Treatment Modifications Improve Tolerability Without Compromising Efficacy in Older Adults With Advanced Cancer

Primary treatment modifications during the first cycle of chemotherapy can improve tolerability without compromising efficacy in older patients with advanced cancer and aging-related conditions, according to research published in JAMA Network Open.

Researchers found that patients with primary treatment modifications were less likely than those who received standard treatment to experience grade 3-5 adverse events (AEs), report functional decline, or die within 6 months of starting treatment.

The researchers compared standard chemotherapy to primary treatment modification in patients from the GAP70+ trial. The trial enrolled patients who were 70 years of age or older, had advanced cancer, and had at least 1 geriatric assessment domain impairment.

The cohort included 609 patients with a mean age of 77.2 years. More than half of patients were men (54.7%), most were White (88.5%), and most had stage IV cancer (86.4%). The most common cancer types were gastrointestinal (37.4%) and lung (28.6%) cancer.

A total of 281 patients (46.1%) received a primary treatment modification, typically a dose reduction (71.9%) or schedule change (11.7%).

Results

In the overall cohort, 66.5% of patients had a grade 3 or higher AE within 3 months of starting treatment. Primary treatment modification was associated 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 dividing patients by cancer type, primary treatment modification was associated with a lower 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) except lung cancer (RR, 1.03; 95% CI, 0.88-1.20).

A total of 153 patients (28.0%) reported experiencing functional decline, defined as “the development of worse dependency in activities of daily living.” Primary treatment modification was associated with a lower risk of functional decline in an adjusted analysis (RR, 0.80; 95% CI, 0.67-0.95).

However, when the researchers divided patients by cancer type, there were no significant differences in functional decline between patients who received primary treatment modifications and those who received standard care.

The researchers also assessed a composite adverse outcome, which incorporated clinician-rated 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 dying 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 dying within 6 months.

Patients who received primary treatment modifications were less likely than those who received standard care to have a worse composite outcome (odds ratio, 0.68; 95% CI, 0.48-0.97).

“[O]ur findings illustrate that primary treatment modification improved patient tolerability without compromising treatment efficacy,” the researchers wrote. “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 researchers noted, however, that additional research is needed to confirm these findings and provide insights regarding different cancers, treatment regimens, and specific treatment modifications.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor