Treatment modifications, like dose reductions, schedule changes, or less toxic regimens, can improve how older patients with advanced cancer and ageing-related conditions tolerate chemotherapy regimens, suggest researchers.
Older patients, they said, are under-represented in clinical trials, and reported risks associated with standard-of-care regimens typically reflect outcomes in younger, healthier patients.
This under-representation in clinical trials has also led to uncertainties about the safety of standard chemotherapy regimens in older patients, they said, who often have other health conditions to manage, alongside cancer.
In a secondary analysis, researchers led by by Mostafa Mohamed from the University of Rochester, New York, evaluated the association between primary treatment modifications to standard-of-care chemotherapy regimens and treatment tolerability.
The trial included 609 patients aged ≥ 70-years-old, who had advanced cancer alongside at least one age-related condition, such as impaired cognition, and who planned to start a new palliative chemotherapy regimen in the community oncology setting.
The most common cancer types were gastrointestinal cancer (37.4%) and lung cancer (28.6%).
The primary outcome was grade 3-5 adverse events within three months of chemotherapy initiation.
Secondary outcomes included patient-reported functional decline and combined adverse outcomes, which incorporated clinician-rated toxic effects, patient-reported functional decline, and six-month overall survival.
Overall, 281 patients (46.1%) received a primary treatment modification, most often a dose reduction (71.9%) or a scheduling change (11.7%).
Those who received primary treatment modifications had a 15% lower risk for grades 3-5 adverse effects (relative risk [RR], 0.85) and a 20% lower risk for patient-reported functional decline (RR, 0.80) than those who received standard treatment.
Patients receiving treatment modifications had 32% lower risk for a worse combined adverse outcome (odds ratio, 0.68).
Cancer type may matter as well. When looking at outcomes by cancer type, patients with gastrointestinal cancers who received a primary treatment modification had a lower risk for toxic effects (RR, 0.82), whereas patients with lung cancer did not (RR, 1.03; 95% CI, 0.88-1.20).
The researchers said their findings “can help oncologists to choose the optimal drug regimen, select a safe and effective initial dose, and undertake appropriate monitoring strategies to manage the clinical care of older people with advanced cancer”.
Their findings were published in JAMA Network Open.
Limitations
The authors said residual confounding may be present. Extremely healthy older patients may have been excluded due to study criteria, limiting generalisability. Also, there may be variation in toxicities due to inclusion of patients with multiple heterogeneous cancer.
Study details
Primary treatment modification and treatment tolerability among older chemotherapy recipients with advanced cancer
Mostafa Mohamed, David Rich, Supriya Mohile et al.
Published in JAMA Network Open on 15 February 2024
Abstract
Importance
Older adults with advanced cancer are less likely to tolerate treatment with cytotoxic chemotherapy compared with younger patients due to their ageing-related conditions. Hence, oncologists sometimes opt to employ primary treatment modifications (deviation from standard of care) during the first cycle of chemotherapy.
Objective
To examine the association between primary treatment modification and treatment tolerability in older adults with advanced cancer who were starting new palliative chemotherapy regimens.
Design, Setting, and Participants
This cohort study was a secondary analysis of the GAP70+ (Geriatric Assessment Intervention for Reducing Toxicity in Older Patients with Advanced Cancer) trial, which was conducted between July 2014 and March 2019. The GAP70+ trial included patients aged 70 or older who had advanced (ie incurable) cancer, had one or more geriatric assessment domain impairments, and planned to start a new palliative chemotherapy regimen. Data analysis was conducted in November 2022.
Exposures
Receipt of standard-of-care chemotherapy regimens vs primary treatment modification defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials (eg, primary dose reduction, schedule change).
Main Outcomes and Measures
Tolerability outcomes were assessed within three months of treatment. These outcomes included the following: (1) any grade 3 to 5 toxic effect, according to the National Cancer Institute Common Terminology Criteria for Adverse Events; (2) patient-reported functional decline, defined as the development of worse dependency in activities of daily living using scale scores; and (3) a composite adverse outcome (an end point that combined toxic effects, functional decline, and six-month overall survival). Multivariable cluster-weighted generalised estimating equation models examined the association between primary treatment modification and outcomes adjusting for covariates.
Results
This study included 609 patients with a mean (SD) age of 77.2 (5.2) years; more than half (333 [54.7%]) were men. Race and ethnicity was available for 607 patients: 39 (6.4%) were black, 539 (88.5%) were non-Hispanic white, and 29 (4.8%) were of other race or ethnicity. Nearly half (281 [46.1%]) received a primary modified treatment regimen. The most common cancer types were gastrointestinal cancer (228 [37.4%]) and lung cancer (174 [28.6%]). In multivariable analysis, primary treatment modification was associated with a reduced risk of grade 3 to 5 toxic effects (relative risk [RR], 0.85 [95% CI, 0.77-0.94]) and functional decline (RR, 0.80 [95% CI, 0.67-0.95]). Patients who received primary treatment modification had 32.0% lower odds of having a worse composite adverse outcome (odds ratio, 0.68 [95% CI, 0.48-0.97]).
Conclusions and Relevance
In this cohort study, primary treatment modification was associated with improved tolerability of chemotherapeutic regimens among older adults with advanced cancer and aging-related conditions. These findings may help optimise cancer treatment dosing in older adults with advanced cancer and ageing-related conditions.
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