Enhertu Maintains Quality of Life in Metastatic Breast Cancer Subgroup

Patients with HR-positive, HER2-low or -ultralow metastatic breast cancer (MBC) treated with Enhertu (trastuzumab deruxtecan) had a reduced deterioration in physical/role functioning and pain versus treatment of physician’s choice (TPC), according to quality-of-life (QOL) data presented at the 2024 ESMO Congress.

Patient-reported outcomes (PROs) from the DESTINY-Breast06 trial showed a similar median time to deterioration (TTD) overall between the two arms in the intent-to-treat (a group of patients originally assigned to a specific treatment in the trial regardless of whether they actually received it; ITT) population and the HER2-low subgroup; however, there were differences in some symptoms. The median time to pain deterioration 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 arms. 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 2 treatment arms. Enhertu reduced the risk of clinically meaningful deterioration in pain by 49%.”

The phase 3 DESTINY-Breast06 trial investigated the HR-positive, HER2-low population, as well as patients with HR-positive, HER2-ultralow disease. 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 MBC, those who had disease progression within six months of starting first-line endocrine therapy and CDK4/6 inhibitor therapy for MBC, or recurrence within 24 months after starting adjuvant endocrine therapy.

Patients were randomly assigned to receive Enhertu or TPC chemotherapy including capecitabine, nab-paclitaxel or paclitaxel.

In the primary analysis of the trial, investigators reported that it met its primary end point of progression-free survival (the time during and after treatment when a patient with cancer is alive without disease worsening) with Enhertu showing 13.2 months compared with 8.1 months for TPC.

The patient-reported outcomes were assessed for both the ITT population (436 patients for Enhertu and 430 patients for TPC) and the HER2-low group (359 patients treated with Enhertu and 354 treated with TPC). The median duration of treatment was 11 months with Enhertu versus 5.6 months with TPC chemotherapy. Several questionnaires assessing quality of life were completed by patients at baseline, every 3 weeks until the end of treatment, and then every 3 weeks until second progression or death.

Hu reported that overall Global Health Status/QOL were maintained over 31 weeks with Enhertu and TPC in the ITT population, with a mean baseline Global Health Status score of 69.51 and 65.88, respectively. With a mean change of 10 points from baseline being considered meaningful, neither arm showed any significant shifts over time with 65.8% compliance in the Enhertu arm and 69.8% in the TPC arm. Median time to deterioration in Global Health Status /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 another questionnaire used in this study. It also reduced 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.

Researchers used another questionnaire that assessed how patients reported regarding skin mycosis (fungal infections on the skin) symptoms, body image, sexual functioning, arm symptoms and breast symptoms. The TPC arm 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 point difference through 31 weeks. However, the Enhertu arm 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 [Enhertu] highlight the importance to implementing antiemetic prophylaxis in the clinic. Further investigation of the effect of antiemetic prophylaxis on GI symptoms and associated QOL in patients receiving [Enhertu] 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.”

“[Patient-reported outcome] 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 MBC,” he concluded.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.