Patient Characteristics, Treatment Patterns, and Clinical Outcomes Associated With Tucatinib Therapy in HER2+ Metastatic Breast Cancer

Background

• Tucatinib is an oral tyrosine kinase inhibitor approved in multiple countries in combination with trastuzumab and capecitabine for adult patients with human epidermal growth factor 2 (HER2)+ metastatic breast cancer (MBC), including patients with brain metastases, who have received ≥1 prior anti-HER2–based regimens in the metastatic setting.
• In HER2CLIMB, a phase 2, randomized, placebo-controlled trial, tucatinib in combination with trastuzumab and capecitabine demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) with a tolerable safety profile in 612 patients with HER2+ MBC (including those with previously untreated, treated and stable, or treated and progressing brain metastases).
  • For patients receiving tucatinib, trastuzumab, and capecitabine, median OS was 21.9 (95% CI: 18.3–31.0) months and 12-month survival probability was 75.5% (95% CI: 70.4–70.9).
  • Median progression-free survival (PFS) was 7.8 (95% CI: 7.5–9.6) months; the proportion (95% CI) of patients who had not progressed at 6 and 12 months was 62.9% (56.9–68.4) and 33.1% (26.6–39.7), respectively.

Methods

• This retrospective cohort study included patients with HER2+ MBC diagnosed with metastatic disease between January 2017 and July 2022 in the nationwide de-identified electronic health record–derived Flatiron Health Metastatic Breast Cancer database. Data were collected from patients who received tucatinib-based treatment outside of a clinical trial setting.
• Demographic and clinical characteristics of patients were described during the baseline period prior to tucatinib initiation.
• Key outcomes were measured from the initiation of tucatinib therapy and included median OS (OS), median time to next treatment (TTNT) as a proxy for PFS6, median time to discontinuation (TTD), and persistence rates (proportion of patients remaining on therapy at 9, 12, and 18 months).
  • Time-to-event analyses were conducted using Kaplan-Meier methodology to account for censoring.

Results

• Compared with the HER2CLIMB trial population, a higher proportion of patients in this study had brain metastases pre-tucatinib treatment. Patients in this study also had poorer performance status, greater racial diversity, and fewer prior lines of therapy compared with those in the HER2CLIMB trial.
• Median (interquartile range, IQR) lines of prior therapy were 2 (1–3) among all patients and 1 (1–3) and 3 (2–4) among patients with and without brain metastases pre-tucatinib, respectively, indicating a trend of earlier use of tucatinib-based treatment among patients with brain metastases vs those without brain metastases.
• Of the 48 patients who didn’t receive tucatinib, trastuzumab, plus capecitabine, 20 (42%) patients received tucatinib with trastuzumab, 14 (29%) tucatinib with capecitabine, 7 (15%) tucatinib monotherapy, and 7 (15%) other tucatinib combinations.
• Median OS (95% CI) was 26.1 (20.2–not reached [NR]) months from initiation of tucatinib treatment. Six- and 12-month survival probability (95% CI) were 86.1% (81.0–91.6), and 74.2% (67.3–81.9), respectively.
• In 2L and 3L, 12-month survival probability (95% CI) was 84.1% (75.6–93.5) for patients receiving any tucatinib regimen and 83.5% (73.3–95.2) for patients receiving the FDA-labeled tucatinib triplet combination.
• Median (95% CI) TTD was 8.1 (5.7–9.5) months in the overall population and slightly longer in patients receiving tucatinib in 2L or 3L.
• For patients who received tucatinib immediately following T-DXd (n=29), median OS (95% CI) was 12.6 (11.9–NR) months, with a 12-month survival probability (95% CI) of 61.8% (43.2–88.5).

Conclusions

• The majority (71%) of patients receiving tucatinib-based treatment in clinical practice in the US have brain metastases at treatment initiations. This percentage constitutes a larger proportion of the treated population than in HER2CLIMB (~48% of patients).
• In real-world practice, tucatinib-based treatment was initiated sooner, as an earlier line of therapy, in patients with brain metastases than in those without brain metastases.
• While the populations aren’t directly comparable, tucatinib-based treatment in the real-world setting is associated with a similar median OS, median TTNT (as a proxy for PFS),6 and median TTD as observed in HER2CLIMB, reinforcing its durable efficacy in patients with HER2+ MBC with and without brain metastases.
• A potential benefit in OS, TTNT, and TTD was also observed in a subgroup of patients who received tucatinib following T-DXd.

Kaufman PA, Neuberger E, Hsu LI et al. Patient Characteristics, Treatment Patterns, and Clinical Outcomes Associated With Tucatinib Therapy in HER2+ Metastatic Breast Cancer. Abstract presented at: 2022 San Antonio Breast Cancer Symposium, December 6-10, 2022.