Chemo-endocrine therapy worse for cognition than endocrine therapy alone

Chemo-endocrine therapy has a greater negative effect on cancer-related cognitive impairment compared with endocrine therapy alone in both pre- and postmenopausal women, results from the RxPONDER PRO substudy showed.

Breast cancer treatment is associated with cancer-related cognitive impairment. However, the effect of endocrine therapy versus chemotherapy followed by endocrine therapy (chemo-endocrine therapy) is not well understood, nor is the impact of menopausal status [1,2]. Therefore, the impact of breast cancer treatment on cognition was explored in the RxPONDER PRO substudy (NCT01272037).

In this substudy, the 8-item Patient-Reported Outcomes Measurement Information System (PROMIS) Perceived Cognitive Function Concerns (PCF) questionnaire was completed at baseline and after 6, 12, and 36 months after randomisation of 568 patients (274 treated with chemo-endocrine therapy, 294 treated with endocrine therapy alone; 139 premenopausal, 429 postmenopausal). The primary endpoint of the substudy was the mean cognitive function score by treatment arm and menopausal status. Dr Irene Kang (City of Hope Orange County, CA, United States) presented the results [3].

In premenopausal participants treated with endocrine therapy alone, mean cognitive function score temporarily decreased after randomisation and returned to baseline value by 36 months. In contrast, in premenopausal patients treated with chemo-endocrine therapy the score decreased after randomisation and did not return to baseline value. The difference in longitudinal mean score between treatment arms (-3.02) was both statistically significant and clinically meaningful.

In postmenopausal participants treated with endocrine therapy alone, mean cognitive function score stayed stable during follow-up while in postmenopausal participants treated with chemo-endocrine therapy the score decreased after randomisation and did not return to baseline value. The difference in longitudinal mean score between treatment arms (-2.36) was statistically significant but not clinically meaningful.

The change in cognitive function was however heterogeneous. In both treatment groups and in both pre- and postmenopausal participants, most did not show a clinically meaningful worsening of cognitive function score during follow-up. Their score kept stable or was (clinically meaningful) better during follow-up. The odds of having worse cognitive function was highest in postmenopausal participants treated with chemo-endocrine therapy at 12 months after randomisation (OR 2.24; 95% CI 1.40–3.59).

“Chemo-endocrine therapy has a greater negative effect on cancer-related cognitive impairment compared with endocrine therapy alone both in pre- and postmenopausal women,” concluded Dr Kang. “In addition, the effect of chemo-endocrine therapy seems to persist over time in a significant portion of patients.”

1. Ahles TA, et al. J Clin Oncol. 2012;30:3675–3686.
2. Whittaker A, et al. Sci Rep. 2022;12:2135.
3. Kang I, et al. Patient-reported cognitive impairment in women participating in the RxPONDERR trial (SWOG S1007) by menopausal status. Abstract GS1-04, SABCS 2022, 6–10 December, San Antonio, TX, USA.

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Posted on 1 February 202328 March 2024