Trastuzumab Deruxtecan Elicits Superior HRQOL in HER2+ Metastatic Breast Cancer

Patient-reported outcomes, including time to definitive deterioration of global health status and overall quality of life (QOL) with fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive metastatic breast cancer reflected the regimen’s favorable risk-benefit profile in the phase 3 DESTINY-Breast02 trial (NCT03523585), according to findings presented during the 2023 ESMO Breast Cancer Annual Congress.

Global health status and health-related QOL outcomes were collected using oncology-specific questionnaires from patients receiving either trastuzumab deruxtecan or vs treatment of physician’s choice (TPC) on the study. The mean global health score at baseline for trastuzumab deruxtecan and TPC were 64.6 (standard deviation [SD], 21.7) and 65 (SD, 22.8), respectively, and was maintained until cycles 39 and 21, respectively. At this point less than 10% of patients were reporting and results were deemed to be no longer information, according to investigators.

The analysis was conducted using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 questionnaire (EORTC QLQ-C30). The median time to definitive deterioration of global health status and overall QOL was 14.1 months (95% CI, 10.4-18.7) in the trastuzumab deruxtecan arm vs 5.9 months (95% CI, 4.3-7.9) in the TPC arm (HR, 0.5573; 95% CI, 0.4376-0.7099; P < .0001).1

The median time to deterioration of physical functioning using EORTC QLQ-C30 was 18.7 months (95% CI, 15.5-22.9) vs 6.8 months (95% CI, 5.7-8.8) in the trastuzumab deruxtecan and TPC arms, respectively (HR, 0.4637; 95% CI, 0.3575-0.6014; P < .0001). Regarding pain symptoms, the median time to deterioration was 18.7 months (95% CI, 14.1-23.8) vs 5.8 months (95% CI, 5.0-7.0), respectively (HR, 0.3779; 95% CI, 0.2941-0.4857; P < .0001).

“To assess QOL from a patient’s perspective, PROs were measured at prespecified time points—during chemotherapy, end of treatment, and during follow-up,” Tanja N. Fehm, MD, said in a presentation of the data. Fehm is a specialist in gynecologic oncology at the University Hospital Düsseldorf and director of the Clinic for Gynecology and Obstetrics with the DKG-certified Gynecological Cancer Center in Dusseldorf, Germany. “The main analysis included change from baseline and/or time to definitive deterioration. In general compliance for the health-related patient questionnaire was high, the completion rate was more than 92% at baseline and more than 80% at cycles 3 to 39, after which the number of patients was less than 10%.... Global health status and health-related QOL were the primary PRO variables of interest. A 10-point change was considered clinically meaningful.”

Other reported scales included emotional functioning and social functioning. The median time to deterioration of emotional functioning with trastuzumab deruxtecan was 21.4 months (95% CI, 16.9-not estimable [NE]) vs 10.7 months (95% CI, 6.9-15.4) with TPC (HR, 0.67; 95% CI, 0.51-0.88; P < .0001). The median time to delay in social functioning was 18.7 months (95% CI, 13.9-28.8) compared with 6.3 months (95% CI, 4.9-8.8) in the investigative and control arms, respectively (HR, 0.54; 95% CI, 0.42-0.70; P < .0001).1

Definitive deterioration was also evaluated using the EuroQol5-dimension, 5-level questionnaire (EQ-5D-5L) and results further highlighted the delay in deterioration and time to symptoms with trastuzumab deruxtecan. Specifically, the median time to definitive deterioration of EQ-5D-5L visual analogue scale was 16.6 months (95% CI, 13.6-20.2) in the investigative arm vs 7.3 months (95% CI, 5.8-10.6) in the control arm (HR, 0.5906; 95% CI, 0.4583-0.7610; P < .001).1

Secondary PRO variables of interest were assessed using the EORTC quality of life breast cancer questionnaire (QLQ-BR45). The median time to deterioration in arm symptoms was 18.3 months (95% CI, 13.9-21.2) with trastuzumab deruxtecan and 8.8 months (95% CI, 6.1-11.6) with TPC (HR, 0.57; 95% CI, 0.44-0.75; P < .0001). The median time to deterioration of breast symptoms was NE (95% CI, 30.3-NE) in the trastuzumab deruxtecan arm vs 18.1 months (95% CI, 12.5-NE) in the TPC arm (HR, 0.42; 95% CI, 0.29-0.59; P < .0001).1

The mean change from baseline in EORTC QLQ-C30 nausea and vomiting score was 8.3 (SD, 16.6) in the trastuzumab deruxtecan arm and 8.1 (SD, 17.1) in the TPC arm. “An increase in nausea/vomiting scores was seen [in the trastuzumab deruxtecan arm] but only clinically relevant in the early cycles after which scores decreased and remained stable over time. These data underline the importance of proper prophylaxis for nausea and vomiting when starting a treatment,” Fehm said.

In the trial, 608 patients with pathologically confirmed HER2-positive metastatic breast cancer who had previously received T-DM1 were randomly assigned to receive trastuzumab deruxtecan (n = 406) or TPC (n = 202), which could be capecitabine with either trastuzumab (Herceptin) or lapatinib (Tykerb).1,2

Baseline characteristics were well balanced between the arms with a median age of 54.2 years (range, 22.4-88.5) and 54.7 years (range, 24.7-86.5) in the trastuzumab deruxtecan and TPC arms, respectively. Most patients had a HER2 status of 3+ per immunohistochemistry—80.3% of patients in the trastuzumab deruxtecan arm vs 78.7% in the TPC arm. An ECOG performance status of 0, 1 or 2 was reported among 56.2%, 43.6%, and 0.2% of patients, respectively, in the trastuzumab deruxtecan arm and 59.9%, 40.1%, and 0% of patients, respectively, in the TPC arm.1,2

Most patients had hormone receptor–positive disease (58.6% and 58.4%, respectively), had visceral disease (77.8% and 79.2%), and did not have brain metastases at baseline (81.8% and 82.2%). The median number of prior lines of therapy in the metastatic setting in both arms was 2.1,2

As previously reported, the median progression-free survival (PFS) with trastuzumab deruxtecan was 17.8 months (95% CI, 14.3-20.8) vs 6.9 months (95% CI, 5.5-8.4) with TPC (HR, 0.3589; 95% CI, 0.2840-0.4535; P < .000001).1,2 The median follow-up was 21.5 months (range, 0.1-45.6) and 18.6 months (range, 0-45.7), respectively.

The 12-month PFS rates in the trastuzumab deruxtecan and TPC arms were 62.3% (95% CI, 57.0%-67.1%) vs 27.2% (95% CI, 20.1%-34.8%), respectively. The 24-month PFS rates were 42.2% (95% CI, 36.5%-47.8%) vs 13.9% (95% CI, 7.9%-21.6%), respectively.

In terms of safety outcomes from the DESTINY-Breast02 trial, the most common drug-related treatment-emergent adverse effects (TEAEs) associated with drug discontinuation were pneumonitis (6.2%) and interstitial lung disease (3.2%) in the trastuzumab deruxtecan arm (n = 404) and palmar-plantar erythrodysesthesia (1.5%) in the TPC arm (n = 195). Dose reductions were most commonly reported with nausea (5.4%) in the trastuzumab deruxtecan arm and palmar-plantar erythrodysesthesia (23.6%) in the TPC arm.

The median treatment duration was 11.3 months with trastuzumab deruxtecan. In the TPC arm, the median treatment duration was 4.4 months with trastuzumab, 4.6 months with capecitabine, and 4.5 months with lapatinib.1,2

Disclosures: Dr Fehm reports advisory board compensation from Daiichi Sankyo, Novartis, Roche, Pfizer, MSD, and Teva Pharmaceuticals.

References

1. Fehm T, Cottone F, Dunton K, et al. DESTINY-Breast02 Investigators. Patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients with HER2-positive metastatic breast cancer. Presented at: 2023 ESMO Breast Cancer Congress; May 11-13, 2023; Berlin, Germany.
2. André F, Park YH, Kim SB, et al. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023;S0140-6736(23)00725-0. doi:10.1016/S0140-6736(23)00725-0