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Observational Study
. 2019 Oct;51(4):1527-1539.
doi: 10.4143/crt.2018.598. Epub 2019 Jun 4.

BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy

Sung-Bae Kim  1 , In-Gu Do  2 , Janice Tsang  3 , Tae-You Kim  4 , Yoon-Sim Yap  5 , Gerardo Cornelio  6 , Gyungyub Gong  7 , Soonmyung Paik  8 , Suee Lee  9 , Ting-Ying Ng  10 , Sarah Park  11 , Ho-Suk Oh  12 , Joanne Chiu  3 , Joohyuk Sohn  13 , Moonhee Lee  14 , Young-Jin Choi  15 , Eun Mi Lee  16 , Kyong-Hwa Park  17 , Christos Nathaniel  18 , Jungsil Ro  19
Affiliations
Observational Study

BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy

Sung-Bae Kim et al. Cancer Res Treat. 2019 Oct.

Abstract

Purpose: BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents.

Materials and methods: Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.

Results: p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.

Conclusion: The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Keywords: Biomarkers; Breast neoplasms; HER2; Lapatinib; Trastuzumab.

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Conflict of interest statement

Sung-Bae Kim has received funding from Novartis, Sanofi Aventis, Kyowa Kirim Inc., Dongkook Pharmaceuticals Company Ltd. Gerardo Cornelio has received funding from Renovo; has served as a consultant/advisory role for Astra Zeneca Oncology, BF, MSD Oncology, and Esai Oncology. Yoon Sim Yap has served as a consultant/advisory role from Novartis. Soonmyung Paik has received funding from GSK for this study; has served as a consultant/advisory role for Leica Biosystems. Christos Nathaniel is an employee of Novartis Pharmaceuticals Corporation. The following authors have nothing to disclose: In-Gu Do, Janice Tsang, Tae-You Kim, Gyungyub Gong, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, and Jungsil Ro.

Figures

Fig. 1.
Fig. 1.
Progression-free survival (PFS) with lapatinib based regimens for all patients and biomarker subgroups. (A) All patients. (B) Patients with p95HER2 expression. (C) Patients with PTEN deletion/down-regulation. (D) Patients with PIK3CA mutation. Note: Log-rank test of survival distribution equality for subgroups was defined by positive and negative biomarker status. CI, confidence interval.
Fig. 2.
Fig. 2.
Progression-fee survival (PFS) with trastuzumab-based regimens for all patients and biomarker subgroups. (A) All patients. (B) Patients with p95HER2 expression. (C) Patients with PTEN deletion/down-regulation. (D) Patients with PIK3CA mutation. Note: Log-rank test of survival distribution equality for subgroups was defined by positive and negative biomarker status. CI, confidence interval.
Fig. 3.
Fig. 3.
Biomarker status for the three biomarkers, at primary diagnosis (A) and at recurrence/metastasis (B), for the analysis population.
Fig. 4.
Fig. 4.
Conversion/conservation of biomarker status.
See this image and copyright information in PMC

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