Keytruda Rebounds in TNBC and Wins Approval for High-Risk, Early-Stage Patients

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After an earlier rejection from the U.S. Food and Drug Administration (FDA), Merck's. vaunted checkpoint inhibitor Keytruda finally won approval for treatment of patients with high-risk, early-stage triple-negative breast cancer. The approval marked the 30th for Keytruda.

Keytruda, an anti-PD-1 therapy, was approved in combination with chemotherapy based on data from a Phase III study that showed the pairing prolonged event-free survival (EFS). Keytruda, combined with carboplatin and paclitaxel as a neoadjuvant treatment before surgery, followed by doxorubicin or epirubicin and cyclophosphamide after the procedure, provided a statistically significant improvement in EFS compared to the same neoadjuvant chemotherapy regimens alone in patients with previously untreated stage II or stage III TNBC. 

In the KEYNOTE-522 study, Keytruda and the chemotherapy combination demonstrated a 37% reduction in the risk of disease progression that precluded definitive surgery, a local or distant recurrence, a second primary cancer, or death from any cause. Keytruda is the first anti-PD-1 therapy to show a statistically significant improvement in EFS as neoadjuvant and adjuvant therapy for TNBC.

Vicki Goodman, vice president of Clinical Research at Merck Research Laboratories, noted that triple-negative breast cancer is a common cancer in the United States, particularly in younger women and African American women, and also one of the most difficult to treat. With the FDA approval, Goodman said there is a new treatment option for this challenging cancer type.

“This neoadjuvant and adjuvant combination with KEYTRUDA is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community,” Goodman said in a statement.

In March, the FDA issued a Complete Response Letter after an advisory committee sought more long-term data in high-risk early-stage triple-negative breast cancer.

Breast cancer is the most common cancer among women. In triple-negative breast cancer, tumor cells lack hormone receptors and do not have excess HER2 protein. It is estimated that about 15% of breast cancers are triple-negative.

In an explanation of how tricky this type of cancer can be to treat, Joyce O’Shaughnessy, chair of Breast Cancer Research at Baylor University Medical Center, said that even when triple-negative breast cancer is diagnosed, between 30% and 40% of patients will see a recurrence of their cancer following standard neoadjuvant chemotherapy and surgery. Because of that statistic, there is a high unmet need for new treatment options for this kind of cancer. O’Shaughnessy said the latest FDA approval for the Keytruda -and- chemotherapy combination has the potential to change the treatment paradigm for this kind of cancer.

Keytruda could well be on its way to winning approval for another indication in breast cancer. This morning, Merck announced positive data from another Phase III study with the anti-PD-1 therapy. Data from the KEYNOTE-355 trial assessing Keytruda and chemotherapy in metastatic triple-negative breast cancer showed the combination demonstrated a statistically significant and clinically meaningful improvement in overall survival when compared with chemotherapy alone in patients with this type of cancer who have tumors that express PD-L1. 

Given the trickiness of treating triple-negative breast cancer, Goodman said the worst survival prognosis is metastatic triple-negative breast cancer. She said the new overall survival results confirm that Keytruda in combination with chemotherapy “represents an important treatment option for certain patients with metastatic TNBC.”

Merck said it would present the overall survival results at a future conference. The overall survival results were announced this morning following an earlier interim analysis that showed Keytruda and chemotherapy significantly improved progression free survival compared with chemotherapy alone in these patients. In the U.S., Keytruda is currently approved in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1. 


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