MSD’s anti-PD-1 therapy Keytuda (pembrolizumab) won expanded indication to be used as neoadjuvant therapy in combination with chemotherapy before surgery in patients with triple-negative breast cancer (TNBC) and then continued as a single agent after surgery.
This indication allows Keytruda to treat not only metastatic but early TNBC.
On Wednesday, the Ministry of Food and Drug Safety authorized Keytruda as neoadjuvant therapy in combination with chemotherapy (carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide) before surgery. It continued as monotherapy after surgery in stage 2 and stage 3 TNBC patients who have not received prior treatment.
The indication does not require a PD-L1 expression test, giving benefits to more breast cancer patients.
Also, the government approved using Keytruda every three weeks and every six weeks before or after surgery, which is expected to improve patient convenience.
In July last year, Keytruda obtained the permit as combination therapy with chemotherapy to treat locally recurrent unresectable or metastatic TNBC with positive PD-L1 expression.
The latest indication allows Keytruda to treat both early and metastatic TNBC.
To raise survival and prevent relapse in TNBC, MSD set pre-operative and post-operative adjuvant therapy as “one treatment strategy.”
Usually, neoadjuvant therapy before surgery aims to raise complete pathological response (pCR) in the short term to increase event-free survival (EFS) and overall survival (OS). Along with postoperative adjuvant therapy, it aims to prevent metastasis and recurrence.
The latest nod was based on the phase 3 KEYNOTE-522 trial in 1,174 TNBC patients.
The study outcome showed that the Keytruda-chemotherapy combination group had a 37 percent lower risk of disease progression that precluded definitive surgery, a local or distance recurrence, a second primary cancer, or death from any cause compared to the chemotherapy alone group.
The study also demonstrated that Keytruda prolonged the EFS significantly.
The EFS in the third year was 84.5 percent in the treatment group vs. 76.8 percent in the control group.
At the median follow-up of 15.5 months, the Keytruda group’s PCR was 64.8 percent, much higher than 51.2 percent of the control group.
The safety profile was similar to chemotherapy and Keytruda monotherapy in patients with high-risk early TNBC. The study did not report any new safety issues.
Most immune-mediated adverse reactions occurred in neoadjuvant therapy before surgery, and those appearing in post-operative therapy were low-grade and manageable.
Based on the study results, the U.S. National Comprehensive Cancer Network (NCCN) recommends Keytruda adjuvant therapy before and after surgery as a category 2A preferred regimen for high-risk TNBC patients in the 2022 breast cancer treatment guideline.
The American Society of Clinical Oncology (ASCO) also recommended Keytruda adjuvant therapy before and after surgery for high-risk early TNBC in the latest 2022 guideline.
Kim Sung-phil, business unit head of the oncology franchise at MSD Korea, said he was pleased to introduce new therapy to NSBC patients one year after winning Keytruda’s first indication in breast cancer.
“Keytruda is the first combination of adjuvant therapy before and after surgery in one therapy for the first time in TNBC. As a result, reducing tumor size before surgery and preventing recurrence and metastasis after surgery will be new hope for high-risk early TNBC patients,” he said.