Is the toxicity of adjuvant aromatase inhibitor therapy underestimated? Complementary information from patient-reported outcomes (PROs)

Abstract

Adjuvant endocrine treatment-related adverse effects have a strong impact on patients' quality of life and thereby limit therapy's risk benefit ratio resulting in morbidity and treatment discontinuation. Still, many AI adverse effects remain untreated given that they are unrecognized by conservative methods (e.g., proxy ratings). The ability of complementary patient-reported outcomes (PROs) to provide a more comprehensive assessment of side-effects is to be explored. A cross-sectional study sample of 280 postmenopausal, early stage breast cancer patients was subjected to a comprehensive PRO assessment (FACT-B/+ES) at their after-care appointment. Prevalence and severity of patient-reported physical side-effects and psychosocial burden related to adjuvant AI therapy were compared with prevalences derived from pivotal phase IV trials (ATAC 2005, BIG1-98 2005). Across all symptom categories, highest prevalence rates were found for joint pain (59.6%), hot flushes (52%), lost interest in sexual intercourse (51.4%), and lack of energy (40.3%). Overall, PROs resulted in significantly higher prevalence rates as compared to physician ratings for all symptoms published in pivotal clinical trials except vaginal bleeding and nausea. The treatment duration exerted no significant impact on symptom frequency (P > 0.05). Established prevalence rates of endocrine treatment-related toxicity seem to be underestimated. The incorporation of PRO data should be mandatory or at least highly recommended in clinical treatment planning to arrive at a more accurate assessment of a patient's actual symptom burden enabling improved individualized management of side-effects and mediating the preservation of treatment adherence.

Risk factors for joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes

“…For Sestak et al's study [5], anastrozole-related joint symptoms (35.2 %) were collected in free-text format on the case report form but it is not certain whether all joint symptoms were covered. However, self-reported data showed that 47 % of subjects reported suffering joint pain and 44 % joint stiffness [4], while the percentage suffering joint pain was 59.6 % as recorded from PROs [8]. Values obtained from PROs thus tend to be higher than those obtained by physicians or from [5], but we collected data for both first appearance and worsening from baseline symptoms.…”

The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents

“…The available drugs letrozole, anastrozole, and exemestane are widely used and effective in the treatment of breast cancer, but their use is compromised by side effects that result in non-compliance and poor quality of life for breast cancer patients [10,[19][20][21]37]. Toxicities are one of the major reasons for discontinuation of AIs, with the most common adherencelimiting toxicity being the AI-associated musculoskeletal syndrome [10,20,37,38]. It follows that it is important to develop more tolerable and effective drugs as the next generation of AIs.…”

Weight gain during adjuvant endocrine treatment for early-stage breast cancer: What is the evidence?

“…In a third study (no information on how long the women were on an AI), 48.7 % reported weight gain-53 % of women whom had natural menopause compared to 43 % who had induced menopause [42]. In a fourth study of women on AI for an average of 27.8 months (range 0.5-101 months), 33 % reported weight gain [43].…”