Quality of Life of Patients on Adjuvant Treatment for HER2-Positive Breast Cancer

Trastuzumab Emtansine in the Treatment of Residual Invasive Disease

Patients with HER2-positive breast tumors who still have residual invasive disease after neoadjuvant therapy have a higher likelihood of disease recurrence or death compared to patients who achieve complete pathological response. The KATHERINE clinical trial assessed the efficacy of adjuvant treatment in patients who had residual invasive disease (in the breast or axillary lymph nodes) before tumor resection following neoadjuvant chemotherapy in combination with HER2-targeted therapy.

It was shown that therapy with trastuzumab emtansine (T-DM1), a conjugate of the HER2 inhibitor trastuzumab and the microtubule inhibitor emtansine, significantly reduced the risk of invasive disease recurrence compared to trastuzumab therapy (hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.39–0.64; p < 0.001). Patients were randomized to 14 cycles of T-DM1 treatment (n = 743) at a dose of 3.6 mg/kg or trastuzumab (n = 743) at a dose of 6 mg/kg, with medication administered intravenously every 3 weeks.

Observed Safety Profile

Adverse events that occurred significantly more frequently in the T-DM1 arm included fatigue, nausea, decreased platelet count, elevated liver enzymes, headache, epistaxis, peripheral sensory neuropathy, and dry mouth. Most of these events were grade 1 or 2, but in the T-DM1 group, there were more grade ≥ 3 adverse events (26% vs. 15% in the trastuzumab arm) and adverse events leading to therapy discontinuation (18% vs. 2%).

An important factor in evaluating treatment is how it is perceived by the patients themselves. The KATHERINE study aimed to assess the clinical impact of T-DM1 treatment-related adverse effects compared to trastuzumab using patient-reported outcomes (PROs).

Quality of Life Questionnaires

The PROs were assessed using the quality of life questionnaire QLQ-C30 developed by the European Organisation for Research and Treatment of Cancer (EORTC) and its specific module for breast cancer (QLQ-BR23). These questionnaires evaluated overall well-being, physical, emotional, social, and cognitive functions, levels of pain and fatigue, sexual function, and body image satisfaction. Patients filled out the questionnaires at study entry and on day 1 of treatment cycles 5 and 11, within 30 days after treatment completion, and during follow-up visits at 6 and 12 months post-therapy.

Results

Questionnaires from the study entry and at least one subsequent follow-up were assessable for 82% of patients in the T-DM1 group and 86% of patients in the trastuzumab arm. No clinically significant changes in mean QLQ-C30 or QLQ-BR23 scores were observed in either group.

Clinically significant declines in some of the assessed points were more frequent in the T-DM1 group: role functioning (49% vs. 41%), loss of appetite (38% vs. 28%), constipation (47% vs. 38%), fatigue (66% vs. 60%), nausea/vomiting (39% vs. 30%), and systemic therapy side effects (49% vs. 36%). However, these differences were not observed 6 months after treatment completion, except for role functioning (23% vs. 16%).

Conclusion

It appears that the adverse events associated with adjuvant T-DM1 treatment had only a minimal impact on patients' quality of life. The average changes in scores from baseline were comparable between both study arms and did not reach the threshold of clinical significance. Although more patients in the T-DM1 group reported clinically significant worsening of some assessed parameters or symptoms during the study, this balance equalized within 6 months post-treatment.

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Source: Conte P., Schneeweiss A., Loibl S. et al. Patient-reported outcomes from KATHERINE: a phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer. Cancer 2020 Apr 14, doi: 10.1002/cncr.32873 [Epub ahead of print].