Impact of trastuzumab treatment beyond disease progression for advanced/metastatic breast cancer on survival – Results from a prospective, observational study in Germany

Jackisch, Christian; Welslau, Manfred; Schoenegg, Winfried; Selbach, Johannes; Harich, Hanns-Detlev; Schröder, J; Schmidt, Marcus; Göhler, Thomas; Eustermann, Heidi; Ringel, Ralf; Hinke, Axel

doi:10.1016/j.breast.2014.06.003

Cited by 14 publications

(8 citation statements)

References 17 publications

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“…Compared with the results from a prospective large observational study and a randomized phase III study involving metastatic breast cancer, which showed that the continued therapy with TBP improves the survival outcome of patients with metastatic HER2-positive breast cancer (19,20), the results of the present study did not demonstrate a clear survival time benefit associated with trastuzumab therapy following first disease progression. However, the magnitude of unadjusted HR (0.63) for PFS in the present study was of the same order as that (0.69) in a German phase III trial comparing trastuzumab plus capecitabine vs. capecitabine alone in HER2-positive breast cancer patients whose disease had progressed during trastuzumab therapy (20), a finding which justified further investigation of HER2-positive AGC.…”

Section: Discussioncontrasting

confidence: 98%

“…Preliminary evidence from a small phase II study demonstrated that a trastuzumab plus docetaxel-containing regimen was well tolerated and effective for HER2-positive AGC previously treated with fluorouracil-based chemotherapy; however, in this study, the patients had received no previous therapy with trastuzumab (18). On the other hand, several studies have reported that continued therapy with trastuzumab beyond progression (TBP) improves the survival outcome of patients with metastatic HER2-positive breast cancer (19,20), and represents a practical therapeutic option. However, there is currently no clinical data regarding the efficacy of trastuzumab for HER2-positive AGC progressing during trastuzumab-based chemotherapy.…”

Section: Correlation Between Human Epidermal Growth Factor Receptor 2mentioning

confidence: 81%

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Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Kadowaki¹,

Masuishi²,

Taniguchi³

et al. 2017

Oncology Letters

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Abstract. There is currently no clinical data regarding the efficacy of trastuzumab treatment for the progression of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) occurring during trastuzumab-based chemotherapy. The aim of this study was to retrospectively examine the clinical benefits of trastuzumab for HER2-positive AGC patients who progressed during first-line trastuzumab-based chemotherapy. Among the 108 patients treated with trastuzumab combined with fluoropyrimidine and cisplatin as first-line therapy, 46 HER2-positive AGC patients who received cytotoxic agents with or without trastuzumab subsequent to disease progression were included. Of these, the efficacy and safety outcomes of 26 patients who continued trastuzumab were compared with those of the 20 patients who discontinued trastuzumab. No difference in response rate (18.2 vs. 15.8%, P=1.00) was observed between the two groups. Progression-free survival (PFS) time was numerically longer in the chemotherapy combination with trastuzumab group than in the chemotherapy combination without trastuzumab group (median, 4.0 vs. 2.3 months), with no significance [hazard ratio (HR), 0.63; P=0.14]. In the subset analysis, continuation of trastuzumab significantly improved PFS time in selected subgroups of patients with tumors exhibiting HER2 expression scores of 3+ (HR, 0.41; P=0.04), intestinal-type histology (HR, 0.32; P<0.01), and a first PFS time of >6 months (HR, 0.44; P=0.04). The survival times for the trastuzumab beyond progression (TBP) and non-TBP groups were similar (HR, 1.06; P=0.88), with equivalent overall survival times in the subgroups with immunohistochemistry scores of 3+ (HR, 0.97; P=0.94), 0.53; P= 0.19), and a first PFS time of >6 months (HR, 0.62; P=0.31). There were no differences in the incidence rates of toxicity, including cardiac dysfunction, between the two groups. The study results suggest that selected HER2-positive AGC patients may benefit from trastuzumab continuation during first progression, and further prospective studies are warranted.

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Section: Discussioncontrasting

confidence: 98%

Section: Correlation Between Human Epidermal Growth Factor Receptor 2mentioning

confidence: 81%

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Kadowaki¹,

Masuishi²,

Taniguchi³

et al. 2017

Oncology Letters

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“…Both univariate and multivariate analyses suggested distinctly longer survival in the 261 patients with continued trastuzumab treatment. These results are presented in a separate publication [ 9 ].…”

Section: Resultsmentioning

confidence: 99%

Trastuzumab in advanced breast cancer – a decade of experience in Germany

Jackisch

Schoenegg²,

Reichert³

et al. 2014

BMC Cancer

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BackgroundTrastuzumab was registered in 2000 for the treatment of metastatic breast cancer, both as monotherapy and combination therapy with paclitaxel. In this prospective, non-interventional observation study, the 10-year experience with trastuzumab in the routine management of HER2-positive breast cancer was reviewed.MethodsBetween 2000 and 2010, 1843 evaluable patients with advanced HER2-positive breast cancer were recruited in 223 institutions across Germany. Patients were prospectively monitored for about one year. Additional information on long-term outcomes, progression-free survival (PFS), and overall survival (OS) were retrieved at several follow-up points. There were no restrictions with respect to diagnostic or therapeutic procedures. Patients were stratified into three cohorts depending on the treatment regimen, i.e. trastuzumab monotherapy (n =228, 12%), trastuzumab combined with chemotherapy (n =1346, 73%), or trastuzumab combined with endocrine therapy (n =269, 15%).ResultsMedian age was 59.5 years with a proportion of 28% being older than 65 years. Over a maximum follow-up period of more than 10 years, 1538 PFS events were documented in 83% of patients, resulting in an estimated median PFS of 11.8 months. Median OS, based on recorded death in 64% of patients, amounted to 34.4 months, with 48% (95% confidence intervals 45 – 50%) still alive after three years. The subgroup selected for a treatment combination with endocrine drugs only had distinctly longer PFS and OS than the other two groups, achieving medians of 23.3 months and 56.3 months, respectively. Median PFS and OS in elderly patients over 65 years of age was 11.4 months and 28.3 months, respectively. Adverse reactions, including cardiac toxicity, of severity grade 3 or 4 were rare.ConclusionsThe superior outcome of treatment strategies including trastuzumab in HER2 overexpressing breast cancer, proven in pivotal studies, was confirmed in the management of advanced breast cancer in Germany in the routine setting. Our data suggest a comparable clinical benefit of treatment with trastuzumab in elderly patients (>65 years), who are typically under-represented in randomized clinical studies.

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“…Accumulating evidence supports the benefits of continuing trastuzumab beyond disease progression in patients with HER2-positive breast cancer 93,94 . The results of these studies suggest that continuing trastuzumab after progressive disease in gastroesophageal cancer is a viable option; however, large prospective studies in patients with gastroesophageal cancer are needed to confirm this approach.…”

Section: Her2-positive Diseasementioning

confidence: 99%

Clinical impact of tumour biology in the management of gastroesophageal cancer

2016

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The characterization of oesophageal and gastric cancer into subtypes based on genotype has evolved in the past decade. Insights into the molecular landscapes of gastroesophageal cancer provide a roadmap to assist the development of new drugs and their use in combinations, for patient stratification, and for trials of targeted therapies. Trastuzumab is the only approved treatment for gastroesophageal cancers that overexpress HER2. Acquired resistance usually limits the duration of response to this treatment, although a number of new agents directed against HER2 have the potential to overcome or prolong the time until resistance occurs. Beyond that, anti-VEGFR2 therapy with ramucirumab was the first biological treatment strategy to produce a survival benefit in an unselected population of patients with chemotherapy-refractory gastroesophageal cancer. Large initiatives are starting to address the role of biomarker-driven targeted therapy in the metastatic and in the perioperative setting for patients with this disease. Immunotherapy also holds promise, and our understanding of subsets of gastroesophageal cancer based on patterns of immune response continues to evolve. Efforts are underway to identify more relevant genomic subsets through genomic screening, functional studies, and molecular characterization. Herein, we provide an overview of the key developments in the treatment of gastroesophageal cancer, and discuss potential strategies to further optimize therapy by targeting disease subtypes.

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Impact of trastuzumab treatment beyond disease progression for advanced/metastatic breast cancer on survival – Results from a prospective, observational study in Germany

Cited by 14 publications

References 17 publications

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Trastuzumab in advanced breast cancer – a decade of experience in Germany

Clinical impact of tumour biology in the management of gastroesophageal cancer

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