Dataset Information

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.

ABSTRACT:

Background

The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.

Methods

All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services' (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model.

Results

64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5-16.5) vs. 31.0 for TBP (95% CI: 20.6-41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40-0.99, P = 0.045].

Conclusion

In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.

SUBMITTER: Hammerman A

PROVIDER: S-EPMC4574060 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.

Hammerman Ariel A Greenberg-Dotan Sari S Feldhamer Ilan I Bitterman Haim H Yerushalmi Rinat R

PloS one 20150916 9

<h4>Background</h4>The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.<h4>Methods</h4>All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit He ...[more]

PMID: 26375590

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Project description:Gene expression data of HER2+ breast tumor samples Increasing evidence indicates that a subset of patients with HER2-positive breast cancer may achieve significant clinical benefit with anti-HER2 targeted therapy without chemotherapy. Thus, identification of biomarkers of long-term benefit from anti-HER2 agents is needed, especially in the metastatic setting. In the HERLAP study (NCT00842998), patients with HER2-positive metastatic breast cancer were randomized to trastuzumab or lapatinib as first-line therapy. Patients showing radiological signs of tumor regression after 8 weeks of treatment were allowed to continue on single agent anti-HER2 therapy until disease progression. Chemotherapy was added to anti-HER-2 therapy in patients failing to achieve tumor regression at the 8-week evaluation and those progressing at any time. Expression analysis of 105 selected genes was performed from formalin-fixed paraffin-embedded in 17 primary tumor samples. The research-based PAM50 intrinsic subtypes were also identified. The association of the expression of each biomarker with clinical outcome endpoints was evaluated. Nineteen patients were enrolled. In 4 patients (21.1%) we observed disease control lasting longer than 12 months with single agent anti-HER2 therapy (range 14.9-38.8 months). High expression of 17q12-21 amplicon genes HER2 and GRB7, and the PAM50 HER2-enriched intrinsic profile, were found significantly associated with 8-week overall response rate and with the duration of disease control during single agent anti-HER2 therapy. Conversely, high expression of luminal-related genes such as PGR, MDM2 or PIK3CA, or the PAM50 luminal intrinsic profile, was found associated with reduced benefit from single agent anti-HER2 therapy. Conclusions: Our data indicate that gene expression-based biomarkers can identify patients with HER2-positive metastatic breast cancer that benefit substantially from single agent chemo-free anti-HER2 targeted therapy. In the study presented here, a well-defined cohort of 21 breast cancer cases from the HERLAP trial, was used to acquire expression profiles of a total of 105 unique genes

Dataset Information

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.

Background

Methods

Results

Conclusion

Publications

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.

Similar Datasets

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