The phase 3 HER2CLIMB-05 trial will investigate tucatinib plus standard of care maintenance in the first-line setting for patients with HER2-positive metastatic breast cancer.
Tucatinib (Tukysa) plus first-line standard of care (SOC) maintenance therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta) will be examined for its ability to prolong progression-free survival (PFS) and maintain health-related quality of life (HRQOL) in patients with HER2-positive metastatic breast cancer in the ongoing phase 3 HER2CLIMB-05 trial (NCT05132582).
Details of the trial were presented in a poster at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
Other goals of this study include evaluating antitumor activity, overall survival, and safety and tolerability of the treatment combination.
“The addition of tucatinib to first-line [standard of care] maintenance therapy with trastuzumab and pertuzumab may extend PFS while maintaining QOL. In patients with brain metastases, tucatinib had demonstrated the ability to improve PFS, OS, and/or delay the emergence of brain metastases; therefore, it is thought that patients in the first-line setting may also benefit from receiving tucatinib,” study authors who were led by Erika Hamilton, MD, director of Breast Cancer and Gynecologic Research Program at Sarah Cannon Research Institute at Tennessee Oncology in Nashville, Tennessee, wrote in their poster.
To enroll, patients must have centrally confirmed HER2-positive breast carcinoma, unresectable locally advanced or metastatic disease, and received 4 to 8 cycles of previous treatment with trastuzumab and pertuzumab in the first-line setting with no evidence of disease progression. Additional criteria include having known hormone receptor status, an ECOG performance status of 0 or 1, and either no evidence of brain metastases, untreated brain metastases that are asymptomatic without evidence of progression, or previously treated brain metastases that are asymptomatic and haven’t progressed since treatment.
Exclusion criteria consisted of having prior treatment with any anti-HER2 and/or anti-EGFR tyrosine kinase inhibitors and an inability to undergo contrast MRI of the brain. Central nervous system exclusion criteria consisted of having symptomatic brain metastases, brain metastases with progression since beginning frontline treatment, and ongoing use of corticosteroids with a daily dose of more than 2 mg of dexamethasone.
About 650 patients will be randomized 1:1 following 4 to 8 cycles of complete induction with trastuzumab/pertuzumab and taxane therapy to receive oral tucatinib at 300 mg twice daily or matched placebo plus continuous trastuzumab/pertuzumab. In place of trastuzumab and pertuzumab individually, patients may also receive subcutaneous pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo).
The time to deterioration of HRQOL is defined as the time to 10-point decrease in the global health status/QOL scale by the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). While evaluating safety, investigators will look at adverse effects, clinical laboratory assessments, and the frequency of dose holds, dose reductions, and treatment discontinuation.
Exploratory objectives outlined in the presentation include the identification of somatic alterations associated with resistance to tucatinib, evaluation of health utilities by the EuroQol-5 Dimension 5 Level (EQ-5D-5L) questionnaire, and evaluation of global health status and physical and role functional scales of EORTC QLQ-C30.
Hamilton EP, O’Sullivan C, Martin M, et al. Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (HER2CLIMB-05, trial in progress). J Clin Oncol. 2022;40(suppl 16):TPS1108. doi: 10.1200/JCO.2022.40.16_suppl.TPS1108