What happens when MD Anderson’s translational firebrand Jason Mouabbi sticks a microphone in front of long-time HER2 guru Mothaffar Rimawi just days after the first read-out of DESTINY-Breast09? In sixty candid minutes they chart how trastuzumab deruxtecan (T-DXd) ± pertuzumab vaulted past CLEOPATRA; posting a headline 41-month PFS that forces oncologists to rethink induction/maintenance dogma, sequencing, and even the forbidden word “cure.” in what was previously considered uncurable. Along the way they debate ILD fears, whether any patient should ever leave the clinic without concurrent endocrine therapy, and christen T-DXd as “the great equalizer” for tumors burdened by ESR1, PIK3CA or BRCA mutations. By the end, Dr. Rimawi’s motto “put your best player in at kickoff” feels less like a bravado and more like the tomorrow’s standard of care.

Why you’ll want to listen

• Design matters: how DB-09’s two experimental arms (T-DXd alone vs T-DXd + pertuzumab) were built to settle the dual-blockade question once and for all.

• A 41-month shockwave: the largest PFS ever seen in metastatic HER2-positive breast cancer—and why it may still climb.

• Induction vs “until further notice”: can oncologists still offer a chemo-free maintenance phase, or does the ADC stay on forever?

• ILD in real life: 12 % remains, but community doctors already trade scheduled breaks for lower risk without sacrificing depth of response.

• Sequencing after an early ADC: if T-DXd moves up front, what’s left for tucatinib, T-DM1 or neratinib and more importnatly does it matter?

• Cure? Dare we say it: Rimawi argues we are “closest in any solid tumor” to normal life expectancy; Dr. Mouabbi pushes him to define what bold looks like.

• Endocrine cross-talk—still ignored: fewer than 10 % of DB-09 patients got concomitant endocrine therapy despite 60 % ER-positivity, a missed chance the speakers vow to fix.

• PI3K mutation? Payload doesn’t care: why the ADC’s topoisomerase warhead levels the playing field across resistance genotypes.

🎧 Like, share, and subscribe for more CHM Conversations that turn headline data into bedside decisions.

#BreastCancer #HER2Positive #TDXd #DESTINYBreast09 #OncologyPodcast #PrecisionMedicine #CHMConversations

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