Amol Akhade, Senior Consultant at Fortis Hospitals Mumbai, shared a post on LinkedIn:
“HER2CLIMB-05: Redefining the Frontline HER2+ Landscape
Pfizer’s HER2CLIMB-05 reports positive topline results – adding TUKYSA (tucatinib) to trastuzumab + pertuzumab maintenance significantly improved PFS in first-line HER2+ metastatic breast cancer (MBC).
This marks the first frontline advance since CLEOPATRA (2012).
Trial snapshot
Post-induction with taxane + HP → maintenance with either TUKYSA + HP or placebo + HP. Primary endpoint (PFS) met, with a clinically meaningful and statistically significant improvement. Tolerable safety, consistent with established standards.
The Context
Despite a decade of progress in HER2-targeted therapy, most patients still relapse within two years on HP maintenance. Tucatinib’s strong CNS activity and favorable tolerability make it an appealing option early in the course of disease.
What Oncologists Are Discussing
Across global and Indian expert groups, including our Breast Oncology Network, the discussion quickly turned to how this fits with DESTINY-Breast09 and PATINA data:
- “With DESTINY-09 PFS out and PATINA data considered, relevance depends on the PFS delta – perhaps more in HR-negative disease.”
- “Essentially 3 anti-HER2 vs 2 anti-HER2 + 1 anti-HER2 ADC.”
- “It will boil down to sequencing: T-DXd → TUKYSA + HP vs TUKYSA + HP → T-DXd.”
- “And the unanswered question – do we need to add pertuzumab to T-DXd?”
This perfectly summarizes where the field stands: not just which drug works, but in what order and for which biologic subset.
Implications
HER2CLIMB-05 may push tucatinib into routine first-line maintenance, but the sequencing with trastuzumab deruxtecan (T-DXd) will define real-world strategy.
Upcoming hashtag#SABCS25 presentations should clarify:
Median PFS and HR magnitude CNS-specific benefit Survival impact and crossover data
Bottom line:
Tucatinib + HP in maintenance may soon become the new foundation for HER2+ MBC, but the DESTINY-09 delta and sequencing data will decide how it coexists with T-DXd.”
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