Dr Dent on the Potential Role of Dato-DXd for Immunotherapy-Ineligible TNBC

“Some would argue that [all patients] likely benefit from this antibody-drug conjugate. Ninety-one of the patients [had a] PD-L1 [CPS below 10], and 9% [of patients had] a PD-L1 [CPS above 10]. It looks like both of those groups benefited.”

Rebecca Dent, MD, MSc, FRCP, deputy chief executive officer (clinical) and a senior consultant at the National Cancer Centre Singapore, discussed the clinical implications of the phase 3 TROPION-Breast02 trial (NCT05374512) evaluating datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) vs investigator’s choice of chemotherapy in the frontline setting in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who were ineligible for immunotherapy.

Dent suggested that the benefits of this TROP-2–directed antibody-drug conjugate likely extend to most patients with TNBC. She noted that TROPION-Breast02 comprehensively assessed the efficacy of Dato-DXd across patients with varying levels of PD-L1 expression. In the study, 91% of patients were classified as having PD-L1–low disease with a combined positive score (CPS) of less than 10, whereas 9% of patients had disease that was designated as PD-L1 high with a CPS of at least 10. Both subgroups derived therapeutic benefit from Dato-DXd.

Dent described the ongoing efforts to further augment the efficacy of Dato-DXd in patients with TNBC. Ongoing trials that are exploring the combination of Dato-DXd with immune checkpoint inhibition, she explained, and more robust data may result from these combination trials over time.

Dent also noted that given the known biological expression profile of TROP-2 in the oral mucosa and the epithelium of the cornea, certain local toxicities were expected, including mucositis, which was predominantly reported as grade 1 and 2. At data cutoff, 90% of mucositis cases had successfully resolved, and no patients were required to exit the study because of mucositis. However, Dent emphasized that mucositis prophylaxis is necessary.

Regarding ocular surface adverse effects, Dent detailed the management procedures used in the trial, including baseline eye examinations, which were subsequently followed every 3 treatment cycles. She reiterated the importance of prophylaxis, specifically the use of eye drops, and stated that dose reductions might provide further help in managing these toxicities, given the understanding that ocular toxicities are potentially linked to TROP-2 expression.

A reassuring element of the Dato-DXd safety profile, Dent noted, pertains to interstitial lung disease (ILD) and pneumonitis. She reported that the occurrence of ILD/pneumonitis was rare in both treatment arms examined.