Do all patients with advanced HER2 positive breast cancer need upfront-chemo when receiving trastuzumab? Randomized phase III trial SAKK 22/99

Pagani, Olivia and Klingbiel, Dirk and Ruhstaller, Thomas and Nole, Franco and Eppenberger-Castori, Serenella and Oehlschlegel, Christian and Bernhard, Jürg and Brauchli, Peter and Hess, Dagmar and Mamot, Christoph and Munzone, Elisabetta and Pestalozzi, Bernhard C. and Rabaglio, Manuela and Aebi, Stefan and Ribi, Karin and Rochlitz, Christoph and Rothgiesser, Karin and Thürlimann, Beat and von Moos, Roger and Zaman, Khalil and Goldhirsch, Aron and Swiss Group for Clinical Cancer, Research. (2017) Do all patients with advanced HER2 positive breast cancer need upfront-chemo when receiving trastuzumab? Randomized phase III trial SAKK 22/99. Annals of Oncology, 28 (2). pp. 305-312.

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Official URL: https://edoc.unibas.ch/62417/

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Background: HER2-targeted therapy plus chemotherapy is standard treatment in advanced HER2+ breast cancer. Trastuzumab alone followed by addition of chemotherapy at disease progression versus upfront combination therapy has not been elucidated. Patients and methods: One-hundred seventy-five patients with measurable/evaluable HER2+ advanced disease without previous HER2-directed therapy were randomized to trastuzumab alone followed, at disease progression, by the combination with chemotherapy (Arm A) or upfront trastuzumab plus chemotherapy (Arm B). Chemotherapy could be stopped after </=6 cycles in responding patients, trastuzumab was continued until progression. The primary endpoint of this superiority trial was time to progression (TTP) on combined trastuzumab-chemotherapy (Combination-TTP) in both arms. Secondary endpoints included response rate, TTP, overall survival, quality of life and toxicity. Results: Combination-TTP was longer than expected in both arms, 12.2 months in Arm A and 10.3 months in Arm B and not significantly different (hazard ratio [HR] 0.7; 95% CI 0.5-1.1; P =0.1). Overall survival was also not significantly different (HR 0.9; 95% CI 0.6-1.5; P = 0.55). In Arm A, the median TTP before introduction of chemotherapy was 3.7 months (95% CI 2.3-5.4), yet at 2 years 6% of patients were still on trastuzumab alone. Patients without visceral disease had a Combination-TTP of 21.8 months in arm A, compared with 10.1 months in arm B (unplanned analysis HR 2.1, 95% CI 1.1-4.2, P = 0.03). Patients with visceral disease showed no difference. Toxicity was chemotherapy-related. Conclusion: The outcome of patients receiving sequential trastuzumab-chemotherapy or upfront combination was similar. We failed to demonstrate superiority of the sequential approach. These results nevertheless suggest chemotherapy and its toxicity can be deferred, especially in patients with indolent, non-visceral disease. Despite a larger non-inferiority confirmatory study would be needed, these findings represent an additional proof of concept that de-escalation strategies can be discussed in individual patients.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunology and Biology (Zippelius/Rochlitz)
UniBasel Contributors:Rochlitz, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Apr 2020 12:55
Deposited On:16 Apr 2020 12:55

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