Patients with metastatic HR-positive breast cancer benefit from datopotamab deruxtecan

medwireNews: Among pretreated patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, datopotamab deruxtecan (Dato-DXd) significantly prolongs progression-free survival (PFS) relative to chemotherapy, suggest phase 3 data. The TROP2-directed antibody–drug conjugate (ADC) also had “a favorable and manageable safety profile, with no new safety signals,” said presenting author Aditya Bardia (Harvard Medical School, Boston, Massachusetts, USA) at the ESMO Congress 2023 in Madrid, Spain. The TROPION-Breast01 trial findings “support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor-positive breast cancer,” he continued. Outlining the background to the study, Bardia explained that chemotherapy is “widely utilized” for managing endocrine-resistant metastatic breast cancer, “but is associated with low response rate, poor prognosis, and significant toxicity including myelosuppression and peripheral neuropathy.” He added that Dato-DXd has “previously demonstrated promising antitumor activity” in this patient population and is given in a “convenient” schedule. The study authors therefore recruited 732 individuals with HR-positive, HER2-negative disease who had received one to two lines of chemotherapy in the metastatic setting and had either progressed on or were intolerant to endocrine therapy. At a median follow-up of 10.8 months, the co-primary endpoint of PFS by independent assessment was a median of 6.9 months for the 365 participants who were randomly assigned to receive intravenous Dato-DXd 6 mg/day every 3 weeks. This was significantly longer than the median of 4.9 months among their 367 counterparts given investigator’s choice of single-agent eribulin, vinorelbine, gemcitabine, or capecitabine instead, and corresponded to a significant 37% reduction in the risk for progression or death with the ADC. The PFS rates at 6, 9, and 12 months in the Dato-DXd arm were 53.3%, 37.5%, and 25.5%, respectively, compared with corresponding rates of 38.5%, 18.7%, and 14.6% in the chemotherapy arm. Overall survival is the other primary endpoint of the trial, but the data were not mature at the time of analysis, noted the presenter. He highlighted, however, that a trend favoring Dato-DXd was observed, with a hazard ratio for death of 0.84, and “the study is continuing to the next planned analysis for overall survival.” Grade 3 or worse treatment-related adverse events (TRAEs) occurred in a small proportion of patients in the Dato-DXd group, with the rate less than half that in the chemotherapy group, at 21% versus 45%. Stomatitis was the most common TRAE of this severity in the former group, observed in 6%, neutropenia in the latter, in 31%. The rate of dose reductions and interruptions due to TRAEs was also lower with Dato-DXd than chemotherapy, at 21% versus 30% and 12% versus 25%, respectively. But the rate of TRAE-related discontinuations was identical, at 3%. There were no fatal TRAEs among Dato-DXd-treated patients and one among those given chemotherapy. Discussant Sarat Chandarlapaty – from Memorial Sloan Kettering Cancer Center in New York, USA – said that on the basis of these results, he would “rather prescribe” Dato-DXd than more chemotherapy after one to two prior lines of chemotherapy in unselected patients with HR-positive, HER2-negative metastatic breast cancer. “But it leaves several unanswered questions,” he added, such as would Dato-DXd be preferable versus the two currently approved ADCs, sacituzumab govitecan and trastuzumab deruxtecan, and can these drugs be used in sequence, given that they have the same topoisomerase targeting payload. “And finally, would I rather prescribe Dato-DXd or some small molecules that might work in this context, like inhibitors of the PI3K kinase pathway,” said Chandarlapaty. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group ESMO Congress 2023; Madrid, Spain: 20–24 October

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Patients with metastatic HR-positive breast cancer benefit from datopotamab deruxtecan

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Related topics

Keynote webinar | Spotlight on antibody–drug conjugates in cancer