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A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant
Siraj M Ali1, Jessica Watson2, Kai Wang1
1Foundation Medicine Inc., Cambridge, Mass., USA.
Abstract:
After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.
Insights
For metastatic triple-negative breast cancer (TNBC) resistant to standard therapies, a personalized treatment combining sorafenib and vorinostat showed promise in a patient with MCL1 amplification. This targeted approach extended the patient's life by six months.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Metastatic triple-negative breast cancer (TNBC) lacks effective therapies post-anthracycline and platinum treatment.
- MCL1 amplification, a common event in TNBC (≥20%), confers resistance to apoptosis.
- Comprehensive genomic profiling is crucial for identifying actionable targets in TNBC.
Observation:
- A patient with metastatic TNBC was found to have MCL1 amplification via comprehensive genomic profiling.
- The patient had failed standard anthracycline- and platinum-based chemotherapy.
- Hospice care was being considered due to disease progression.
Findings:
- A personalized, dose-reduced regimen of sorafenib and vorinostat was administered, based on preclinical data showing synergy in MCL1-amplified cancers.
- This targeted therapy resulted in a 6-month survival benefit for the patient.
- The regimen was well-tolerated, allowing for continued treatment.
Implications:
- MCL1 amplification represents a potential therapeutic vulnerability in a subset of TNBC patients.
- Targeted inhibition of MCL1, potentially with sorafenib and vorinostat, may offer a new treatment strategy for advanced TNBC.
- Further clinical trials are warranted to validate these findings and explore similar regimens in the MCL1-amplified TNBC population.
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