The following article features coverage from the 2019 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

For previously treated patients with metastatic HER2-positive breast cancer — including those with brain metastases — the addition of tyrosine kinase inhibitor tucatinib to capecitabine and trastuzumab improved progression-free survival (PFS) and overall survival (OS), according to the primary results of the phase 2 HER2CLIMB trial (ClinicalTrials.gov Identifier: NCT02614794). The trial results were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in the New England Journal of Medicine.1,2

From 155 sites in 15 countries, 612 patients were enrolled with locally advanced or metastatic HER2-positive breast cancer. All patients had prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1), and patients with newly diagnosed, progressing, or stable brain metastases were eligible for the trial.

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“HER2CLIMB is the first randomized trial to include patients with untreated and progressing brain metastases,” said study presenter Rashmi K. Murthy, MD, assistant professor of breast medical oncology, The University of Texas MD Anderson Cancer Center, Houston.

Patients were randomly assigned to receive combination therapy with tucatinib, capecitabine, and trastuzumab (410 patients); or placebo, capecitabine, and trastuzumab (202 patients).


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Overall, the study met its primary end point, showing that among the first 480 patients enrolled in the trial, those on the tucatinib arm had a 46% lower likelihood of disease progression or death compared with patients on the placebo arm (hazard ratio [HR], 0.54; 95% CI, 0.42-0.71); P <.00001). Patients on the tucatinib arm had a PFS benefit of 2.2 months compared with the placebo arm (7.8 vs 5.6 months, respectively).

Patients in the tucatinib cohort also had 34% lower likelihood of death (HR, 0.66; 95% CI, 0.50-0.88; P =.0048) and a median OS gain of 4.5 months compared with the placebo arm (21.9 vs 17.4 months, respectively).

In addition, the confirmed objective response rate was higher among patients in the tucatinib arm compared with the placebo arm (41% vs 23%, respectively; P =.00008).

For patients with brain metastases, a 52% lower likelihood of disease progression or death was seen among those who received tucatinib compared with placebo (HR, 0.48; 95% CI, 0.34-0.69); P <.00001).

The most common adverse events were diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting for patients on the tucatinib arm. According to Dr Murthy, all were “mostly low grade.”

A higher frequency of grade 3 or higher diarrhea, palmar-plantar erythrodysesthesia syndrome, and increased liver enzymes were seen in the tucatinib arm.

A new drug application, or NDA, for the triplet combination is anticipated to be submitted to the US Food and Drug Administration in early 2020.3

Disclosure: The study was sponsored by Seattle Genetics, Inc. Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of SABCS by visiting the conference page.

References

  1. Murthy R, Loi S, Okines A, et al. Tucatinib vs placebo, both combined with capecitabine and trastuzumab, for patients with pretreated HER2-positive metastatic breast cancer with and without brain metastases (HER2CLIMB). Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS1-01.
  2. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer . N Engl J Med. doi: 10.1056/NEJMoa1914609.
  3. Adding tucatinib to drug combination extends survival for advanced HER2+ breast cancer patients [news release]. San Antonio, TX: MD Anderson Cancer Center; December 11, 2019. Accessed December 11, 2019.