Editor’s Note: The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting was held in Chicago, USA, from May 31 to June 4. At this year’s ASCO conference, the TROPION-Breast01 study (Oral Abstract Session: Abstract No. 1006) once again attracted attention and discussion. Professor Sonia Pernas from the Institut Català d'Oncologia presented a special report on June 1 from 16:24 to 16:36 (Beijing time: June 2, 05:24 to 05:36, Hall B1 | Live Stream). "Oncology Frontier" invited Professor Peng Yuan from the Chinese Academy of Medical Sciences Cancer Hospital to interpret the findings.

Study Overview

Abstract No. (Presentation Type): 1006 (Oral Abstract Session)

English Title: Datopotamab Deruxtecan (Dato-DXd) vs Chemotherapy (CT) in Previously Treated Inoperable or Metastatic Hormone Receptor-Positive, HER2-Negative (HR+/HER2–) Breast Cancer (BC): Patient-Reported Outcomes (PROs) from the TROPION-Breast01 Study.

Background

In the preliminary analysis of the phase III TROPION-Breast01 study (NCT05104866), Dato-DXd showed a significant improvement in progression-free survival (PFS) compared to investigator’s choice chemotherapy (ICC) (HR 0.63 [95% CI 0.52-0.76]; P<0.0001). This study reports on the patient-reported outcomes (PROs) from TROPION-Breast01.

Methods

A total of 732 patients with inoperable or metastatic HR+/HER2- breast cancer (who had received 1-2 lines of chemotherapy, progressed on endocrine therapy, or were unsuitable for endocrine therapy) were randomized 1:1 to receive Dato-DXd (6 mg/kg Q3W, n=365) or ICC (eribulin, vinorelbine, capecitabine, or gemcitabine, n=367). PROs, as secondary endpoints, included time to deterioration (TTD) in disease-related quality of life (based on global health status [GHS]/QoL), time to physical functioning deterioration, and time to pain (based on EORTC QLQ-C30).

Results

PRO questionnaire compliance at baseline was 82.5% in both groups, remaining similar over time. The initial analysis showed that, compared to the ICC group, the median TTD for Dato-DXd was 3.4 months vs. 2.1 months (HR 0.85 [95% CI 0.68-1.06]), the time to physical functioning deterioration was 5.6 months vs. 3.5 months (HR 0.77 [95% CI 0.61-0.99]), and the time to pain was 3.5 months vs. 2.8 months (HR 0.85 [95% CI 0.68-1.07]). Confirmed TTD analysis (sensitivity analysis) showed that, compared to the ICC group, the median TTD for Dato-DXd was 9.0 months vs. 4.8 months (HR 0.76 [95% CI 0.58-0.98]), time to physical functioning deterioration was 12.5 months vs. 6.2 months (HR 0.77 [95% CI 0.59-1.01]), and time to pain was 9.0 months vs. 5.5 months (HR 0.72 [95% CI 0.55-0.94]). The table below shows the TTD for other selected functional and symptom scales from the EORTC. Patient-reported symptomatic adverse events (AEs) (measured by PRO-CTCAE and EORTC) generally aligned with clinician-reported safety data, and patient-reported treatment tolerability (measured by PGI-TT) was comparable between groups.

Conclusion

In the TROPION-Breast01 study, compared to the ICC group, the Dato-DXd group showed delayed TTD in GHS/QoL, physical functioning, pain, and most other symptom and function scales. PRO data complement the initial analysis demonstrating improved efficacy and manageable safety of Dato-DXd compared to ICC, supporting Dato-DXd as a potential, well-tolerated treatment option for this setting.

Expert Commentary

In HR+/HER2- advanced breast cancer, the preferred treatment remains endocrine therapy combined with CDK4/6 inhibitors, but there is no consensus on treatment options for patients who fail first-line therapy. These options include cross-line treatment with CDK4/6 inhibitors, other targeted therapies (PI3K inhibitors, PAM pathway inhibitors, HDAC inhibitors, etc.), chemotherapy, and ADC drugs. ADC drugs, with their unique targeted cytotoxicity, have garnered significant attention from experts and scholars. Promising candidates in this field include trastuzumab deruxtecan targeting HER2, sacituzumab govitecan targeting TROP-2, and Dato-DXd. The initial TROPION-Breast01 study demonstrated the efficacy (PFS) of Dato-DXd, and this further analysis reports on the secondary endpoint PROs, showing a quality of life advantage for Dato-DXd. These results further solidify Dato-DXd’s role as an effective treatment option for advanced HR+/HER2- breast cancer.