Dr Jain on Existing Challenges Within the TNBC Treatment Paradigm

“Unfortunately, triple-negative breast cancer is a more aggressive type of breast cancer, so [although] these new, novel treatments are doing better than the previous standard of care, they’re still not perfect. Trying to understand how to optimize treatments is still something that needs to be researched.”

Angela Jain, MD, associate professor, Department of Hematology/Oncology; interim chief, Division of Breast Medical Oncology; and chief, Division of Gynecologic Medical Oncology, Fox Chase Cancer Center, details some existing challenges with the triple-negative breast cancer (TNBC) treatment paradigm.

Novel treatments have started to show promise over previous standard of care for TNBC; however, these treatments still aren’t perfect due to the aggressiveness of the subtype, Jain begins. Now, an unmet need within the TNBC treatment paradigm is identifying and understanding optimal treatment options for the respective patient population, she says. Continuing to establish treatment combination strategies and developing more novel drugs could contribute to closing the gap with this disparity, she explains.

Nevertheless, recent studies have highlighted efforts toward identifying optimal treatment options. Of note, novel therapies, such as neoadjuvant camrelizumab plus intensive chemotherapy, have shown to significantly improve pathologic complete response (pCR) rates compared with chemotherapy alone in early or locally advanced TNBC. Data from the phase 3 CamRelief study (NCT04613674) revealed that patients who were treated with camrelizumab/intensive chemotherapy experienced a pCR rate of 56.8% vs 44.7% with chemotherapy alone.

Furthermore, determining biomarkers, including the T-cell inflamed 18-gene expression profile and tumor mutational burden, were associated with positive pCR rates and event-free survival in patients with high-risk, early-stage TNBC, according to the phase 3 KEYNOTE-522 study (NCT03036488). This was demonstrated in those who were treated with pembrolizumab (Keytruda) plus chemotherapy, although the biomarkers were not able to predict the efficacy benefit of pembrolizumab.

Determining nuanced differences in TNBC could also be a significant consideration, Jain emphasizes. An emerging paradigm shift in the TNBC landscape includes HER2-low disease, she notes. Jain concludes that this distinction could be crucial, as patients with HER2-low disease could be eligible for HER2-targeted agents such as fam-trastuzumab deruxtecan-nxki (Enhertu).