Lapatinib and capecitabine as third-line therapy in young woman with advanced breast cancer

We report the case of a young woman with HER2-positive advanced breast cancer, arising during pregnancy, with visceral involvement at onset, treated with third line therapy with the combination lapatinib and capecitabine resulting in a nearly complete long-term tumor response . The patient had previously been treated with first line therapy with double block, pertuzumab and trastuzumab and, after disease progression, with T-DM1 resulting in a short-term stability of clinical status (Oncology).

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Abstract OT1-1-02: A single-arm phase IIIb study of pertuzumab and trastuzumab with a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (PERUSE)

10.1158/0008-5472.sabcs12-ot1-1-02 ◽

2012 ◽

Cited By ~ 4

Author(s):

T Bachelot ◽

E Ciruelos ◽

T Peretz-Yablonski ◽

A Schneeweiss ◽

F Puglisi ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Advanced Breast ◽

First Line ◽

Her2 Positive ◽

First Line Therapy ◽

Line Therapy ◽

Phase Iiib

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A randomized and open-label trial evaluating the addition of pazopanib to lapatinib as first-line therapy in patients with HER2-positive advanced breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-012-2399-4 ◽

2013 ◽

Vol 137 (3) ◽

pp. 755-766 ◽

Cited By ~ 33

Author(s):

Stephen R. D. Johnston ◽

Henry Gómez ◽

Salomon M. Stemmer ◽

Maria Richie ◽

Michael Durante ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Advanced Breast ◽

First Line ◽

Her2 Positive ◽

Open Label ◽

First Line Therapy ◽

Line Therapy ◽

Open Label Trial

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Clinical Activity of Trastuzumab and Vinorelbine in Women With HER2-Overexpressing Metastatic Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.10.2722 ◽

2001 ◽

Vol 19 (10) ◽

pp. 2722-2730 ◽

Cited By ~ 273

Author(s):

Harold J. Burstein ◽

Irene Kuter ◽

Susana M. Campos ◽

Rebecca S. Gelman ◽

Laura Tribou ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Cardiac Toxicity ◽

Response Rate ◽

Metastatic Breast ◽

Advanced Breast ◽

Clinical Activity ◽

Her2 Positive ◽

First Line Therapy ◽

Line Therapy

PURPOSE: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg × 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m2 weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), or both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20%), taxanes (15%), or both types (38%) of chemotherapy. RESULTS: Responses were observed in 30 of 40 patients (overall response rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients had symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity. CONCLUSION: Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerated.

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Current and future landscape of targeted therapy in HER2-positive advanced breast cancer: redrawing the lines

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211066677 ◽

2022 ◽

Vol 14 ◽

pp. 175883592110666

Author(s):

Christine Simmons ◽

Daniel Rayson ◽

Anil Abraham Joy ◽

Jan-Willem Henning ◽

Julie Lemieux ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Phase Ii ◽

Advanced Breast ◽

Phase Iii ◽

Second Line ◽

Her2 Positive ◽

Line Therapy ◽

Phase Iii Trials ◽

Third Line

Background: Evidence to date supports continued human epidermal growth factor receptor 2 (HER2) suppression beyond progression on HER2-directed therapy for advanced HER2-positive breast cancer. Data from several phase II and III trials evaluating HER2-directed therapy following second-line T-DM1 have recently become available. Methods: We performed a systematic search of the published and presented literature to identify phase II and phase III trials assessing novel HER2-targeted agents as third-line therapy or beyond for HER2-positive advanced breast cancer using search terms ‘breast cancer’ AND ‘HER2’ AND ‘advanced’ AND (‘phase II’ OR ‘phase III’). Results: Eight clinical trials reporting efficacy outcomes on third-line or greater HER2-directed therapy for HER2-positive advanced breast cancer were identified. In phase III trials, margetuximab and neratinib combinations demonstrated significant 1.3-month (hazard ratio, HR = 0.71, p < 0.001) and 0.1-month (HR = 0.76, p = 0.006) net improvements in median progression-free survival (PFS), respectively, with no significant improvements in overall survival (OS). Tucatinib added to trastuzumab and capecitabine demonstrated a significant 2.7-month improvement in median PFS (HR = 0.57, p < 0.00001) and a 5.5-month improvement in median OS (HR = 0.73, p = 0.004) in a randomized phase II trial, including significant clinical benefit for patients with brain metastases. Finally, trastuzumab-deruxtecan, zenocutuzumab, and poziotinib demonstrated benefit in phase II trials with the most robust overall response rate (62.0%) and median duration of response (18.2 months) observed for trastuzumab-deruxtecan among heavily pretreated patients. Conclusion: Tucatinib plus trastuzumab and capecitabine significantly prolongs OS, and promising preliminary response outcomes for trastuzumab-deruxtecan suggest that sequencing of these regimens following second-line therapy is reasonable.

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