Datopotamab Deruxtecan Delays Quality-of-Life Deterioration Compared With Chemotherapy in HR-Positive, HER2-Negative Breast Cancer
Clinical Summary:
- Design/Population: TROPION-Breast01 compared datopotamab deruxtecan with investigator’s choice of chemotherapy in patients with previously treated inoperable or metastatic HR-positive, HER2-negative breast cancer.
- Key Outcomes: Datopotamab deruxtecan was associated with fewer grade ≥3 treatment-related adverse events compared with chemotherapy. Time to deterioration in global health status/quality of life, pain, and physical functioning was longer with datopotamab deruxtecan.
- Clinical Relevance: The safety and patient-reported outcome findings strengthen the clinical profile of datopotamab deruxtecan by showing that its previously demonstrated progression-free survival benefit was accompanied by lower rates of severe treatment-related toxicity and longer preservation of quality of life and functioning compared with chemotherapy.
Final safety and patient-reported outcome data from the phase 3 TROPION-Breast01 trial showed that datopotamab deruxtecan was associated with fewer high-grade treatment-related adverse events and delayed deterioration in quality of life, pain, and physical functioning compared with investigator’s choice of chemotherapy in patients with previously treated inoperable or metastatic HR-positive, HER2-negative breast cancer.
“Datopotamab deruxtecan is a TROP2-directed antibody-drug conjugate approved for the treatment of patients with unresectable or metastatic [HR]-positive, [HER2]-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease,” stated Hope Rugo, MD, City of Hope Comprehensive Cancer Center, Durate, California, and coauthors. “Approval was based on data from the phase 3 TROPION-Breast01 study, which assessed [datopotamab deruxtecan] compared with investigator’s choice of chemotherapy.”
TROPION-Breast01 randomized 732 patients to receive either 6.6 mg/kg of datopotamab deruxtecan every 3 weeks (n = 365) or investigator’s choice chemotherapy including eribulin, capecitabine, vinorelbine, or gemcitabine (n = 367). The safety population included 360 patients who received datopotamab deruxtecan and 351 patients who received investigator’s choice chemotherapy.
At the final overall survival (OS) analysis, treatment-related adverse events occurred in 94.7% of patients receiving datopotamab deruxtecan and 86.3% of patients receiving chemotherapy. Grade ≥3 treatment-related adverse events were less than half as frequent with datopotamab deruxtecan (22.2% vs 45.6%). Treatment-related adverse events led to fewer dose interruptions with datopotamab deruxtecan than chemotherapy (15.8% vs 24.2%) and fewer dose reductions (24.2% vs 30.2%).
The most common treatment-related adverse events with datopotamab deruxtecan were nausea (51.9%), stomatitis (51.4%), and alopecia (36.4%). Grade ≥3 treatment-related adverse nausea and stomatitis were reported in 1.4% and 6.4% of patients, respectively. More than three-quarters of patients receiving datopotamab deruxtecan received prophylactic antiemetics.
Oral mucositis/stomatitis was the most common treatment-related adverse event of special interest with datopotamab deruxtecan, occurring in 57.2% of patients, including grade ≥3 events in 7.2% of patients. Most patients receiving datopotamab deruxtecan used prophylactic mouthwash, including 38.6% who received steroid mouthwash and 63.6% who received nonsteroid mouthwash.
Treatment-related ocular surface events occurred in 43.9% of patients receiving datopotamab deruxtecan but were predominantly low grade with grade ≥3 events in 1.9% of patients. Dry eye and keratitis were the most frequently reported ocular events. Artificial tears were used by 71.7% of patients in the datopotamab deruxtecan arm.
Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 3.9% of patients treated with datopotamab deruxtecan, including grade ≥3 events in 0.8% of patients. One death was reported. No adjudicated drug-related interstitial lung disease/pneumonitis occurred with chemotherapy.
The toxicity profile differed notably between treatments. Hematologic toxicity was more prominent with chemotherapy, including treatment-related neutropenia in 43.3% of patients compared with 11.7% receiving datopotamab deruxtecan. Grade ≥3 neutropenia occurred in 31.1% and 1.1%, respectively. Neuropathy and palmar-plantar erythrodysesthesia were also more frequent with chemotherapy.
Patient-reported outcomes further favored datopotamab deruxtecan. Time to both first and confirmed deterioration in global health status/quality of life, pain, and physical functioning was delayed compared with chemotherapy. Datopotamab deruxtecan also generally prolonged time to deterioration across other measures of symptoms and functioning, although nausea/vomiting, constipation, and breast symptoms did not favor the antibody-drug conjugate.
Patient-reported symptomatic adverse events were broadly consistent with clinician-reported safety findings. Patients receiving datopotamab deruxtecan reported less numbness or tingling, diarrhea, shortness of breath, and hand-foot syndrome, whereas mouth or throat sores, nausea, vomiting, constipation, hair loss, and dry eyes were reported less frequently with chemotherapy.
These findings complement the previously reported efficacy results from TROPION-Breast01, in which datopotamab deruxtecan significantly improved progression-free survival compared with chemotherapy (P < .0001). At the final analysis, however, no significant OS difference was observed.
“The totality of data from TROPION-Breast01 supports [datopotamab deruxtecan] as a treatment option,” concluded Dr Rugo et al.
Source:
Rugo HS, Jhaveri K, Pernas S, et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive HER2-negative breast cancer: Safety and patient-reported outcomes from the phase III TROPION-Breast01 study. ESMO Open. Published online: July 24, 2026. doi: 10.1016/j.esmoop.2026.108330
