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Can contemporary trials of chemotherapy for HER2-negative metastatic breast cancer detect overall survival benefit?

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Can contemporary trials of chemotherapy for HER2-negative metastatic breast cancer detect overall survival benefit? / Kümmel, Sherko; Jackisch, Christian; Müller, Volkmar; Schneeweiss, Andreas; Klawitter, Sandra; Lux, Michael P.

In: CANCER MANAG RES, Vol. 10, 2018, p. 5423-5431.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kümmel, S, Jackisch, C, Müller, V, Schneeweiss, A, Klawitter, S & Lux, MP 2018, 'Can contemporary trials of chemotherapy for HER2-negative metastatic breast cancer detect overall survival benefit?', CANCER MANAG RES, vol. 10, pp. 5423-5431. https://doi.org/10.2147/CMAR.S177240

APA

Kümmel, S., Jackisch, C., Müller, V., Schneeweiss, A., Klawitter, S., & Lux, M. P. (2018). Can contemporary trials of chemotherapy for HER2-negative metastatic breast cancer detect overall survival benefit? CANCER MANAG RES, 10, 5423-5431. https://doi.org/10.2147/CMAR.S177240

Vancouver

Kümmel S, Jackisch C, Müller V, Schneeweiss A, Klawitter S, Lux MP. Can contemporary trials of chemotherapy for HER2-negative metastatic breast cancer detect overall survival benefit? CANCER MANAG RES. 2018;10:5423-5431. https://doi.org/10.2147/CMAR.S177240

Bibtex

@article{a49330c360784d678db23abadcd0231d,
title = "Can contemporary trials of chemotherapy for HER2-negative metastatic breast cancer detect overall survival benefit?",
abstract = "Purpose: Although several trials have demonstrated improved progression-free survival (PFS) with first-line regimens for HER2-negative metastatic breast cancer (mBC), overall survival (OS) benefit is elusive. We calculated required sample sizes to power for OS using published data from recent mBC trials.Patients and methods: Randomized superiority trials of first-line chemotherapy/targeted therapy for HER2-negative mBC including >150 patients, meeting the primary efficacy objective, and published in 2000-2018 were identified. The sample sizes required to power for PFS and OS were calculated retrospectively for each trial using observed results and study/recruitment follow-up durations (α=0.05, two-sided log-rank test, 80% power), and summarized as a factor (x) relative to actual sample size.Results: Nine of 13 identified trials reported all information required for retrospective sample size calculation. Six had sample sizes larger than required to demonstrate a significant PFS benefit but all would have required larger sample sizes to demonstrate significant OS benefit with the observed results. In ten trials, the required sample size was ≥5-fold larger to power for OS than PFS.Conclusion: Designing trials to test potential new treatments for HER2-negative mBC is challenging, requiring a balance of regulatory acceptability, feasibility, and realistic medical assumptions to calculate sample sizes. Powering for OS is particularly difficult in heterogeneous populations with long postprogression survival, potential crossover, heterogeneous poststudy therapy, and evolving treatment standards. Validated surrogate endpoints are critical. Ongoing trials of cancer immunotherapy (new mode of action) in triple-negative mBC (more homogeneous, shorter OS and postprogression survival, fewer treatment options) may show a new pattern.",
keywords = "Journal Article",
author = "Sherko K{\"u}mmel and Christian Jackisch and Volkmar M{\"u}ller and Andreas Schneeweiss and Sandra Klawitter and Lux, {Michael P}",
year = "2018",
doi = "10.2147/CMAR.S177240",
language = "English",
volume = "10",
pages = "5423--5431",
journal = "CANCER MANAG RES",
issn = "1179-1322",
publisher = "DOVE MEDICAL PRESS LTD",

}

RIS

TY - JOUR

T1 - Can contemporary trials of chemotherapy for HER2-negative metastatic breast cancer detect overall survival benefit?

AU - Kümmel, Sherko

AU - Jackisch, Christian

AU - Müller, Volkmar

AU - Schneeweiss, Andreas

AU - Klawitter, Sandra

AU - Lux, Michael P

PY - 2018

Y1 - 2018

N2 - Purpose: Although several trials have demonstrated improved progression-free survival (PFS) with first-line regimens for HER2-negative metastatic breast cancer (mBC), overall survival (OS) benefit is elusive. We calculated required sample sizes to power for OS using published data from recent mBC trials.Patients and methods: Randomized superiority trials of first-line chemotherapy/targeted therapy for HER2-negative mBC including >150 patients, meeting the primary efficacy objective, and published in 2000-2018 were identified. The sample sizes required to power for PFS and OS were calculated retrospectively for each trial using observed results and study/recruitment follow-up durations (α=0.05, two-sided log-rank test, 80% power), and summarized as a factor (x) relative to actual sample size.Results: Nine of 13 identified trials reported all information required for retrospective sample size calculation. Six had sample sizes larger than required to demonstrate a significant PFS benefit but all would have required larger sample sizes to demonstrate significant OS benefit with the observed results. In ten trials, the required sample size was ≥5-fold larger to power for OS than PFS.Conclusion: Designing trials to test potential new treatments for HER2-negative mBC is challenging, requiring a balance of regulatory acceptability, feasibility, and realistic medical assumptions to calculate sample sizes. Powering for OS is particularly difficult in heterogeneous populations with long postprogression survival, potential crossover, heterogeneous poststudy therapy, and evolving treatment standards. Validated surrogate endpoints are critical. Ongoing trials of cancer immunotherapy (new mode of action) in triple-negative mBC (more homogeneous, shorter OS and postprogression survival, fewer treatment options) may show a new pattern.

AB - Purpose: Although several trials have demonstrated improved progression-free survival (PFS) with first-line regimens for HER2-negative metastatic breast cancer (mBC), overall survival (OS) benefit is elusive. We calculated required sample sizes to power for OS using published data from recent mBC trials.Patients and methods: Randomized superiority trials of first-line chemotherapy/targeted therapy for HER2-negative mBC including >150 patients, meeting the primary efficacy objective, and published in 2000-2018 were identified. The sample sizes required to power for PFS and OS were calculated retrospectively for each trial using observed results and study/recruitment follow-up durations (α=0.05, two-sided log-rank test, 80% power), and summarized as a factor (x) relative to actual sample size.Results: Nine of 13 identified trials reported all information required for retrospective sample size calculation. Six had sample sizes larger than required to demonstrate a significant PFS benefit but all would have required larger sample sizes to demonstrate significant OS benefit with the observed results. In ten trials, the required sample size was ≥5-fold larger to power for OS than PFS.Conclusion: Designing trials to test potential new treatments for HER2-negative mBC is challenging, requiring a balance of regulatory acceptability, feasibility, and realistic medical assumptions to calculate sample sizes. Powering for OS is particularly difficult in heterogeneous populations with long postprogression survival, potential crossover, heterogeneous poststudy therapy, and evolving treatment standards. Validated surrogate endpoints are critical. Ongoing trials of cancer immunotherapy (new mode of action) in triple-negative mBC (more homogeneous, shorter OS and postprogression survival, fewer treatment options) may show a new pattern.

KW - Journal Article

U2 - 10.2147/CMAR.S177240

DO - 10.2147/CMAR.S177240

M3 - SCORING: Journal article

C2 - 30519090

VL - 10

SP - 5423

EP - 5431

JO - CANCER MANAG RES

JF - CANCER MANAG RES

SN - 1179-1322

ER -