medwireNews: Early results from the BEGONIA trial point to the potential of first-line treatment with datopotamab deruxtecan (Dato-DXd) plus durvalumab in people with advanced triple-negative breast cancer (TNBC).
The combination of the TROP2-directed antibody–drug conjugate and the PD-L1 inhibitor elicited “a robust response rate” and demonstrated “a manageable safety profile,” said presenter Peter Schmid (Barts Cancer Institute, London, UK) at the ESMO Breast Cancer Congress 2022 in Berlin, Germany.
Schmid explained that the phase 1b/2 platform study is investigating durvalumab in combination with other agents as first-line therapy for locally advanced or metastatic TNBC in a biomarker-unselected population.
The current presentation focused on the 29 patients aged a median of 51 years who received intravenous Dato-DXd at a dose of 6 mg/kg alongside durvalumab 1120 mg every 3 weeks until disease progression or intolerable toxicity. The majority (72.4%) had low levels of PD-L1 expression (<5%), 17.2% had high levels (≥5%), and the PD-L1 status was unknown for the remaining 10.3%.
Participants were followed up for a median of 3.9 months, during which time the combination achieved a confirmed objective response rate of 74% among the 27 evaluable patients. The responses were complete in 7% and partial in 67%.
All responses were ongoing at data cutoff, with the median duration unreached, highlighted the presenter. He added that “responses were observed regardless of PD-L1 expression,” which he believes “is an important finding of this trial.”
The safety profile of the combination was “consistent with the known profile of the individual agents and no new safety signals emerged during this trial,” said Schmid.
All patients experienced at least one adverse event (AE) of any grade, with the most common being stomatitis, in 69%, followed by alopecia and nausea, each in 66%. The incidence of AEs of grade 3 or 4 was 28%, with stomatitis once again being the most frequent (grade 3 in 14%, no grade 4 cases).
A total of 14% of participants required a dose reduction of Dato-DXd, all due to stomatitis, while 3% and 14% had to delay doses of Dato-DXd and durvalumab, respectively. Seven percent discontinued all study treatments due to AEs.
Schmid noted that trial management guidelines have been updated and prophylactic measures introduced “to reduce the incidence and severity of stomatitis.”
And he concluded that enrollment to the expansion phase of the Dato-DXd plus durvalumab arm of the trial is ongoing, and “follow-up continues in order to determine duration of response” as well as progression-free and overall survival.
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