Superimposable outcomes for sequential and concomitant administration of adjuvant trastuzumab in HER2-positive breast cancer: Results from the SIGNAL/PHARE prospective cohort

Background

Several adjuvant clinical trials in early HER2 positive breast cancer have assessed either sequential or concomitant incorporation of trastuzumab with chemotherapy. Only the NCCTG-N9831 trial prospectively compared the two modalities and whether their results didn't demonstrate a statistical significant difference, the authors have recommended the concurrent regimen with taxane chemotherapy instead of the sequential modality on the basis of a positive risk-benefit ratio. This present research assessed those two modalities sequential versus concomitant in the PHARE/SIGNAL cohort.

Methods

PHARE was a randomized phase III clinical trial (NCT00381901) and SIGNAL (RECF1098) was a prospective study specifically designed for GWAS analyses. The comparison in the HER2-positive group of adjuvant trastuzumab and chemotherapy modalities was based on a propensity score methodology applying the inverse probability of treatment weighting method (IPTW) in the cox regression model. Overall Survival (OS) and Disease Free Survival (DFS) were estimated using the Kaplan-Meier method and comparisons between groups were based on the log rank test.

Results

The SIGNAL/PHARE cohort included 11,728 breast cancer cases; 5,502 of them with HER2-positive tumour: 34.5% (1897/5502) were treated by sequential and 65.5% (3605/5502) by concomitant modality of administration for taxane-chemotherapy and trastuzumab. The adjusted comparison found similar OS (HR = 1.01; 95% CI: 0.86-1.19) and similar DFS (HR = 1.08; 95%CI 0.96-1.21).

Conclusions

These results suggest that the sequential administration of trastuzumab given after the completion of adjuvant chemotherapy might be as valid as the concomitant administration of trastuzumab and taxane chemotherapy in the adjuvant setting.

Clinical trial identification

NCT00381901 & RECF1098

Legal entity responsible for the study

French national Cancer Institute (INCa)

Funding

French national Cancer Institute (INCa)

Disclosure

X. Pivot: Honorarium for consultant with Roche, Novartis. J.Y. Pierga: Research funding from Roche.

S. Delaloge, T. Bachelot, J.P. Jacquin, G. Romieu, J. Gligorov: Consultant with honorarium from Roche

P. Fumoleau: Honorariums from Roche, GSK, Avenues, Johnson&Johnson. P. Kerbrat: honorarium from Roche. All other authors have declared no conflicts of interest.