In a recent publication in the Journal of the American Medical Association Network, researchers conducted a cohort study and sought to investigate the correlation between primary treatment modification and tolerability of treatment among older adults with advanced cancer who were initiating new palliative chemotherapy regimens.
The authors wrote, “We hypothesized that older adults with advanced cancer who had primary treatment modification would have a lower risk of poor tolerability compared with older adults with advanced cancer who received standard-of-care regimens.”
This cohort study was a secondary analysis of the completed nationwide, multicenter, cluster-randomized GAP70+ (Geriatric Assessment Intervention for Reducing Toxicity in Older Patients with Advanced Cancer) trial. The study was conducted between July 2014 and March 2019 and was comprised of patients aged 70 years or older who had advanced (i.e., incurable) cancer, had one or more geriatric assessment domain impairments, and planned to begin a new palliative chemotherapy regimen. The researchers conducted data analysis in November 2022.
The study cohort involved 609 patients with an average age of 77.2 years; 54.2% were males, 88.5% were white, 6.4% were black, and 4.8% were of another race or ethnicity. The majority of the study cohort reported that 86.4% had stage IV cancer. The most common type of cancer included gastrointestinal and lung cancer, reported at 37.4% and 28.6%, respectively.
Of the study cohort, 281 patients (46.1%) received a primary treatment modification, usually a dose decrease (71.9%) or schedule change (11.7%).
The results revealed that 66.5% of patients had a grade 3 or higher adverse event (AE) within 3 months of starting treatment, and primary treatment modification was linked with a lower risk of grade 3 or higher AEs in an unadjusted analysis (relative risk [RR], 0.86; 95% CI, 0.77-0.96) and an adjusted analysis (RR, 0.85; 95% CI, 0.77-0.94).
In an adjusted analysis grouping patients by cancer type, primary treatment modification was linked with a lesser risk of grade 3 or higher AEs in patients with gastrointestinal cancer (RR, 0.82; 95% CI, 0.70-0.96) and other cancers (RR, 0.82; 95% CI, 0.67-1.00), but not among patients with lung cancer (RR, 1.03; 95% CI, 0.88-1.20).
In the cohort, 153 patients (28.0%) reported experiencing functional decline, defined as “the development of worse dependency in activities of daily living.” In multivariable analysis, patients with primary treatment modification had a 20.0% lower risk of functional decline than patients who received standard-of-care treatment (RR,?0.80; 95% CI, 0.67-0.95).
When grouped by cancer type, primary treatment modification was linked with a diminished risk of functional decline for patients with lung cancer (RR,?0.80; 95% CI, 0.48-1.34) and other cancer types (RR,?0.60; 95% CI, 0.35-1.01), but these decreases were not statistically noteworthy.
The researchers also evaluated a composite adverse outcome, which integrated clinician-rated adverse events (AEs), patient-reported functional decline, and overall survival. There were 114 patients (20.8%) who had a favorable composite outcome, defined as no grade 3 or higher AEs, no functional decline, and no death within 6 months of enrollment. An additional 333 patients (61.0%) had an intermediate composite outcome, defined as having grade 3 or higher AEs, having functional decline, or mortality within 6 months, and the remaining 99 patients (18.1%) had an unfavorable composite outcome, defined as having grade 3 or higher AEs or functional decline and mortality within 6 months.
The results also revealed that patients who received primary treatment modifications were less likely than those who received standard care to have a worse composite outcome, 32% lower odds (odds ratio, 0.68; 95% CI, 0.48-0.97).
Based on their findings, the authors concluded that in this cohort study, among older adults with advanced cancer and aging-related conditions, modification of primary treatment was correlated with improved tolerability of chemotherapeutic regimens, and these findings may aid in optimizing the dosing of cancer treatment in older adults with advanced cancer and aging-related conditions.
Lastly, the authors wrote, “Our findings illustrate that primary treatment modification improved patient tolerability without compromising treatment efficacy, as assessed through a composite adverse outcome measure. This information 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.”
The authors also indicated that more studies are warranted to confirm their findings.
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