TROPION-Breast01 and DESTINY-Breast04: Antibody-Drug Conjugates of Benefit in Patients With Metastatic Breast Cancer

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The TROP-2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) significantly improved progression-free survival over standard chemotherapy in the TROPION-Breast01 trial involving patients with previously treated, hormone receptor–positive, HER2-negative, unresectable and/or metastatic breast cancer, thus meeting the study’s primary endpoint. Aditya Bardia, MD, MPH, FASCO, Director of Breast Cancer Research at Massachusetts General Hospital and Associate Professor at Harvard Medical School, Boston, presented the primary analysis of TROPION-Breast01 at a Presidential Session during the European Society for Medical Oncology (ESMO) Congress 2023.1

“The results overall support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive, HER2-negative breast cancer.”
— Aditya Bardia, MD, MPH, FASCO

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“After a small initial drop [in the Kaplan-Meier curve] in both arms, there’s a separation of the curves in favor of Dato-DXd that is maintained and, if anything, increases over time, with an overall hazard ratio of 0.63. All subgroups derived benefit,” Dr. Bardia reported. “The results overall support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive, HER2-negative breast cancer.”

Also presented at the ESMO Congress 2023 were updated results of DESTINY-Breast04. Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, reported a clinical benefit with the similar antibody-drug conjugate trastuzumab deruxtecan (T-DXd) that was consistent with the primary analysis.2

About TROPION-Breast01

TROPION-Breast01 enrolled 732 patients with inoperable or metastatic hormone receptor–positive, HER2-negative breast cancer who experienced disease progression on or were unsuitable for endocrine therapy and had previously received one or two lines of chemotherapy. Patients were randomly assigned to receive Dato-DXd at 6 mg/kg every 3 weeks or investigator’s choice of chemotherapy (eribulin, vinorelbine, gemcitabine, capecitabine). Dual primary endpoints were progression-free survival by blinded independent central review and overall survival. Median follow-up was 10.8 months.

Shanu Modi, MD

Shanu Modi, MD

“At data cutoff, approximately three times the number of patients were still on Dato-DXd as compared with standard chemotherapy,” Dr. Bardia noted.

Median progression-free survival was 6.9 months with -Dato-DXd vs 4.9 months with chemotherapy (hazard ratio [HR] = 0.63; P < .0001), with a consistent benefit observed across all subsets. At 9 months, 37.5% of the Dato-DXd arm vs 18.7% of the control arm were progression-free, as were 25.5% and 14.6%, respectively, at 12 months. The response rate was 36.4% with Dato-DXd and 22.9% with chemotherapy. Overall survival is not mature, but a trend favoring Dato-DXd (HR = 0.84) was observed, he said.

“Dato-DXd demonstrated a favorable, manageable safety profile, with no new safety signals…. In general, we saw the rate of grade ≥ 3 adverse events was lower in the intervention arm—less than half—as compared with the control arm (21% vs 45%), which is different from most studies. Similarly, the rate of treatment interruption was lower with Dato-DXd (12% vs 25%),” Dr. Bardia said.

Most treatment-related adverse events were of low grade and reported to be manageable. Oral mucositis or stomatitis led to treatment discontinuation in one patient treated with Dato-DXd. Ocular events were mostly dry eye. Nine patients (3%) treated with Dato-DXd had adjusted drug-related interstitial lung disease, and one of two grade ≥ 3 cases were later attributed to disease progression. The one treatment-related death occurred in the chemotherapy arm secondary to febrile neutropenia.


Dr. Modi presented updated survival data from the DESTINY-Breast04 trial of T-DXd, showing a sustained benefit in a population of 557 patients with HER2-low advanced breast cancer.2 After a median follow-up of 32.0 months, median overall survival was 22.9 months with T-DXd and 16.8 months with treatment of physician’s choice (HR = 0.69); median progression-free survival (by investigator assessment) was 8.8 and 4.2 months, respectively (HR = 0.36). For the subset of patients with hormone receptor–positive tumors, the hazard ratios were 0.69 for death and 0.37 for disease progression or death. For the hormone receptor–negative subset, these hazard ratios were 0.58 and 0.29, respectively.


  • In TROPION-Breast01, treatment with the antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) reduced the risk of disease progression or death by 37% and doubled the proportion of patients remaining free of disease progression at 9 months.
  • Dato-DXd was reported to be well tolerated, with fewer grade ≥ 3 adverse events than were observed with standard chemotherapy in the control arm.
  • How Dato-DXd should be positioned in the treatment of metastatic hormone receptor–positive, HER2-negative breast cancer remains unclear.

“In the hormone receptor–positive cohort and all patients, median overall survival was consistent with results from the primary analysis, showing a 31% reduction in the risk of death for T-DXd compared with treatment of physician’s choice,” Dr. Modi said. “At the landmark 2-year timepoint, all on standard chemotherapy had discontinued study treatment, whereas 15% of patients on T-DXd remain without any evidence of disease progression.” 

DISCLOSURE: Dr. Bardia has served as a consultant or advisor to Daiichi/AstraZeneca, Eli Lilly, Foundation Medicine, Genentech/Roche, Immunomedics/Gilead Sciences, Merck, Novartis, Pfizer, Phillips, Radius Health/Menarini, Spectrum Pharma, Taiho Pharmaceutical, and Sanofi. Dr. Modi has received honoraria from Daiichi Sankyo/Astra Zeneca and Seattle Genetics; has served as a consultant or advisor to AstraZeneca, Daiichi Sankyo, Genentech, GlaxoSmithKline, Eli Lilly, MacroGenics, Puma Biotechnology, Seattle Genetics, and Zymeworks; and has received institutional research funding from AstraZeneca, Daiichi Sankyo, Roche/Genentech, and Seattle Genetics.


1. Bardia A, Jhaveri K, Im SA, et al: Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: Primary results from the randomised phase III TROPION-Breast01 trial. ESMO Congress 2023. Abstract LBA11. Presented October 23, 2023.

2. Modi S, Jacot W, Iwata H, et al: Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Updated survival results of the randomized, phase III DESTINY-Breast04 study. ESMO Congress 2023. Abstract 376O. Presented October 21, 2023.

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