American Association for Cancer Research
ccr-23-0117_supplementary_table_s2_suppts2.pdf (52.21 kB)

Supplementary Table S2 from Safety and Efficacy of Tucatinib, Letrozole, and Palbociclib in Patients with Previously Treated HR+/HER2+ Breast Cancer

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posted on 2023-07-14, 13:20 authored by Elena Shagisultanova, William Gradishar, Ursa Brown-Glaberman, Pavani Chalasani, Andrew J. Brenner, Alison Stopeck, Hannah Parris, Dexiang Gao, Tessa McSpadden, Jose Mayordomo, Jennifer R. Diamond, Peter Kabos, Virginia F. Borges

Serious adverse events



To overcome resistance to antihormonal and HER2-targeted agents mediated by cyclin D1-CDK4/6 complex, we proposed an oral combination of the HER2 inhibitor tucatinib, aromatase inhibitor letrozole, and CDK4/6 inhibitor palbociclib (TLP combination) for treatment of HR+/HER2+ metastatic breast cancer (MBC). Phase Ib/II TLP trial (NCT03054363) enrolled patients with HR+/HER2+ MBC treated with ≥2 HER2-targeted agents. The phase Ib primary endpoint was safety of the regimen evaluated by NCI CTCAE version 4.3. The phase II primary endpoint was efficacy by median progression-free survival (mPFS). Forty-two women ages 22 to 81 years were enrolled. Patients received a median of two lines of therapy in the metastatic setting, 71.4% had visceral disease, 35.7% had CNS disease. The most common treatment-emergent adverse events (AE) of grade ≥3 were neutropenia (64.3%), leukopenia (23.8%), diarrhea (19.0%), and fatigue (14.3%). Tucatinib increased AUC10–19 hours of palbociclib 1.7-fold, requiring palbociclib dose reduction from 125 to 75 mg daily. In 40 response-evaluable patients, mPFS was 8.4 months, with similar mPFS in non-CNS and CNS cohorts (10.0 months vs. 8.2 months; P = 0.9). Overall response rate was 44.5%, median duration of response was 13.9 months, and clinical benefit rate was 70.4%; 60% of patients were on treatment for ≥6 months, 25% for ≥1 year, and 10% for ≥2 years. In the CNS cohort, 26.6% of patients remained on study for ≥1 year. TLP combination was safe and tolerable. AEs were expected and manageable with supportive therapy and dose reductions. TLP showed excellent efficacy for an all-oral chemotherapy-free regimen warranting further testing.See related article by xxxx, p. xxxx

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