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.

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.

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).

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.

Videos

Peter A. Kaufman, MD, reviews data in patients with HER2+ metastatic breast cancer treated with tucatinib-based therapy.

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

Peter A. Kaufman, MD, Associate Professor of Medicine at the Geisel School of Medicine at Dartmouth and the Norris Cotton Cancer Center in Lebanon, New Hampshire, discusses the side effect profiles of the microtubule inhibitor eribulin mesylate and the oral chemotherapeutic agent capecitabine.

In a phase III trial presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, eribulin did not to show a statistically significant survival benefit compared to capecitabine in patients with previously treated metastatic breast cancer.

Kaufman notes that there were also no definitive findings regarding which drug had a more tolerable side effect profile. This issue is common in metastatic breast cancer with other chemotherapeutic agents, Kaufman says. Patients in the eribulin arm of the study saw a higher incidence of peripheral neuropathy and neutropenia while those treated with capecitabine experienced adverse events of hand-foot syndrome, diarrhea, and nausea.

Peter A. Kaufman, MD, Associate Professor of Medicine at the Geisel School of Medicine at Dartmouth, discusses the side effect profiles of the microtubule inhibitor eribulin mesylate and the oral chemotherapeutic agent capecitabine.


Peter A. Kaufman, MD

Articles

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

Dr. Kaufman on Eribulin/ Capecitabine Side Effects