Clinical Challenges > > ESMO: Metastatic Breast Cancer– It might just get more made complex as brand-new choices are authorized
by Leah Lawrence, Contributing Writer, MedPage Today November 26, 2023
As brand-new treatment alternatives continue to emerge for triple-negative breast cancer (TNBC), sequencing of treatment guarantees to get ever more complex.
TNBC had actually been approximated to represent approximately 15% of all breast cancer diagnoses but that percentage diminished with the new HER2-low classification, which represents around one-third of clients detected with TNBC. An essential more subset is those with BRCA-mutant illness.
“Only about 10% to 15% of clients detected with TNBC will also have a BRCA anomaly,” stated Yuan Yuan, MD, PhD, director of breast oncology at Cedars-Sinai Cancer in Los Angeles.
It is necessary to identify these patients with BRCA anomaly since they may be eligible for extra targeted treatments as part of the disease treatment regimen. For patients with chronic or stage IV disease, the National Comprehensive Cancer Network (NCCN) currently recommends comprehensive germline and somatic profiling to identify candidates for targeted agents.
“The NCCN just recently removed the age restriction on their guidelines for germline screening for women with TNBC to recommend that all be tested,” stated Kelly McCann, MD, PhD, of UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles. “You may only find a handful of people with BRCA anomalies, but for that handful it means they may live longer.”
In addition to genetic testing, Yuan said that PD-L1 testing is also a vital part of the work-up of patients with TNBC and may help narrow first-line treatment options. That is because patients with TNBC whose tumors show PD-L1 with a combined positive score (CPS) of 10 or more are eligible for treatment with pembrolizumab (Keytruda) plus chemotherapy.
The KEYNOTE-355 trial evaluated pembrolizumab 200 mg every 3 weeks plus the investigator’s choice of chemotherapy versus chemotherapy alone and revealed that the addition of pembrolizumab significantly improved overall survival (OS) in patients with a PD-L1 CPS score of 10 or more (HR 0.73, 95% CI 0.55-0.95, P=0.0185).
“Based on those results, patients with tumors that are PD-L1 positive can receive pembrolizumab with a backbone of nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin,” Yuan noted.
For those patients with TNBC and BRCA anomalies whose tumors do not show PD-L1, first-line treatment options include platinum-based chemotherapy or one of the two PARP inhibitors approved for this setting. “There are definitely some caveats here, and the best approach is up for debate,” Yuan said. “There is no right or wrong answer.”
The FDA approved olaparib (Lynparza) is based on results from the OlympiAD trial, which evaluated the PARP inhibitor versus physician’s choice of chemotherapy in patients with HER2-negative metastatic breast cancer. Olaparib significantly improved progression-free survival (PFS) compared to chemotherapy (HR 0.58,