Most breast cancer RT appears safe with ADCs, but T-DM1 raises concern after brain SRS

KEY POINTS

• This systematic review and meta-analysis included 29 studies and 3,817 patients receiving at least one RT course during or close to antibody-drug conjugate therapy. The agents represented were T-DM1, T-DXd and sacituzumab govitecan across adjuvant, intracranial and extracranial metastatic settings.
• Across all settings, the pooled rate of grade ≥3 treatment-related adverse events was 4%. Drug-specific estimates were similarly low at 4% with T-DM1, 3% with T-DXd and 4% with sacituzumab govitecan, although between-study heterogeneity was substantial.
• Postoperative breast RT had a particularly reassuring profile. Across nine studies, pooled grade ≥3 toxicity was 1%, with estimates of 1% for T-DM1 and 3% for T-DXd. Grade ≥3 pneumonitis was not observed in the four adjuvant studies reporting this endpoint.
• The main safety signal emerged with intracranial stereotactic RT. Across 13 studies, grade ≥3 complications occurred in 8%, while pooled severe radiation necrosis was approximately 9%.
• T-DM1 carried the clearest intracranial signal, with a pooled grade ≥3 toxicity estimate of 13%, compared with 6% for T-DXd and 1% for sacituzumab govitecan. Several T-DM1 series reported markedly higher radiation-necrosis rates, although confidence intervals were wide.
• Severe extracranial toxicity remained uncommon. Across all settings, pooled grade ≥3 pneumonitis and hematologic toxicity were both approximately 0%, and permanent ADC discontinuation specifically because of RT-related complications was uncommon.
• Interpretation is limited by inconsistent definitions of “concurrent” therapy and predominantly retrospective evidence. Most non-randomized studies had serious risk of bias, follow-up was often short for detecting radiation necrosis, and RT dose-volume details were inconsistently reported.

CLINICAL TAKEAWAY

SOURCE

Radiotherapy and Oncology