Triple-negative breast cancer has been and remains challenging to treat and is high risk, but there has been progress made with new drug approvals and early-stage treatment. Dr. Steven J. Isakoff discusses these treatments further at the CURE® Educated Patient® Breast Cancer Summit.
“The good news is treatment options are expanding and outcomes are improving (for early-stage triple-negative breast cancer), but the challenge is it’s becoming increasingly important to balance the efficacy of these treatments with toxicity,” notes Isakoff.
Adjuvant Therapy
Adjuvant therapy has been standard therapy for early-stage triple-negative breast cancer, and there have been improvements in this area over the past few years. Previously, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) were superior treatment options, but more recently, Docefrez (docetaxel) and Cytoxan were considered superior to those prior treatment options. This led to the question of whether Adriamycin was still needed.
The ABC Trials assessed whether Adriamycin is still important in node-positive or high-risk node negative patients, and results demonstrated that it still added value specifically in patients with hormone receptor negative and lymph node positive disease.
Preoperative Neoadjuvant Therapy
Preoperative neoadjuvant therapy (or treatment administered before surgery) for early-stage triple-negative breast cancer has become a standard because it “provides valuable prognostic information, it gives opportunity to evaluate newer therapies and it helps inform the decisions we have to make after surgery,” said Isakoff.
The question remained controversial, Isakoff said, as to whether Carboplatin should be added to routine neoadjuvant therapy for triple-negative breast cancer to achieve pathological complete response rate (the lack of all signs of cancer in tissue samples removed during surgery or biopsy after treatment).
Phase 3 data confirming a long-term benefit are lacking, and phase 2 data show conflicting long-term benefit. There are no metastatic data that shows an overall survival benefit. Although it did increase toxicity in patients, many required a dose reduction or delay, the long-term toxicity is unaware and patients may be over treated because “you saw that about half of the patients already will have a complete response without the Carboplatin,” said Isakoff.
Results from the Keynote522 and Impassion031 studies both demonstrated that the addition of immunotherapy significantly improved the pathological complete response rate.
Side effects include hypothyroidism, skin reaction, hyperthyroidism, adrenal insufficiency (adrenal glands that don’t produce enough hormones) and inflammation of the lung tissue, colon, thyroid and liver.
“We need to better use the full power of preoperative therapy to optimize our therapy based on predictors of response,” said Isakoff.
Therapy for Advanced Triple-Negative Breast Cancer
“Previously, overall survival with triple-negative metastatic disease was about 12 to 15 months, and … now, thanks to some of the newer therapies including immunotherapy and Trodelvy (sacituzumab govitecan), it’s been extended now likely to over two years, although we don’t have rate numbers,” said Isakoff.
In the phase 3 Impassion 130 study, results demonstrated that the addition of Tecntriq (atezolizumab) significantly improved progression free survival in patients who had high expression of the PD-L1 marker, increasing from a median of five to seven and a half months. Overall survival was also improved with the addition of Tecntriq from about 18 to 25 months.
Patients with high expression of PD-L1, in Keynote 355, also showed improvement in progression free survival when treated with Keytruda (pembrolizumab).
The phase 3 ASCENT study showed results that progression free survival was improved for patients with triple-negative breast cancer when treated with Trodelvy, from 1.7 months to 5.6 months. As well as overall survival, which improved from 6.7 months to 12.1 months.
“We’ve made great progress with triple-negative breast cancer with some new drug approvals, but it still remains challenging with high risk,” said Isakoff. He added that there is still work to be done to determine optimum preoperative regimen for long-term benefit, optimum biomarkers to select which patients receive which drugs and which chemotherapy is the best to pair with immunotherapy.
“The future is much brighter today, I think, than it was several years ago (for triple-negative breast cancer),” he concludes.
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