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Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

ABSTRACT: BACKGROUND:The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response. METHODS:This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed. RESULTS:Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31-72) and of 18% (95%CI 10-30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit. CONCLUSION:Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies. TRIAL REGISTRATION:NCT00004935 ; first posted 27.01.2003, retrospectively registered.

SUBMITTER: Schmid S

PROVIDER: S-EPMC6734335 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

Schmid Sabine S Klingbiel Dirk D Aebi Stefan S Goldhirsch Aron A Mamot Christoph C Munzone Elisabetta E Nolè Franco F Oehlschlegel Christian C Pagani Olivia O Pestalozzi Bernhard B Rochlitz Christoph C Thürlimann Beat B von Moos Roger R Weder Patrik P Zaman Khalil K Ruhstaller Thomas T

BMC cancer 20190910 1

<h4>Background</h4>The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response.<h4>Methods</h4>This is an unplanned post-hoc analysis of p ...[more]

PMID: 31500588

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) have significantly improved survival for advanced wild-type non-small cell lung cancer, but there is no direct comparison to confirm which first-line treatment may lead to the longest overall survival. What qualifies as long-term survival (LS) is even unclear.MethodsBy searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2005 to December 2020, we included randomized controlled trials (RCTs) of first-line ICI-containing treatments to perform an integrated analysis (IA) to determine the criterion of LS and then screened regimens with LS for network meta-analysis (NMA). The main outcomes for NMA were median overall survival (mOS), 1-year survival rate (1ySR), and 2-year survival rate (2ySR); those for IA were the pooled mOS (POS), 1ySR (P1SR), and 2ySR (P2SR).ResultsBy IA of 16 first-line ICIs from 20 RCTs, the POS was 16.20 (95% CI 14.79-17.60) months, with P1SR of 63% (95% CI 59-66%) and P2SR of 37% (33-41%). Thus, we defined LS as mOS ≥ POS (16.20 m) for regimens and screened for RCTs with outcomes meeting this criterion. Eleven ICI-based regimens can bring LS for the overall population, among which ICI with bevacizumab and chemotherapy achieved the longest POS of 19.50 m (16.90-22.10 m) and the highest P1SR (74%, 61%-87%) and P2SR (49%, 38%-61%). Pembrolizumab with chemotherapy ranked first in mOS and 1ySR, while atezolizumab plus bevacizumab and chemotherapy ranked first in 2ySR.ConclusionsThrough the IA of first-line treatment regimens, a POS of 16.20 m can be determined as the LS standard. Further considering 1ySR and 2ySR, atezolizumab combined with bevacizumab and chemotherapy or pembrolizumab plus chemotherapy are likely to bring the longest LS in the overall population, while single ICI may be adequate for patients with a high PD-L1 expression. ICIs with bevacizumab and chemotherapy may be the best combination for LS for its further advantage over time.

Project description:BackgroundResults from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources.ObjectiveTo assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting.Design, setting, and participantsWe modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy.InterventionSOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles.Outcome measurements and statistical analysisThe model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs).Results and limitationsThe model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled.ConclusionsDocetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available.Patient summaryStarting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

Dataset Information

Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

Publications

Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

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