Trastuzumab Beyond Progression in Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: A German Breast Group 26/Breast International Group 03-05 Study

Minckwitz, Gϋnter von; Bois, Andreas du; Schmidt, Marcus; Maass, Nicolaì; Čufer, Tanja; Jongh, Felix E. de; Maartense, E.; Zielinski, Christoph; Kaufmann, M.; Bauer, Wolfgang; Baumann, Klaus; Clemens, Michael; Duerr, Ralph; Uleer, Christoph; Andersson, Michael; Stein, Robert; Nekljudova, Valentina; Loibl, Sibylle

doi:10.1200/jco.2008.19.6618

Cited by 610 publications

(380 citation statements)

References 23 publications

(7 reference statements)

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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: Discussionmentioning

confidence: 45%

“…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. The phenomenon of clinically relevant improvement of PFS time in the subgroup of patients with HER2 IHC 3+ tumors is congruent with the exploratory findings from the ToGA and TyTAN trials (16,17).…”

Section: Discussionmentioning

confidence: 54%

“…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: 60%

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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: Discussionmentioning

confidence: 45%

Section: Discussionmentioning

confidence: 54%

Section: Correlation Between Human Epidermal Growth Factor Receptor 2mentioning

confidence: 60%

See 1 more Smart Citation

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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“…Two recent randomized clinical trials have documented the benefit on overall response of continued use of trastuzumab in women with HER2 positive breast cancer who experienced progression during trastuzumab treatment [7,8]. Here we show from a study of clinical practice in Italy that continued trastuzumab treatment after disease progression has clinically and statistically significant effects, remarkably in both RECIST responder and non-responder MBC patients upon first line trastuzumab treatment.…”

Section: Discussionmentioning

confidence: 55%

“…Several retrospective studies published thus far (reviewed in [3,4]) [5,6] have indicated a certain overall response rate, clinical benefit and extended time to progression from the use of a second trastuzumabcontaining regimen in HER2-positive MBC patients who progressed on first-line trastuzumab treatment. Moreover, two recent randomized trials designed to directly evaluate the efficacy of continuing trastuzumab after progression demonstrated the potential clinical utility of continuing trastuzumab even for patients with progressive disease [7,8]. To further evaluate the benefits of trastuzumab-continuation therapy we carried out a retrospective analysis of 272 HER2 positive MBC patients first line trastuzumab treated in the metastatic setting at different oncology centers in Italy, who continued or discontinued trastuzumab at progression.…”

Section: Introductionmentioning

confidence: 99%

Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study

Campiglio

Bufalino

Sandri

et al. 2011

Breast Cancer Res Treat

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ResultsOf the 272 HER2-positive MBC patients, 154 (56.6%) continued treatment. 79 (51.3%) of those 154 patients showed responses based on RECIST criteria during first-line trastuzumab-treatment.Of the 118 patients that suspended trastuzumab, RECIST responses had been observed in 44 (37.3%). Cox proportional hazards analysis of progressed patients, matched using propensity score, showed that discontinuation of trastuzumab at metastatic disease progression was a risk factor for significantly reduced overall survival in both responder (HR = 2.23; 95% CI = 1.03 to 4.82) and non-responder groups (HR = 3.53, 95% CI = 1.73 to 7.21), with no significant differences in the two estimated HRs (p-value of the likelihood-ratio test = 0.690). 4 ConclusionsContinued trastuzumab treatment after disease progression has clinically and statistically significant effects in both RECIST responder and non-responder MBC patients.

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Breast Cancer Treatment

Waks

Winer

2019

JAMA

2,924

2,138

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orldwide, breast cancer is the most common cancer in women, other than nonmelanoma skin cancer. 1 More than 250 000 new cases of breast cancer were diagnosed in the United States in 2017, and breast cancer will be diagnosed in 12% of all women in the United States over their lifetimes. 2 This review summarizes evidence-based approaches to the systemic and local treatment of the 3 major breast cancer subtypes: hormone receptor positive/ERBB2 negative (HR+/ERBB2−), ERBB2 positive (ERBB2+), and triple-negative. MethodsWe searched PubMed for English-language articles related to the treatment of breast cancer, with a focus on large randomized clini-cal trials or meta-analyses and guidelines of major professional societies. The indices of major medical and oncology journals were comprehensively reviewed for articles published from January 1, 2013, to November 11, 2018, on the topic of breast cancer treatment. Articles agreed on by both authors to define modern practice were included, with priority given to prospective randomized trials and large meta-analyses that represent the first and/or the most important evidence establishing current standard of care in breast cancer. Clinical PresentationIn the modern era of widespread screening mammography, more than half of breast cancers in the United States are diagnosed on screening mammogram, and approximately one-third IMPORTANCE Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer.OBSERVATIONS Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2): hormone receptor positive/ERBB2 negative (70% of patients), ERBB2 positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer-specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive and ERBB2 positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor-positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients with ERBB2-positive tumors receive ERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performe...

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Trastuzumab Beyond Progression in Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: A German Breast Group 26/Breast International Group 03-05 Study

Abstract: Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2-positive breast cancer who experienced progression during trastuzumab treatment.

Cited by 610 publications

References 23 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

Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study

Breast Cancer Treatment

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