1L HER2+ mBC maintenance - Seagen/Pfizer
Explore Trial Data
Top 10 by impressions - click to view on X
Among pts with ER+/HER2+ MBC, maintenance HP (control arm) had a PFS of: -29.1 mo in PATINA -16.3 mo in HER2CLIMB-05 The difference? In PATINA all pts also received ET (only 45% in...
T-DXd + pertuzumab approved for 1st L HER-2+ #bcsm! Now for the debates around induction length, maintenance, re-induction etc. My opinion: I'll induce to...
Nice table to put this rapidly evolving field in perspective #SABCS25
#SABCS25 ⏳️ After nearly a decade of therapeutic stagnation in the first-line treatment of HER2-positive breast cancer since the publication of CLEOPATRA, we suddenly find ourselves...
Adding tucatinib to standard maintenance therapy led to progression-free survival of more than two years in patients with HER2-positive metastatic breast cancer, according to results of the...
A new chemo free maintenance option for patients with HR+ & HR- HER-2 + disease in the 1st line setting post induction chemo that can provide a meaningful benefit in excess of 2 years is a...
DB-09, PATINA, HER2CLIMB-05. After been using the same 1L HER2+ MBC regimen for a decade, everything has changed within 1 single year. All guidelines to be rewritten, algorithms to be developed,...
HER2CLIMB-05 shows addition of tucatinib to maintenance HP, after median 6 cycles THP, improved mPFS 8.6 mos to 24.9 mos. Benefit more pronounced in HR-, but HR+ benefits as well....
#SABCS25 @ErikaHamilton9 presents HER2Climb05. Tucatinib prolonged PFS added to HP maintenance for HER2+ MBC. <50% of HR+ got ET! Why?? More toxicity but manageable....
#SABCS25 Recap #1 | HER2CLIMB-05 HER2CLIMB-05 showed that adding #tucatinib to maintenance HP after 4–6 cycles of THP improved mPFS to ~24 months...
HER2CLIMB-05 is a Phase III, randomized, double-blind, placebo-controlled trial evaluating the addition of tucatinib (Tukysa) to trastuzumab and pertuzumab as first-line maintenance therapy in patients with HER2-positive metastatic breast cancer. The trial enrolled 654 patients who had completed 4-8 cycles of taxane-based induction chemotherapy with trastuzumab and pertuzumab without disease progression. HER2CLIMB-05 demonstrated that adding a selective HER2 tyrosine kinase inhibitor to dual antibody maintenance significantly prolongs time off chemotherapy, representing the first positive Phase III trial of enhanced first-line maintenance in HER2+ mBC.
Phase III, international, randomized (1:1), double-blind, placebo-controlled trial (NCT05132582). Patients received tucatinib 300 mg orally twice daily or placebo alongside trastuzumab plus pertuzumab every 21 days. Endocrine therapy was permitted for HR-positive tumors. Stratified by disease status (de novo vs. recurrent), hormone receptor status, and brain metastases.
Adults with centrally confirmed HER2-positive metastatic breast cancer, ECOG PS 0-1, who had no disease progression after 4-8 cycles of first-line taxane-based induction with trastuzumab and pertuzumab. Patients with asymptomatic brain metastases were allowed; 12.2% had baseline brain metastases. Median age 54 years.
Tucatinib 300 mg orally twice daily plus trastuzumab and pertuzumab (HP) every 21 days versus placebo plus HP, administered as maintenance therapy until disease progression or unacceptable toxicity.
Primary endpoint: investigator-assessed progression-free survival (PFS) per RECIST 1.1. Key secondary endpoints: overall survival (OS), BICR-assessed PFS, CNS-PFS, safety, health-related quality of life, and pharmacokinetics.
At a median follow-up of 23 months, tucatinib plus HP significantly improved PFS versus placebo plus HP. Median PFS was 24.9 months (95% CI: 21.3-NR) versus 16.3 months (95% CI: 12.6-18.7), representing an absolute improvement of 8.6 months (HR 0.641; 95% CI: 0.514-0.799; p<0.0001). BICR-assessed PFS confirmed the benefit: 28.9 months versus 16.0 months (HR 0.654). In HR-negative patients, PFS HR was 0.554 (24.9 vs. 12.6 months). In HR-positive patients, PFS HR was 0.725 (25.0 vs. 18.1 months). Among patients with baseline brain metastases, median CNS-PFS nearly doubled from 4.3 to 8.5 months.
Overall survival data were immature at the time of analysis, with only 20% of required events (51 deaths) having occurred. Despite this, a positive numerical trend favoring tucatinib was observed: OS HR 0.539 (95% CI: 0.303-0.957; p=0.0320). Median OS was not reached in either arm.
The tucatinib and HP combination showed a manageable safety profile. Grade 3+ TEAEs occurred in 42-43% of tucatinib patients versus 24% with placebo. The most common AEs were diarrhea (72.7% vs. 51% any-grade, mostly low-grade), nausea, and elevated liver enzymes. Grade 3+ ALT elevation occurred in 13.5% and AST in 7.1%, generally asymptomatic and reversible. Hepatic events were the leading cause of tucatinib discontinuation (7.7%). Overall discontinuation of tucatinib due to AEs was 13.5% versus 2.2% for placebo. Dose modifications were required in 55.8% versus 34.6%.
HER2CLIMB-05 establishes tucatinib plus HP as a new enhanced first-line maintenance option for HER2+ mBC, offering patients over 2 years of chemotherapy-free disease control. The trial is notable for consistent benefit across HR subgroups and in patients with brain metastases. Key clinical questions include how this regimen compares or sequences with the newly approved DESTINY-Breast09 (T-DXd + pertuzumab) regimen, and whether OS benefit will be confirmed with further follow-up. Regulatory submissions are anticipated based on these data.
