Keytruda Plus Chemo Increases Percentage of TNBC Patients With No Cancer Signs, Interim Analysis Shows

Using Keytruda (pembrolizumab) in combination with chemotherapy increased the percentage of patients showing no signs of breast cancer after completing a course of neoadjuvant therapy — treatment to shrink a tumor — and  surgery, interim analysis of a Phase 3 trial shows.

This marks the first time this type of therapy plus chemotherapy has demonstrated a statistically significant improvement in treating triple-negative breast cancer, the researchers said.

Keytruda is a checkpoint blockade immunotherapy developed by Merck (known as MSD outside the U.S. and Canada), which has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treating several types of cancer.

It is a monoclonal antibody that has been designed to target and block the activity of the PD-1 receptor — a protein found on the surface of immune cells — preventing cancer cells from avoiding being targeted and killed by immune cells. Monoclonal antibody treatments enlist the body’s natural immune system functions to fight cancer.

The ongoing randomized, double-blind, KEYNOTE-522 Phase 3 trial (NCT03036488) is assessing the safety and efficacy of Keytruda, versus a placebo, in combination with chemotherapy in 1,174 people with triple-negative breast cancer (TNBC).

In the first part of the study, participants are randomly assigned to receive either Keytruda in combination with chemotherapy, or a placebo plus chemotherapy as a neoadjuvant therapy for approximately 24 weeks (eight cycles). Neoadjuvant therapy aims to reduce the tumor burden before it’s removed by surgery.

After completing a course of neoadjuvant therapy, participants undergo definitive surgery, followed by an additional treatment with Keytruda or a placebo as an adjuvant therapy for approximately 27 weeks (nine cycles).

The trial has two different primary endpoints:

• Determine the percentage of patients showing no signs of cancer in tissue samples collected after completing a course of neoadjuvant therapy followed by surgery (pathological complete response, or pCR)
• Determine the time from the start of the treatment to disease progression before surgery, local or distant cancer recurrence, the formation of a second primary tumor, or death by any cause (event-free survival, or EFS)

According to data from an interim analysis of the trial, performed by an Independent Data Monitoring Committee (IDMC), the pCR primary endpoint of the study has been successfully completed.

Key findings from that analysis showed that patients treated with Keytruda had a statistically significant improvement in pCR rates compared with those treated with a placebo, regardless of having PD-L1-positive tumors or not.

Keytruda’s safety profile also was consistent with previous findings, with no new safety issues reported.

“These findings from this innovatively designed trial with Keytruda mark the first time an anti-PD-1 therapy plus chemotherapy has demonstrated a statistically significant improvement in pathological complete response rate as a neoadjuvant, or pre-surgical, segment of treatment for triple-negative breast cancer,” Roger M. Perlmutter, president of Merck Research Laboratories, said in a press release.

“TNBC is an aggressive malignancy with a high rate of recurrence within the first five years of diagnosis. We are encouraged by these results and plan to discuss these data with health authorities and to present these findings at an upcoming medical congress,” Perlmutter said.

Based on the feedback from the IDMC, KEYNOTE-522 will continue without alterations to its design to evaluate the event-free survival endpoint as planned.

Other Phase 3 trials are currently underway, including KEYNOTE-355 (NCT02819518) and KEYNOTE-242 (NCT02954874). Those trials are examining the therapeutic potential of Keytruda in combination with chemotherapy agents for TNBC.