Sorafenib for the treatment of breast cancer
Giuseppe Bronte1, Daniele Andreis2, Sara Bravaccini3
1a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
Introduction:
Breast cancer treatment includes many options depending on the tumor clinicopathological profile, which groups breast cancer into various subtypes. Bevacizumab is currently the only drug capable of targeting angiogenesis in breast cancer. Sorafenib has also been studied in combination with other agents. Areas covered: Pharmacological aspects of sorafenib, including results from preclinical studies on breast cancer cells; findings about clinical efficacy and safety in both single-arm and randomized clinical trials; ongoing trials. Expert opinion: Since sorafenib as a single agent has shown limited efficacy in breast cancer, its combination with other drugs is under investigation. Dose reduction is the main challenge when sorafenib is combined with chemotherapy or endocrine therapy. Although randomized phase-II trials on sorafenib plus chemotherapy versus chemotherapy alone have shown potential benefits in progression-free survival, preliminary results from a phase-III study in combination with capecitabine are negative. The definitive results of this trial and results from other ongoing phase-II trials will determine further developments of sorafenib in breast cancer. Although these additional data could help determine the most appropriate dose, drug combination and patient settings, a confirmation of the preliminary negative results reported in the phase-III trial are likely to discourage further use of sorafenib in breast cancer, given its non-negligible toxicity, lack of predicting markers, and the number of more promising drugs for breast cancer.
Insights
Sorafenib shows limited efficacy as a single breast cancer treatment. Combination therapies are under investigation, but dose adjustments and negative phase-III trial results may limit its future use.
Area of Science:
- Oncology
- Pharmacology
Background:
- Breast cancer treatment varies by subtype.
- Bevacizumab targets angiogenesis; sorafenib is studied in combination.
- Sorafenib's efficacy as a single agent is limited.
Purpose of the Study:
- To review sorafenib's pharmacological aspects in breast cancer.
- To analyze preclinical and clinical data on sorafenib's efficacy and safety.
- To discuss ongoing trials and future prospects of sorafenib in breast cancer treatment.
Main Methods:
- Review of preclinical studies on breast cancer cells.
- Analysis of single-arm and randomized clinical trials.
- Inclusion of data from ongoing clinical trials.
Main Results:
- Preclinical studies show sorafenib's effects on breast cancer cells.
- Phase-II trials suggest potential progression-free survival benefits with sorafenib plus chemotherapy.
- Preliminary phase-III results combining sorafenib with capecitabine are negative.
Conclusions:
- Sorafenib's combination with other drugs is being investigated.
- Dose reduction is a challenge when combining sorafenib with chemotherapy or endocrine therapy.
- Further trial results are needed to determine sorafenib's role, but negative phase-III findings may limit its use due to toxicity and lack of predictive markers.
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