Pembrolizumab and Chemotherapy Met Primary Endpoint in Phase III TNBC Trial

Roger M. Perlmutter, MD, PhD

Roger M. Perlmutter, MD, PhD

The combination of pembrolizumab (Keytruda) with chemotherapy demonstrated a benefit in terms of pathological complete response (pCR) when used as neoadjuvant therapy compared with chemotherapy alone in patients with triple-negative breast cancer (TNBC), according to interim results of the pivotal phase III KEYNOTE-522 trial. Merck announced in a press release that this met one of the dual-primary endpoints for the neoadjuvant/adjuvant study.

“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,” said Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, in the 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.”

The interim analysis also showed that the safety profile was consistent with prior reports of pembrolizumab and no new safety signals were found.

The ongoing registration-enabling study will continue without changes to the trial design based on the recommendation of the independent data monitoring committee to evaluate the other primary endpoint of event-free survival (EFS).

KEYNOTE-522 is a randomized, double-blind phase III trial that is assessing the anti—PD-1 therapy in combination with chemotherapy or chemotherapy alone as neoadjuvant therapy followed by pembrolizumab versus placebo as adjuvant therapy in patients with TNBC (NCT03036488).

Eligible patients had newly diagnosed, locally advanced, non-metastatic TNBC, adequate organ function, and an ECOG performance status of 0 or 1. Patients with an invasive malignancy diagnosed within the last 5 years, active autoimmune disease, HIV, or hepatitis B or C virus were excluded from entering the trial.

A total of 1174 patients were enrolled in the trial and randomized 2:1 to either the pembrolizumab-with-chemotherapy arm or the chemotherapy-alone arm. In the added pembrolizumab arm, patients received the immune checkpoint inhibitor every 3 weeks plus weekly paclitaxel and carboplatin, given either weekly or every 3 weeks, for 4 cycles. This was followed by pembrolizumab, cyclophosphamide, and doxorubicin or epirubicin every 3 weeks for 4 cycles prior to the patient undergoing surgery. After surgery, patients received 9 cycles of pembrolizumab every 3 weeks as adjuvant therapy.

In the chemotherapy/placebo arm, patients received placebo every 3 weeks plus weekly paclitaxel and carboplatin, given either weekly or every 3 weeks, for 4 cycles; then placebo, cyclophosphamide, and doxorubicin or epirubicin every 3 weeks for 4 cycles before surgery. Adjuvant therapy consisted of 9 cycles of placebo every 3 weeks.

Patients received definitive surgery 3 to 6 weeks after the last cycle of neoadjuvant therapy in both arms.

The dual primary endpoints were pCR and EFS, with pCR defined as having no evidence of disease in tissue samples following the completion of neoadjuvant therapy and definitive surgery. Secondary endpoints of the trial include EFS in patients with PD-L1 expression, overall survival, safety, and patient-reported outcomes.

Reference:

Merck’s KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy Met Primary Endpoint of Pathological Complete Response (pCR) in Pivotal Phase 3 KEYNOTE-522 Trial in Patients with Triple-Negative Breast Cancer (TNBC) [press release]. Kenilworth, NJ: Merck; July 29, 2019. https://bit.ly/330fv0I. Accessed July 29, 2019.