Targeted Treatment of Metastatic Breast Cancer in the 2nd Line – Experiences from Practice
The recommended treatment for metastatic HER2-positive breast cancer in the 1st line involves dual blockade of the HER2 signaling pathway using trastuzumab and pertuzumab in combination with a taxane cytostatic. After the failure of this therapy, treatment with trastuzumab emtansine (T-DM1) is recommended. However, this recommendation is not supported by a prospectively designed controlled study examining the outcomes of this therapeutic sequence. Therefore, a group of Italian authors decided to publish the results of a patient cohort treated with this sequence in real clinical practice conditions.
T-DM1 in the Treatment of HER2-Positive Breast Tumors
T-DM1 is a conjugate of a microtubule inhibitor (emtansine complex) with trastuzumab, a monoclonal antibody targeting the HER2 receptor. After binding of T-DM1 to the surface of a cell expressing HER2, the entire complex is internalized and the cytostatic is delivered directly to the tumor cell. The advantage of this treatment is especially its lower toxicity.
T-DM1 is recommended in several guidelines as the preferred 2nd line treatment after therapy with trastuzumab, pertuzumab, and a taxane. However, there are conflicting data regarding its reduced efficacy after the combination of pertuzumab with trastuzumab, or its reduced efficacy in advanced lines of treatment. The presented study describes the results of a cohort of patients from 7 Italian oncology centers.
Analyzed Patient Cohort
The retrospective analysis included 135 patients (aged 34–87 years) with metastatic HER2-positive breast cancer, who were treated in the 1st line with trastuzumab, pertuzumab, and docetaxel. The median duration on 1st line therapy was 15.6 months, the treatment was clinically beneficial for 50% of the patients in the cohort, and the overall response rate (ORR) to the therapy was 42%.
All patients were subsequently treated with T-DM1 at the standard dosage of 3.6 mg/kg i.v. every 21 days. The primary goal of the analysis was to evaluate the efficacy of the treatment in the 2nd line.
Results
Efficacy
The ORR in the 2nd line treatment was 20.7%, 44% of patients remained on treatment for more than 1 year, and clinical benefit (complete/partial response to treatment or stable disease for at least 6 months) was observed in 57.7% of the patients. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI] 8.6–12.7 months).
Safety
Adverse events during the treatment were generally of grade 1–2; the most common included elevation of liver enzymes (25%) and asthenia (21%). Grade 2 hematological toxicities occurred in about 3% of patients, and there was 1 case of grade 3 neutropenia. Adverse events did not require dose adjustment and were manageable according to the procedures outlined in the SPC.
Conclusion
Treatment with T-DM1 maintains efficacy and safety even after the progression of metastatic HER2-positive breast cancer on dual blockade with a combination of pertuzumab/trastuzumab. For approximately half of the patients, the initiation of T-DM1 in the 2nd line was clinically beneficial, and the treatment exhibited low toxicity. T-DM1 appears to be a suitable therapy for the 2nd and subsequent lines of treatment for this metastatic disease.
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References:
1. Prete S. D., Montella L., Arpino G. et al. Second line trastuzumab emtansine following horizontal dual blockade in a real-life setting. Oncotarget 2020; 11 (22): 2083–2091, doi: 10.18632/oncotarget.27603.
2. SPC Kadcyla. Available at: www.ema.europa.eu/documents/product-information/kadcyla-epar-product-information_cs.pdf
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