Immuno-Oncology Resource Center

Immuno-Oncology Resource Center


Press Release

July 27, 2021
2 min read

FDA approves Keytruda for high-risk, early-stage triple-negative breast cancer


Press Release

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The FDA approved pembrolizumab for treatment of patients with high-risk, early-stage triple-negative breast cancer.

The approval applies to use of pembrolizumab (Keytruda, Merck) — an anti-PD-1 therapy — with chemotherapy in the neoadjuvant setting, then as monotherapy in the adjuvant setting.

The use of pembrolizumab with neoadjuvant platinum-based chemotherapy and as monotherapy in the adjuvant setting extended EFS among patients with early-stage triple-negative breast cancer.
Data derived from Schmid P, et al. Abstract 179. Presented at: ESMO Virtual Plenary; July 15, 2021.

“Even when triple-negative breast cancer is diagnosed early, 30% to 40% of patients will suffer cancer recurrence after standard neoadjuvant chemotherapy and surgery,” Joyce O’Shaughnessy, MD, chair of breast cancer research at Baylor University Medical Center and Texas Oncology, said in a Merck-issued press release. “Therefore, there is a high unmet need for new treatment options. [This] approval is very welcome news and has the potential to change the treatment paradigm by now including an immunotherapy as part of the regimen for patients with high-risk early-stage triple-negative breast cancer.”

The FDA based approval on results of the randomized phase 3 KEYNOTE-522 trial, which included 1,174 adults with previously untreated, nonmetastatic, centrally confirmed triple-negative breast cancer. All patients had stage T1c N1-2 or T2-4 N0-2 disease.

Researchers assigned 784 patients to 200 mg pembrolizumab every 3 weeks in combination with neoadjuvant chemotherapy (four cycles of paclitaxel and carboplatin, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide). The other 390 patients chemotherapy plus placebo.

All patients underwent definitive surgery and received radiation therapy as indicated. Depending on randomization, they received adjuvant pembrolizumab or placebo. Adjuvant treatment continued for up to nine cycles, or until disease recurrence or unacceptable toxicity.

Pathologic complete response — defined as ypT0/Tis ypN0, meaning clearance of the cancer from the breast after chemotherapy — and EFS served as dual primary endpoints. Secondary endpoints included OS, efficacy in the subset of patients with PD-L1-positive disease, and safety.

Results released in 2019 revealed a statistically significant improvement in pathologic complete response rate with pembrolizumab plus chemotherapy in the entire population (64.8% vs. 51.2%; P = .00055), the subgroup of patients with PD-L1-positive disease (68.9% vs. 54.9%) and the subgroup of those with PD-L1-negative disease (45.3% vs. 30.3%).

Results presented earlier this summer, based on median follow-up of 39.1 months, showed a statistically significant improvement in EFS in the pembrolizumab group.

At data cutoff, 123 patients (15.7%) assigned pembrolizumab and 93 patients (23.8%) assigned placebo had experienced EFS events (HR = 0.63; 95% CI, 0.48-0.82).

Median EFS had not been reached in either treatment group; however, researchers reported a higher 36-month EFS rate among patients assigned pembrolizumab (84.5% vs. 76.8%).

The most common EFS event was distant recurrence, experienced by 60 patients (7.7%) assigned pembrolizumab and 51 patients (13.1%) assigned placebo.

Follow-up for OS is ongoing. By data cutoff, 10.2% of patients who received immune therapy plus chemotherapy and 14.1% of those assigned chemotherapy alone had died. The OS difference between groups had not reached statistical significance (HR = 0.72; 95% CI, 0.51-1.02).

A comparable percentage of patients in the pembrolizumab and placebo groups experienced grade 3 or higher treatment-related adverse events (77.1% vs. 73.3%). A comparable percentage of patients each group experienced treatment-related adverse events that led to death (0.5% vs. 0.3%), though a higher percentage of patients assigned pembrolizumab experienced events that led to discontinuation of any drug (27.7% vs. 14.1%).

A considerably higher percentage of patients assigned pembrolizumab experienced immune-mediated adverse events (any grade, 43.6% vs. 21.9%; grade 3 to grade 5, 14.9% vs. 2.1%).