267P - Can contemporary trials in HER2-negative metastatic breast cancer (mBC) detect overall survival (OS) benefit?

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Breast Cancer
Presenter Sherko Kümmel
Citation Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365
Authors S. Kümmel1, C. Jackisch2, V. Müller3, A. Schneeweiss4, S. Klawitter5, M.P. Lux6
  • 1Cancer Center Essen, Klinikum Essen Mitte, 45136 - Essen/DE
  • 2Obstetrics And Gynecology, Sana Clinic Offenbach, Offenbach/DE
  • 3Department Of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg/DE
  • 4Division Gynecologic Oncology, National Center for Tumor Diseases (NTC) University Hospital, Heidelberg/DE
  • 5Biostatistics And Epidemiology, Roche Pharma AG, Grenzach Wyhlen/DE
  • 6Obgyn-department, University Breast Center Franconia, University Hospital Erlangen, Erlangen/DE



Although several recent trials have demonstrated improved progression-free survival (PFS) or time to progression (TTP) with first-line regimens for HER2-negative mBC, OS benefit is often elusive. We calculated required sample sizes to power for OS based on published data in recent trials.


Randomised superiority trials of first-line chemotherapy or targeted therapy for HER2-negative mBC including >150 patients, meeting the primary efficacy objective and published between 2000 and 2014 were identified. The sample sizes required to power for PFS (or TTP) and OS were calculated retrospectively for each trial using the observed results and study/recruitment follow-up durations (alpha=0.05, 2-sided log-rank test, 80% power), and summarised as a factor relative to the actual sample size (x  1 required x-fold more cases).


Only 8 of the 14 identified trials reported all information required for retrospective sample size calculation (Table). Most would have required a far larger sample size to demonstrate an OS gain (x: 0.5–2479) with the observed results. In 10 of 13 trials, the sample size required to power for OS was at least 5-fold larger than that needed to power for PFS.Table:

267P Summary of results

StudyTotal No. of patients in trial (randomisation if not 1:1)Observed median, months (arm A v B)Retrospectively calculated sample sizeFactor (x)
PFSTTPOSPFS/TTPOSOS sample size/NOS/PFS sample size
Ackland 2001460a6.3 v 8.7b18.2 v 20.1360590612.816.4
Jassem 2001267a6.2 v 8.3b18.3 v 23.3b59217926.73.0
Ejlertsen 2004387a8.2 v 10.1b18.0 v 19.178811 98831.015.2
Bontenbal 20052166.6 v 8.0b16.2 v 22.6b10224762.20.5
Feher 2005397a3.4 v 6.1b11.8 v 19.1b982120.52.2
von Minckwitz 2005364a6.7 v 8.2b820
Paridaens 2005331a3.9 v 7.5b15.6 v 18.38018825.723.5
Albain 20085294.0 v 6.1b15.8 v 18.6b16814042.78.4
Gray 20097225.8 v 11.3b24.8 v 26.572826211.4114.8
Sparano 20097517 v 9.8b20.6 v 20.52941 862 0102479.46333.4
Miles 2010488 (1:1:1)8.2 v 10.1b31.9 v 30.280220 80242.625.9
Robert 2011615 (1:2)5.7 v 8.6b22.8 v 25.723438406.216.4
Gligorov 20141854.3 v 11.9b23.7 v 39.0b342421.37.1
Lorusso 20142337.8 v 9.4b28.0 v 30.1972965441.49.9

Duration of accrual and/or follow-up not reported; accrual period assumed to be 1/3 of study duration.


Statistically significant.


Designing trials to test potential new treatments for HER2-negative mBC is challenging and requires a balance of regulatory acceptability, feasibility and realistic medical assumptions to calculate sample sizes, which can be particularly difficult in heterogeneous study populations with long post-progression survival and heterogeneous subsequent therapies. However, ongoing and future trials of cancer immunotherapy (new mode of action) focusing on triple-negative mBC (a more homogeneous population with shorter OS and post-progression survival, and fewer treatment options) may show a new pattern.

Clinical trial identification

Not applicable

Legal entity responsible for the study

Roche Pharma AG


Roche Pharma AG


S. Kümmel, C. Jackisch: Membership on advisory board: Roche Pharma AG. V. Müller: Membership on advisory board or board of directors: Amgen, AstraZeneca, Celgene, DaiichiSankyo, Eisai, Pfizer, Pierre-Fabre, Novartis, Roche, Teva, Janssen-Cilag, Genomic Health, Roche, Pierre Fabre, Amgen, Daiichi-Sankyo and Eisai. S. Klawitter: Roche Pharma AG (Employment). M.P. Lux: Membership on advisory board: Roche, Novartis, Pfizer, MSD, AstraZeneca; Corporate-sponsored research: Roche, Novartis, MSD, Celgene, Amgen. All other authors have declared no conflicts of interest.