Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data

Sabine Schmid, Dirk Klingbiel, Stefan Aebi, Aron Goldhirsch, Christoph Mamot, Elisabetta Munzone, Franco Nolè, Christian Oehlschlegel, Olivia Pagani, Bernhard Pestalozzi, Christoph Rochlitz, Beat Thürlimann, Roger von Moos, Patrik Weder, Khalil Zaman, Thomas Ruhstaller, Sabine Schmid, Dirk Klingbiel, Stefan Aebi, Aron Goldhirsch, Christoph Mamot, Elisabetta Munzone, Franco Nolè, Christian Oehlschlegel, Olivia Pagani, Bernhard Pestalozzi, Christoph Rochlitz, Beat Thürlimann, Roger von Moos, Patrik Weder, Khalil Zaman, Thomas Ruhstaller

Abstract

Background: The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response.

Methods: This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed.

Results: Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31-72) and of 18% (95%CI 10-30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit.

Conclusion: Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies.

Trial registration: NCT00004935 ; first posted 27.01.2003, retrospectively registered.

Keywords: HER-positive breast cancer; Long-term responders; Trastuzumab monotherapy.

Conflict of interest statement

The authors have declared the following competing interest:

  1. Sabine Schmid: Advisory Board (institutional): MSD, Boehringer Ingelheim; Travel Grants: Boehringer Ingelheim, Takeda, MSD

  2. Dirk Klingbiel: After after having completed the analysis (being employed by the Swiss Group for Clinical Cancer Research, Coordinating Center), but before submission of the manuscript has moved to F. Hoffmann-La Roche Ltd.

  3. Stefan Aebi: Advisory Board (institutional): Pfizer, Roche

  4. Elisabetta Munzone: Advisory board: Pierre Fabre, Genomic Health

  5. Christoph Rochlitz: Hoffmann-La Roche: Travel and Accommodation Support and Advisory Role

  6. Beat Thürlimann: Personal Fees: Roche, AstraZeneca, Pfizer, Amgen, Eli Lilly; Stock ownership: Novartis, Roche

  7. Roger von Moos: Advisory board: Amgen, Roche, Pfizer, Novartis, BMS, Merck

  8. Khalil Zaman: Advisory board: Novartis, Roche, Amgen, Celgene, AstraZeneca, Pfizer, Lilly; Support for travel/participation to international congresses: Roche, Celgene, AstraZeneca, Pfizer, Lilly; Unrestricted support for the organization of multisponsored academic symposium from Roche

  9. Thomas Ruhstaller: Advisory Board: Novartis, Roche, Astra-Zeneca, Lilly; Travel Grants: Roche, Pfizer, Amgen; Honoraria: Pfizer. Thomas Ruhstaller is also a member of the editorial board (Associate Editor) in BMC Cancer.

Figures

Fig. 1
Fig. 1
Flow-Chart
Fig. 2
Fig. 2
OS of long-term versus short-term responders
Fig. 3
Fig. 3
Patterns of care of long-term responders including follow-up treatment

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Source: PubMed

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