What are the recommended prophylactic measures for managing or mitigating diarrhea when pertuzumab is combined with trastuzumab deruxtecan, given toxicity risk with each individually?

My understanding is that prophylactic anti-diarrheals were not required in the trial but left to institutional discretion. While the rate of diarrhea in DB-09 was 56%, most of these were Grade 1-2 (only 7% were Grade 3 or higher). As such, I am not starting antidiarrheals prophylactically, but I do ...

Given the overlapping gastrointestinal toxicity profiles of pertuzumab and trastuzumab deruxtecan, I take a proactive approach to diarrhea management. I counsel patients upfront that diarrhea is common and emphasize early intervention rather than waiting for symptoms to worsen. I routinely encourage...

Pertuzumab-associated diarrhea is driven by EGFR/HER3 heterodimerization blockade, causing excess chloride secretion in the gut, with an incidence of 28–72% across studies and highest rates during the first cycle, decreasing thereafter (Swain et al., PMID 28057664). T-DXd-associated diarrhea (~12–30...