Age, Comorbidities Increase Chance of Trastuzumab Discontinuation

Older age and comorbidities were associated with a higher risk of failing to complete trastuzumab therapy in a new study of older women with early-stage breast cancer, where nearly 20% failed to complete the treatment.

In a new study, though most older women with early-stage breast cancer completed trastuzumab therapy, almost 20% failed to complete the treatment. Older age and more comorbidities were associated with a higher risk of failing to complete the course of therapy.

“A significant proportion of women do not complete one year of therapy with trastuzumab, and more work is needed to understand toxicity and efficacy in this population,” said senior study author Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute in Boston, in an e-mail. She and her colleagues used Surveillance, Epidemiology, and End Results (SEER) data to identify 2,028 women aged at least 66 years diagnosed with stage I to III breast cancer who received trastuzumab between 2005 and 2009. Most patients (85.2%) received the drug along with chemotherapy.

Among the total cohort, 1,656 women (81.7%) completed the trastuzumab course, which was defined as at least 270 days of therapy. Most of the cohort (71.2%) were under 76 years of age, and 66.8% had a Charlson comorbidity score of 0; 11.1% had a comorbidity score of 2 or greater. The median duration of trastuzumab treatment was 357 days.

Older age was associated with a lower chance of completing trastuzumab therapy. Those between 66 and 70 years had a 86.1% rate, compared with 69.1% for those older than 80 years (P < .001). A comorbidity score of 2 or higher yielded a completion rate of 76%, significantly less than the 83% for those with a score of 0 (P = .03). When further stratified, these factors’ importance became more clear: a group of 582 women aged 66 to 70 years with no comorbidities had a completion rate of 85.9%, compared with a group of 69 women over 80 years of age with any comorbidities that had a 62.3% completion rate (P < .001).

Women of Hispanic/other/unknown origin also were less likely to complete the therapy, with an odds ratio for completion of 0.56 vs non-Hispanic white patients (P = .002). Tumor size, tumor grade, and number of positive nodes were not significantly correlated with trastuzumab treatment completion. Women who received a taxane-based chemotherapy regimen along with trastuzumab were most likely to complete the therapy, compared with other chemotherapy options.

“We observed a number of women who experienced severe cardiac toxicity with treatment, which may explain some of the premature treatment discontinuation,” Freedman said. There were 73 patients who were admitted to a hospital for cardiac events during the treatment period, including 2.6% of patients who completed trastuzumab and 8.1% of those who did not (P < .001). The authors concluded that incorporating older patients into clinical trials will allow for a better understanding of the treatment options and their effects, and that tailoring the treatment based on this information should yield improvements in disease recurrence and survival.