Enhertu Maintains QOL, Slows Pain in HR+/HER2 Metastatic Breast Cancer

Enhertu (T-DXd; fam-trastuzumab deruxtecan-nxki) reduced deterioration in physical and role functioning (ability to perform tasks) and pain compared with treatment of physician’s choice (TPC) in patients with hormone receptor (HR)-positive, HER2-low or -ultralow metastatic (spreading) breast cancer, according to quality-of-life (QOL) data presented at the 2024 ESMO Congress.

The data, which were presented about the randomized phase 3 DESTINY-Breast06 trial, evaluated patients with HR-positive, HER2-low and patients with HR-positive, HER2-ultralow disease. Patients were randomly assigned on a 1:1 basis to receive 5.4 milligrams/kilograms T-DXd every three weeks or TPC chemotherapy including capecitabine, nab-paclitaxel, or paclitaxel. The patient-reported responses were assessed for both the intent-to-treat population (ITT; 436 patients for Enhertu and 430 patients for TPC) and the HER2-low group (359 patients and 354 patients, respectively).

The median duration of treatment was 11 months with Enhertu versus 5.6 months with TPC chemotherapy. The European Organisation for Research and Treatment of Cancer QLQ-C30 oncology-specific questionnaire (general oncology-specific questionnaire that measures the quality of life of cancer patients) and the QLQ-BR45 breast cancer­-specific questionnaire (breast cancer-specific questionnaire that assesses the quality of life of patients) were assessed at baseline, every three weeks until the end of treatment, and then every three weeks until second progression or death.

Patient-reported responses (PROs) from the DESTINY-Breast06 trial showed a similar median time to deterioration (TTD; time it takes for a condition to worsen) overall between the two groups in the ITT population and the HER2-low subgroup, but differences in some symptoms. The median time to pain deterioration (time it takes for pain to worsen) showed the most significant improvement for Enhertu at 22 months versus 6.3 months for TPC.

“The global health/QOL was observed over 31 weeks for both groups. The QOL scores did not change from the baseline to a clinically significant degree,” Dr. Xichun Hu, of the department of medical oncology in Fudan University Shanghai Cancer Center and professor in the department of oncology at Shanghai Medical College at Fudan University in Shanghai, China, said in his presentation. “Time to deterioration in QOL was similar with the two treatment groups. [Enhertu] reduced the risk of clinically meaningful deterioration in pain by 49%.”

The prior lines of therapy received by patients in this study included at least two lines of endocrine therapy with or without targeted therapy for metastatic breast cancer or those who had disease progression within six months of starting first-line (first treatment) endocrine therapy and CDK4/6 inhibitor therapy for metastatic breast cancer or recurrence within 24 months after starting chemotherapy with endocrine therapy.

In the primary analysis of the trial, investigators reported that it met its primary goal of progression-free survival (PFS; how long a person lives without their disease worsening) with Enhertu showing 13.2 months compared with 8.1 months for TPC.

The QLQ-C30 evaluated Global Health Status (GHS)/QOL, physical, emotional, role, social and cognitive functional scales and symptom scales. Hu reported that overall GHS/QOL were maintained over 31 weeks with Enhertu and TPC in the ITT population, with a mean baseline GHS score of 69.51 and 65.88, respectively. With a mean change of 10 points from baseline being considered meaningful, neither group showed any significant shifts over time with 65.8% compliance in the Enhertu group and 69.8% in the TPC group. The median time to deterioration in GHS/QOL was 11.3 months for Enhertu and 10.5 months for TPC.

In terms of pain, Enhertu significantly reduced the risk of deterioration per QLQ-C30. It also reduced the risk of deterioration in several other outcomes including physical functioning, role functioning, emotional functioning and fatigue. Enhertu was worse than TPC in nausea/vomiting, appetite loss and constipation.

The QLQ-BR45 evaluated multi-item scores including skin mycosis symptoms, body image, sexual functioning, group symptoms and breast symptoms. The TPC group showed a clinically meaningful deterioration based on this measure, reaching a 10-point adjusted mean change from baseline at approximately seven weeks and continuing to show 10 or more points difference through 31 weeks. However, the Enhertu group did not differ significantly from baseline. “Among the components in the BR45 questionnaire, clinically meaningful deterioration of skin and mucosal system was observed with TPC, but not with [Enhertu],” said Hu.

He emphasized that with a duration of treatment approximately double that of TPC, Enhertu maintained QOL as well as delaying time to deterioration in some areas. “Gastrointestinal [GI] symptoms reported by patients who received T-DXd highlight the importance of implementing antiemetic prophylaxis in the clinic. Further investigation of the effect of antiemetic prophylaxis on GI symptoms and associated QOL in patients receiving T-DXd is warranted,” said Hu.

He added that the GI side effects reported in the QOL data “did not appear to be detrimental to overall preservation of QOL and were consistent with the safety profile reported by study investigators.”

“PRO results describing patients’ perspective further support [Enhertu] as a new therapeutic option following one or more endocrine-based therapies for patients with HER2-low and HER2-ultralow, HR-positive metastatic breast cancer,” he concluded.

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