Key Clinical Trials in the First-Line Treatment of HER2+ Metastatic Breast Cancer

The discussion turns to several ongoing clinical trials in the first-line metastatic HER2+ breast cancer setting. Spring mentions the HER2CLiMB-05 study evaluating tucatinib or placebo added to trastuzumab/pertuzumab maintenance therapy after taxane induction, with a secondary endpoint of CNS progression-free survival given tucatinib's good brain penetration. Bhave notes they have this trial open at their site, highlighting tucatinib's tolerability and CNS penetration, with the goal of preventing brain metastases by using it upfront with trastuzumab/pertuzumab.

Bhave then brings up the DESTINY-Breast09 trial looking at adding the antibody-drug conjugate trastuzumab deruxtecan to taxane/trastuzumab/pertuzumab in the first-line setting, given the impressive activity seen with these agents.

They discuss the potential challenges of giving more intensive regimens like adding an ADC upfront when some patients can have very durable responses to standard taxane/trastuzumab/pertuzumab alone, especially those with de novo HER2+ disease versus more heterogeneous tumors.

Spring and Bhave talk about treatment duration with the taxane component before moving to trastuzumab/pertuzumab maintenance. Both typically follow the 6 cycles used in CLEOPATRA, though sometimes stop taxanes earlier if there is an excellent response but toxicity or extend a few more cycles in robust patients seeking greater response.

This summary was AI-generated and edited for clarity.