Cognition Worse With Combo Therapy Than With Endo Alone in Patients With Breast Cancer

Source: Irene M. Kang, MD, of City of Hope Comprehensive Cancer Center in Irvine, California,

From: medscape.com

TOPLINE:

In a prespecified secondary analysis of the RxPONDER trial, chemoendocrine therapy was associated with larger and more sustained declines in patient-reported cognitive function than endocrine therapy alone in both pre- and postmenopausal patients with hormone receptor-positive ERBB2-negative breast cancer over a period of 36 months. While cognitive function recovered to baseline with endocrine therapy alone, a persistent cognitive decline was observed in patients receiving combined therapy.

METHODOLOGY:

• Adjuvant endocrine therapy and chemotherapy reduce the risk for recurrence and improve survival in hormone receptor-positive ERBB2-negative breast cancer, but both therapies are associated with cancer-related cognitive impairment that can adversely affect quality of life. The RxPONDER trial found that postmenopausal women could omit chemotherapy, whereas premenopausal women benefited from it. However, the comparative effects of endocrine therapy alone vs chemoendocrine therapy on cancer-related cognitive function and the role of menopausal status remain unclear.
• Researchers conducted a prespecified secondary analysis of the multinational phase 3 RxPONDER trial, involving 568 women with hormone receptor-positive ERBB2-negative breast cancer, one to three involved lymph nodes, and Oncotype DX (21-gene recurrence score) ≤ 25. A total of 139 premenopausal (median age, 47.8 years) and 429 postmenopausal (median age, 62.3 years) women completed baseline patient-reported outcome questionnaires and were randomly assigned to receive either chemoendocrine therapy (n = 274) or endocrine therapy alone (n = 294).
• The primary outcome of this secondary analysis was change in cognitive function scores over time by treatment group and menopausal status. Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System Perceived Cognitive Function Concerns questionnaire, and scores were compared between treatment groups at baseline and at 6, 12, and 36 months.
• Proportions of participants with clinically meaningful change from baseline were calculated at each follow-up; a mean change of 3 or more T score points was defined as clinically meaningful, and participants were classified as having worse (decline of 3 or more points), better (increase of 3 or more points), or the same (within 3 points) cognitive function.
• During follow-up, 441 (78%), 431 (76%), and 334 (59%) patients completed cognitive questionnaires at 6, 12, and 36 months, respectively.

TAKEAWAY:

• Overall, chemoendocrine therapy showed a greater negative association with patient-reported cognitive impairment in both pre- and postmenopausal participants. In the endocrine therapy group, mean cognitive T scores decreased from baseline to 6 and 12 months but recovered at 36 months among premenopausal patients, whereas scores remained stable among postmenopausal patients.
• In the chemoendocrine therapy group, mean T scores decreased from baseline to 6 and 12 months and remained lower than baseline at 36 months among both pre- and postmenopausal women. The mean difference in cognitive function T scores between groups was -3.02 (P = .01) for premenopausal participants and -2.37 (P = .003) for postmenopausal participants.
• Regarding clinically meaningful change in cognitive function, 43% of premenopausal participants in both groups reported worse cognitive function at 12 months vs baseline; at 36 months, 42% vs 28% of patients in the chemoendocrine vs endocrine therapy group reported worse cognition. Among postmenopausal participants, 46% vs 30% of patients on chemoendocrine vs endocrine therapy reported worse cognition at 12 months; the proportion was 41% vs 36% at 36 months.
• Odds ratios for worse cognition comparing chemoendocrine with endocrine therapy were not statistically significant for premenopausal women at 6, 12, or 36 months; the odds were higher among postmenopausal women with chemoendocrine therapy at 6 and 12 months but were attenuated by 36 months. Looking at baseline symptom correlations, higher baseline anxiety correlated with lower baseline cognitive function (coefficients of correlation [r] for premenopausal and postmenopausal women, -0.52 and -0.45, respectively). Higher baseline fatigue correlated with lower baseline cognitive function (r, -0.48 and -0.59, respectively).
• In adjusted Cox regression analyses, neither baseline patient-reported cognitive function nor a decline at 12 months was associated with invasive disease-free survival or overall survival, with hazard ratios equal to 1.00 and not statistically significant. Exploratory analyses suggested lower mean cognitive function scores at 6 months after receiving anthracycline-containing regimens vs other regimens, but these comparisons were limited by small sample sizes.

IN PRACTICE:

“In this secondary analysis of the RxPONDER randomized clinical trial, [chemoendocrine therapy] therapy had a greater negative association with patient-reported [cancer-related cognitive impairment] compared to [endocrine therapy] alone among both pre and postmenopausal patients, a finding that was sustained over 36 months,” the authors wrote.

“While these data are unlikely to strongly sway chemotherapy recommendations when it is medically indicated, they can inform conversations about cognitive adverse effects over time for women with breast cancer, particularly in the setting of [chemoendocrine therapy],” and “this information also allows clinicians to more fully discuss the potential adverse effects of therapies with patients during shared decision-making about treatment options,” said Michelle C. Janelsins, PhD, MPH, and Allison Magnuson, DO, MS, both of the University of Rochester in Rochester, New York, in an accompanying editorial.