Merck's Keytruda Plus Chemotherapy Significantly Improves Pathological Complete Response Rate in Phase III Trial for Triple-Negative Breast Cancer

July 30, 2019 News /BioValleyBIOON/ -- Oncology immunotherapy giant Merck & Co. recently announced the evaluation of PD-1TumorImmunotherapy Keytruda (Keytruda, generic name: pembrolizumab) combined with chemotherapy for the treatment of triple-negative breast cancerBreast CancerThe Phase III clinical study KEYNOTE-522 (NCT00336488) in patients with (TNBC) atAfter Neoadjuvant Therapy in Neoadjuvant/Adjuvant Study ProtocolsAchieved pathological complete response (pCR), one of the two primary endpoints. Notably, based on the study data, Keytruda is the first anti-PD-1 therapy to demonstrate a statistically significant improvement in pCR as a neoadjuvant treatment for triple-negative breast cancer (TNBC), regardless of PD-L1 status.

KEYNOTE-522 is a randomized, double-blind, Phase III study investigating Keytruda in combination with chemotherapy versus placebo in combination with chemotherapy as neoadjuvant therapy, followed by Keytruda versus placebo as adjuvant therapy, for the treatment of patients with triple-negative breast cancer (TNBC). The two primary endpoints are pathological complete response rate (pCR) and event-free survival (EFS). Secondary endpoints include pCR defined by other criteria at the time of definitive surgery (e.g., absence of residual invasive or non-invasive carcinoma in the breast or lymph nodes),TumorEFS, Overall Survival (OS), Safety, and Patient-Reported Outcomes in PD-L1–Expressing Patients

A total of 1,174 patients were enrolled in this study and randomized in a 2:1 ratio to receive one of the following two treatment regimens: (1) Keytruda (once every three weeks) plus paclitaxel (once weekly) and carboplatin (once weekly or once every three weeks) for four cycles, followed by Keytruda plus cyclophosphamide and doxorubicin or epirubicin (once every three weeks) for four cycles as neoadjuvant therapy prior to surgery, and then Keytruda (once every three weeks) for nine cycles as postoperative adjuvant therapy after surgery; (2)

Placebo (once every three weeks) + paclitaxel (once weekly) and carboplatin (once weekly or once every three weeks) for 4 cycles, followed by placebo + cyclophosphamide and doxorubicin or epirubicin (once every three weeks) for 4 cycles, and then placebo (once every three weeks) as postoperative adjuvant therapy for 9 cycles after surgery.

According to an interim analysis conducted by the Independent Data Monitoring Committee (DMC), Keytruda in combination with chemotherapy demonstrated a statistically significant improvement in pathological complete response (pCR) rates compared with chemotherapy alone, regardless of PD-L1 status. pCR is defined as the absence of any evidence of cancer in tissue samples analyzed after completion of neoadjuvant therapy and definitive surgery. Based on the DMC’s recommendation, the study will continue as originally designed without modifications, with evaluation of event-free survival (EFS) as one of the two primary endpoints. In this study, the safety profile of Keytruda was consistent with previously reported studies, and no new safety signals were identified.

Dr. Roger M. Perlmutter, President of Merck Research Laboratories, stated: “This innovative design from KeytrudaClinical TrialsThe results provided the first confirmation that anti-PD-1 therapy combined with chemotherapy, as a neoadjuvant or preoperative treatment for TNBC, demonstrated a statistically significant improvement in pCR. TNBC is an aggressive malignantTumor, the recurrence rate is high within the first five years after diagnosis. We are encouraged by these results and plan to discuss this data with regulatory authorities and present these findings at upcoming medical conferences.”

Keytruda’s clinical development program in breast cancer includes several internal and external collaborative studies, including three ongoing registrational studies supporting triple-negative breast cancer (TNBC) indications (KEYNOTE-355, KEYNOTE-242, and KEYNOTE-522).

Breast cancer is the most common type of cancer in women, with over 2 million new cases diagnosed globally each year. Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancers and is more prevalent in women under the age of 50 compared to other breast cancer subtypes. TNBC is specifically defined by the negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This aggressive form of breast cancer progresses rapidly, carries a very poor prognosis, has a high recurrence rate, and has a 5-year survival rate of less than 15%. TNBC does not respond to hormonal therapy or HER2-targeted therapies (such as Herceptin), leaving very limited clinical treatment options that primarily rely on chemotherapy. Metastatic TNBC is one of the most aggressive and difficult-to-treat forms of breast cancer.

It is worth mentioning that in March this year, the United StatesFDAAccelerated Approval of Roche’s PD-L1TumorTecentriq in Combination with Chemotherapy (Abraxane) as First-Line Treatment for Patients with PD-L1-Positive Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer (TNBC). This approval makes the Tecentriq plus Abraxane regimen the first cancer immunotherapy treatment for PD-L1-positive metastatic TNBC.

In the Phase III clinical trial IMpassion130, the Tecentriq plus Abraxane regimen significantly reduced the risk of disease progression or death by 40% compared with the placebo plus Abraxane regimen in PD-L1-positive patients (median PFS: 7.4 months vs. 4.8 months; HR=0.60, 95% CI: 0.48–0.77; p<0.0001). New data presented at the 2019 ASCO Annual Meeting showed that, compared with the placebo plus Abraxane regimen, the Tecentriq plus Abraxane regimen resulted in a clinically meaningful 7-month improvement in overall survival (OS) in PD-L1-positive patients (median OS: 25.0 vs. 18.0 months; HR=0.71, 95% CI: 0.54–0.93). (Bioon.com)

Original Source:MSD Website