Purpose The HER2CLIMB-05 study ( ClinicalTrials.gov identifier: NCT05132582 ) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). Patients and Methods Patients with centrally confirmed HER2+ MBC without evidence of progression post-induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo BID combined with trastuzumab/pertuzumab. Primary endpoint is investigator-assessed progression-free survival (PFS); secondary endpoints include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety. Results Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age: 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio = 0.641 95% CI: 0.514, 0.799; P < 0.0001; median PFS: 24.9 vs 16.3 months); a PFS benefit was seen regardless of presence/absence of BM or hormone receptor status. OS data remains immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (alanine aminotransferase: 28.2%; aspartate aminotransferase: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib due to TEAEs. Conclusions Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.
Dièras et al. (Wed,) studied this question.