade-4 H or grade 3/4 NH toxicity. The highest score in each category (heme/nonheme/CRASH) predicts nearly 100% toxicity risk. At a critical value of CRASH ≥ 6.5, the sensitivity is calculated as 100%, while specificity is 89.09%. The accuracy of prediction is 93.88%. The median time taken to develop toxicity was 39.5 days. Conclusion CRASH score utilizes clinical assessment and basic laboratory values. Yet, it accurately predicts severe chemotherapy toxicity above a critical value of 6.5. Based on the above study, the first 30 days are crucial as 45% of patients experienced toxicity in this time frame. With the help of these clinical predictive markers, the care of elderly will be optimized.

Observational study investigating Tolerance Of Anticancer Systemic Therapy In the Elderly (TOASTIE): a protocol

IntroductionThe number of older adults diagnosed with cancer is increasing. Older adults are more likely to have pre-existing frailty, which is associated with greater chemotherapy-related toxicity. Early identification of those at risk of toxicity is important to reduce patient morbidity and mortality. Current chemotherapy toxicity prediction tools including the Cancer and Ageing Research Group (CARG) tool exist but are not in routine clinical use and have not been prospectively validated in a UK population. This study is the first prospective study to investigate the CARG tool in a UK population with cancer.Methods and analysisTolerance Of Anticancer Systemic Therapy In the Elderly is a prospective observational study of patients, aged ≥65 years, commencing first-line (any indication) chemotherapy for a solid-organ malignancy. Patients receiving other systemic anticancer agents or radiotherapy will be excluded. The primary objective will be to validate the ability of the CARG score to predict grade 3+ toxicity in this population. Secondary objectives include describing the feasibility of screening for frailty, as well as the prevalance of frailty in this population and assessing patient and clinician perception of chemotherapy toxicity risk. 500 patients will be recruited over a two year period. Baseline assessments will be recorded. At the end of the 6-month follow-up period, toxicity data will be retrospectively collected. A descriptive analysis of the recruited population will be performed. The validity of the CARG model will be analysed using receiver-operating characteristic curves and calculation of the area under the curve (c-statistic).Ethics and disseminationThe study has received ethical approval from the East of Scotland Research Ethics Service 20/ES/0114. Results will be reported in peer-reviewed scientific journals and disseminated to patient organisations and media.