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Dual HER-2 therapy with trastuzumab, lapatinib improves EFS
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SAN ANTONIO — The addition of lapatinib to trastuzumab with taxane therapy improved EFS among a cohort of patients with HER-2-positive breast cancer, according to results of a randomized phase 3 trial presented at the San Antonio Breast Cancer Symposium.
Ian E. Krop , MD, PhD, assistant professor of medicine at Harvard Medical School and instructor in medicine, adult oncology at Dana-Farber Cancer Institute, and colleagues aimed to investigate 16 weeks of dual therapy with trastuzumab (Herceptin, Genentech) and lapatinib (Tykerb, Novartis) with paclitaxel on pathologic complete response in a cohort of 305 patients with HER-2-positive disease.
However, researchers previously found that pathologic complete response did not increase significantly with dual therapy. In this secondary analysis, they evaluated the effects of the combination overall and in gene expression-defined subgroups on EFS.
“There are substantial data to suggest synergy between the combination of trastuzumab and lapatinib,” Krop said during his presentation. “This combination is active in first-line and pretreated metastatic HER-2-positive disease. The addition of lapatinib is associated with an increase in pathologic complete response.”
Krop noted, however, that key studies have also shown that this combination failed to improve EFS or OS.
“In an effort to try to understand these contradictory results in these trials, and to understand the subset of HER-2-positive patients who may benefit, we undertook this study,” he said.
The current analysis included 104 patients treated with the dual regimen of trastuzumab-lapatinib with paclitaxel, 103 treated with trastuzumab and paclitaxel, and 58 treated with lapatinib-paclitaxel. However, the latter arm closed early due to futility observed in other trials.
Eligible participants had stage II to III disease and underwent biopsy.
Thirty-nine EFS events occurred over a median follow-up of 5.4 years.
With trastuzumab and paclitaxel as the reference, results showed a benefit with the addition of lapatinib to trastuzumab (HR = 0.35; 95% CI, 0.15-0.83). There was no benefit for paclitaxel-lapatinib (HR = 1.24; 95% CI, 0.61-2.51).
“In this study, we did demonstrate an improvement in EFS comparing the trastuzumab-lapatinib arm to trastuzumab and paclitaxel,” he said. He added that this benefit appeared particularly pronounced in the hormone receptor-negative subset (HR = 0.12).
The addition of lapatinib to the trastuzumab and paclitaxel regimen also yielded an improvement in OS (HR = 0.22).
In an analysis based on pathologic complete response status, results indicated that responding patients had better EFS improvements than patients without a pathologic complete response (HR = 0.34; 95% CI, 0.16-0.72).
The researchers also conducted an exploratory analysis that included patients with luminal A and B disease, along with those with HER-2-enriched disease.
“The prognostic effect of pathologic complete response was relatively modest in the luminal A and luminal B subtypes,” Krop said. “In the HER-2-enriched subtype, there was quite a marked effect.”
Those in the HER-2-enriched group who achieved a pathologic complete response had a strong EFS benefit, whereas those who did not were increasingly likely to recur, according to Krop.
“The addition of lapatinib to a trastuzumab/taxane regimen was associated with a significant improvement in EFS,” Krop concluded. “Consistent with other studies, pathologic complete response was associated with favorable long-term outcome.”
He also noted that immune activation by RNA was an independent predictor of favorable EFS.
“These data are hypothesis-generating and require validation,” Krop said. – by Rob Volansky
Reference:
Krop IE, et al. Abstract GS3-02. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: Krop reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.