Tucatinib Combos Improves PFS in Breast Cancer Subset
December 10, 2025
2 min read
Key takeaways:
Table of Contents
- The tucatinib combination resulted in a 36% reduction in risk for disease progression or death.
- Median PFS was 24.9 months with tucatinib vs. 16.3 months with placebo.
SAN ANTONIO — The addition of tucatinib to first-line trastuzumab plus pertuzumab delayed disease progression among a cohort of women with HER2-positive metastatic breast cancer compared with standard of care, according to study findings.
Findings from the randomized, double-blind, phase 3 HER2CLIMB-05 trial, presented at San Antonio Breast Cancer Symposium, were simultaneously published in Journal of Clinical Oncology.
Erika
P.
Hamilton, MD,
shares findings from phase 3 HER2CLIMB-05 trial, during the San Antonio Breast Cancer Symposium.
Erika P. Hamilton
“The current standard of care for first-line treatment of HER2-positive metastatic breast cancer consists of induction therapy with taxane and dual anti-HER2 targeted antibodies, which is then typically followed by maintenance therapy with trastuzumab and pertuzumab alone. Despite this, most patients progress and unfortunately will not go on to receive second-line therapy,” Erika P. Hamilton, MD, director of breast cancer research at Sarah Cannon Research Institute, said during a press briefing.
“We initiated the HER2CLIMB-05 trial to investigate the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line maintenance therapy in [this patient population].”
Study protocol
Hamilton and colleagues enrolled 654 women (median age, 54 years; 45% white, 35.2% Asian, 19.3% Hispanic and 2.9% Black) with centrally confirmed HER2-positive metastatic breast cancerv with no evidence of progression after four to eight cycles of taxane in combination with trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech). Asymptomatic brain metastases were allowed.
Between March 2022 and July 2024, researchers randomly assigned women 1:1 to either tucatinib (Tukysa, Seagen) plus trastuzumab and pertuzumab (n = 326) or placebo plus continued trastuzumab and pertuzumab (n = 328). Patients with hormone receptor-positive tumors were permitted to take endocrine therapy during the maintenance phase.
Investigator-assessed PFS per RECIST v1.1 served as the primary endpoint. Secondary endpoints included OS, PFS by blinded independent central review, investigator-assessed central nervous system PFS and safety.
Treatment benefit
At median follow-up of 23 months, data showed the tucatinib regimen significantly improved investigator-assessed PFS, from 16.3 months in the placebo arm to 24.9 months with in the tucatinib arm (HR = 0.641; 95% CI, 0.514-0.799).
“PFS was consistent across all prespecified patient subgroups,” Hamilton said. “Patients received benefit with the addition of tucatinib regardless of whether they had de novo or recurrent disease.”
Researchers additionally observed an improvement in PFS among women with hormone receptor-negative disease, from 12.6 months with placebo to 24.9 months with tucatinib (HR = 0.554; 95% CI, 0.403-0.761).
“Similarly, for women with hormone receptor-positive disease, tucatinib benefited these patients,” Hamilton said. “PFS was lengthened from 18.1 months with placebo to up to 25 months with the addition of tucatinib.”
OS data were not yet reached, with the number of deaths observed to date of 51 in the tucatinib arm. Of note, 13.5% of patients in the tucatinib arm discontinued treatment due to treatment-emergent adverse events.
“The tucatinib combination showed a manageable safety profile, with diarrhea, nausea and elevated liver enzymes, mostly of low grade, being the most common adverse events,” Hamilton said.
Researchers acknowledged study limitations, including potential selection bias and that differences in brain imaging frequency and cessation of routine imaging after systemic progression may have affected the accuracy of central nervous system-PFS assessments.
“HER2CLIMB-05 has demonstrated that the addition of tucatinib to trastuzumab and pertuzumab represents an enhanced first-line therapy option for patients, providing an opportunity not only to prolong time to disease progression, but also providing an opportunity for these patients to have an increased amount of time off chemotherapy,” Hamilton said.
Sources/Disclosures
Source:
Hamilton EP, et al. Abstract GS1-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 9-12, 2025; San Antonio.
Disclosures:
Seagen funded this study. Hamilton reports consulting/advisory roles with AstraZeneca, Daiichi Sankyo, Eli Lilly & Co., Genentech/Roche, Gilead Sciences, Jazz Pharmaceuticals, Novartis, Pfizer and several other companies; and research funding from AbbVie, Arvinas, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squib, Daiichi Sankyo, Genentech/Roche, Gilead Sciences, Incyte, Novartis, Seagen and several other companies. Please see the study for all other authors’ relevant financial disclosures.
Ask a clinical question and tap into Healio AI’s knowledge base.
- PubMed, enrolling/recruiting trials, guidelines
- Clinical Guidance, Healio CME, FDA news
- Healio’s exclusive daily news coverage of clinical data