Header

UZH-Logo

Maintenance Infos

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


Pagani, O; Klingbiel, D; Ruhstaller, T; Nolè, F; Eppenberger, S; Oehlschlegel, C; Bernhard, J; Brauchli, P; Hess, D; Mamot, C; Munzone, E; Pestalozzi, B; Rabaglio, M; Aebi, S; Ribi, K; Rochlitz, C; Rothgiesser, K; Thürlimann, B; Moos, R von; Zaman, K; Goldhirsch, A; Swiss Group for Clinical Cancer Research (SAKK) (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):305-312.

Abstract

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 methodsOne-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 trastuzumabchemotherapy (Combination-TTP) in both arms. Secondary endpoints included response rate, TTP, overall survival, quality of life and toxicity.ResultsCombination-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 two 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.ConclusionThe 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.

Abstract

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 methodsOne-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 trastuzumabchemotherapy (Combination-TTP) in both arms. Secondary endpoints included response rate, TTP, overall survival, quality of life and toxicity.ResultsCombination-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 two 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.ConclusionThe 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.

Statistics

Altmetrics

Downloads

0 downloads since deposited on 13 Jan 2017
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 February 2017
Deposited On:13 Jan 2017 11:12
Last Modified:21 Apr 2017 01:01
Publisher:Oxford University Press
ISSN:0923-7534
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Annals of Oncology following peer review. The definitive publisher-authenticated version Pagani O et al: Ann Oncol (2016) mdw622. DOI: https://doi.org/10.1093/annonc/mdw622 is available online at: https://doi.org/10.1093/annonc/mdw622.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/annonc/mdw622
PubMed ID:27998961

Download

Preview Icon on Download
Content: Accepted Version
Filetype: PDF - Registered users only until 20 December 2017
Size: 652kB
View at publisher
Embargo till: 2017-12-20