Trastuzumab Treatment beyond Progression in Advanced Breast Cancer: Patterns of Care in Six Swiss Breast Cancer Centers

Huober, Jens; Baumann, Michaël; Rochlitz, Christoph; Aebi, Stefan; Güth, Uwe; Moos, Roger von; Müller, Andreas; Rohr, Lukas von; Widmer, Isabelle; Thürlimann, Beat

doi:10.1159/000333396

Cited by 8 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Overall survival (OS) at 24 months was chosen as the primary end point, and the sample size relied on an assumed median OS of 32 months in both arms based on data from the most recent trials at the time the trial was planned. 2,3 Our results show that the proportion of patients known to be alive at 2 years was 79.0% (90% CI, 71.4%-85.4%) and 78.1% (90% CI, 70.4%-84.5%) for arm A without and arm B with additional chemotherapy, respectively, with overlapping CIs. 1 The conclusions in our trial 1 were based on purely descriptive outcomes including efficacy, safety, and quality of life and without formal comparisons of efficacy differences between treatment arms, since we chose a randomized phase 2 design to address the question of a chemotherapy-free first-line treatment in patients with ERBB2-positive advanced breast cancer.…”

mentioning

confidence: 71%

“…The PERNETTA trial was an open-label, phase 2, noncomparative parallel-design with confidence interval approach in patients with centrally confirmed newly diagnosed ERBB2-positive metastatic breast cancer . Overall survival (OS) at 24 months was chosen as the primary end point, and the sample size relied on an assumed median OS of 32 months in both arms based on data from the most recent trials at the time the trial was planned . Our results show that the proportion of patients known to be alive at 2 years was 79.0% (90% CI, 71.4%-85.4%) and 78.1% (90% CI, 70.4%-84.5%) for arm A without and arm B with additional chemotherapy, respectively, with overlapping CIs …”

mentioning

confidence: 97%

See 1 more Smart Citation

Is Pertuzumab Plus Trastuzumab Without Chemotherapy a Reasonable Treatment for ERBB2-Positive Metastatic Breast Cancer?—Reply

Huober,

Thürlimann,

Dietrich

2024

JAMA Oncol

Self Cite

View full text Add to dashboard Cite

To the Editor Huober and colleagues 1 conducted an important analysis of a randomized clinical trial to assess if it is reasonable for patients to receive first-line pertuzumab plus trastuzumab alone (group A) vs with chemotherapy (group B) followed by trastuzumab and emtansine after progression. The median progression-free survival was 8.4 and 23.3 months for group A and group B, respectively, suggesting that patients would have impressive statistically and clinically significant treatment benefit with chemotherapy. The authors then evaluated overall survival (OS) between 2 treatment strategies based on the 2-year survival rates, which were 79.0% (90% CI, 71.4%-85.4%) for group A and 78.1% (90% CI, 70.4%-84.5%) for group B. Note that both confidence intervals were rather large, indicating that there was not enough information to assess the relative merit between the 2 arms using this summary measure for OS.From Figure 2B, 1 the Kaplan-Meier curves for the OS are stretching out to 72 months and provide much more information about the survival profile beyond 2-year rates. In fact, the survival curve for group B is uniformly better than its counterpart for group A, especially between 24 and 72 months. With reconstructed survival data 2 from Figure 2B, the areas under the Kaplan-Meier curves up to 72 months are 50.2 and 54.2 months for group A and group B, respectively. 3,4 That is, patients in group A on average would survive 50.2 months with 72 months of follow-up. The difference (B minus A) is 4.00 months (95% CI, −2.4 to 10.3 months), which is rather asymmetric, favoring the treatment with chemotherapy. That is, the patients in the chemotherapy group might have 10.3 extra months of survival benefit but only have 2.4 months shorter survival compared with patients not receiving chemotherapy. Due to the small trial size, this treatment difference estimate for OS being not statistically significant would be expected. Based on the above totality of the progression-free survival and OS analysis results, it is not clear if we can conclude that the treatment without chemotherapy is feasible, as the authors claimed in the article. 1

show abstract

mentioning

confidence: 71%

mentioning

confidence: 97%

Is Pertuzumab Plus Trastuzumab Without Chemotherapy a Reasonable Treatment for ERBB2-Positive Metastatic Breast Cancer?—Reply

Huober,

Thürlimann,

Dietrich

2024

JAMA Oncol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, the tumor did not progress any further with extended crizotinib treatment but has remained stable to date. Evidence for ‘treatment beyond progression' was demonstrated for trastuzumab in breast cancer, and warrants further study in NSCLC molecular subtypes as well [20]. …”

Section: Resultsmentioning

confidence: 99%

Experience in Integrating <i>ALK</i> Testing and Crizotinib into the Routine Treatment of Patients with Non-Small Cell Lung Cancer

Gautschi¹,

Schefer

Riklin³

et al. 2013

Oncol Res Treat

View full text Add to dashboard Cite

Background: Crizotinib, an inhibitor of the anaplastic lymphoma kinase (ALK), is approved since 2012 in Switzerland for use in ALK-rearranged advanced pretreated non-small cell lung cancer (NSCLC). Patients and Methods: Here we describe our own experience with crizotinib and ALK testing via fluorescence in-situ hybridization (FISH) in the first 10 ALK-positive patients who were treated in central Switzerland in 2011 on a compassionate use basis. Results: We have demonstrated that FISH testing for ALK can be performed simultaneously with other diagnostic procedures, providing oncologists with results in a timely manner to make informed decisions about patient treatment. The majority of our patients treated with crizotinib had a clinical benefit, and the drug was tolerated well. Conclusion: The clinical development of crizotinib has been extremely rapid. Nonetheless, by the time crizotinib was approved, many centers including our own had local testing in place and clinical experience with the drug. This emphasizes the importance of broad clinical studies and compassionate use programs in oncology.

show abstract

“…However, the vast majority of patients received chemotherapy as well as endocrine treatments patients at some point in their disease course and therefore de-escalation of treatment in most cases has to be understood as a deferring approach . This approach has been already adopted in clinical practice mainly based on general principles usually used in the management of metastatic breast cancer and on clinical experience treating physicians [15].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Trastuzumab Treatment beyond Progression in Advanced Breast Cancer: Patterns of Care in Six Swiss Breast Cancer Centers

Cited by 8 publications

References 44 publications

Is Pertuzumab Plus Trastuzumab Without Chemotherapy a Reasonable Treatment for ERBB2-Positive Metastatic Breast Cancer?—Reply

Is Pertuzumab Plus Trastuzumab Without Chemotherapy a Reasonable Treatment for ERBB2-Positive Metastatic Breast Cancer?—Reply

Experience in Integrating <i>ALK</i> Testing and Crizotinib into the Routine Treatment of Patients with Non-Small Cell Lung Cancer

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

Contact Info

Product

Resources

About