Merck’s Keytruda Helps Patients with High-Risk Breast Cancer

Merck recently announced that its anti-PD-1 therapy, Keytruda significantly helped patients with high-risk early-stage triple-negative breast cancer (TNBC)

The Phase 3 KEYNOTE-522 trial investigated Keytruda in combination with chemotherapy as pre-operative treatment, followed by a continued single agent treatment after surgery.

Overall, researchers found that the trial met its dual primary endpoint of event-free survival when compared with chemotherapy alone, as well as the secondary endpoint of pathological complete response.

“KEYTRUDA is the first immunotherapy to show positive results for event-free survival in patients with high-risk early-stage TNBC, a particularly aggressive form of breast cancer,” said Roy Baynes, MD, senior vice president and head of global clinical development at Merck Research Laboratories, said in the announcement. 

“The improvement in pathological complete response rates initially observed following pre-operative treatment was encouraging, and now that we are seeing the data mature after four years to include a statistically significant improvement in event-free survival, we look forward to working with the FDA and other global authorities to bring this new option to patients as quickly as possible,” said Baynes who also serves as chief medical officer at Merck’s laboratory research arm.

At the end of September, results from KEYNOTE-522 were published in the New England Journal of Medicine.

In the trial, researchers randomly assigned patients with previously untreated stage 2 or stage 3 TNBC to receive pre-operative therapy with four cycles of Keytruda at a dose of 200 milligrams every three weeks.

This therapy was combined with two chemotherapy medications—paclitaxel and carboplatin. 

The groups then received an additional four cycles of pembrolizymab or a placebo. The groups also received chemotherapies doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide.

Among the first 602 patients who underwent randomization, 64.8 percent in the pembrolizumab chemotherapy group and 51.2 percent of patients in the placebo-chemotherapy group elicited complete response. 

After a median follow-up of 15.5 months, 7.4 percent of patients in the pembrolizumab-chemotherapy group and 11.8 percent in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause. 

Merck then received a complete response letter from FDA in March 2021 regarding its supplemental biologics license application, which sought approval for Keytruda based on pathological complete response data and early interim event-free survival findings.

In the complete response letter, FDA’s Oncologic Drugs Advisory Committee voted 10 to 0 that a regulatory decision about Keytruda should be deferred until further data are available from KEYNOTE-522. 

The agency’s decision was based on pathological complete response data and early interim event-free survival findings from the trial. 

The Keytruda clinical development program for TNBC includes various internal studies and external collaborative trials. This includes ongoing studies KEYNOTE-242 and KEYNOTE-355.

Merck also has an expansive clinical development program investigating Keytruda in earlier lines of therapy including in pre-operative, a single agent, and locally advanced settings, with nearly 20 registrational studies ongoing.

TNBC makes up nearly 10 to 15 percent of all breast cancers. The five-year survival rate for this type of cancer is 90 percent. 

Aditya Bardia, MD, MPH, director of breast cancer research program at Mass General Cancer Center and assistant professor of medicine at Harvard Medical School, said in a statement that historically, women with TNBC have had very few effective treatment options and poor prognosis. 

But last month, Gilead announced that FDA approved Trodelvy for adults with unresectable, locally advanced, or metastatic TNBC. 

FDA based its approval on results from a Phase 3 study, ASCENT, in which Trodelvy demonstrated a statistically significant 57 percent reduction in the risk of disease worsening or death.

Additionally, the drug extended median overall survival to 11.8 months versus 6.9 months, representing a 49 percent reduction.