Merck's Keytruda Receives FDA Approval for PD-L1-Positive Triple-Negative Breast Cancer

November 15, 2020 News /BioValleyBIOON/ -- Merck & Co. recently announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to the anti-PD-1 therapy Keytruda (brand name: Keytruda; generic name: pembrolizumab), in combination with chemotherapy, for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer expressing PD-L1 (Combined Positive Score [CPS] ≥10)Breast Cancer(TNBC) patients. TNBC is a difficult-to-treat malignantTumor, approximately 15-20% of breast cancer patients areDiagnosisTNBC.

It is worth mentioning that,This marks the first approval of Keytruda in the field of breast cancer, as well as the 27th regulatory approval for Keytruda in the United States.Currently, another supplemental Biologics License Application (sBLA) for Keytruda in the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) is under review by the U.S. FDA. Specifically, this application seeks approval for the use of Keytruda in combination with chemotherapy as neoadjuvant treatment prior to surgery, followed by Keytruda as monotherapy for adjuvant treatment post-surgery.FDAThe PDUFA target date for this sBLA has been set as March 29, 2021.

Roy Baynes, M.D., Senior Vice President of Merck Research Laboratories and Global Head of Clinical Development, as well as Chief Medical Officer, stated: “Today’s approval marks a significant milestone, as it represents the first approval of Keytruda in the field of breast cancer. In the studies supporting this approval, Keytruda in combination with paclitaxel, nab-paclitaxel, or gemcitabine/carboplatin significantly improved outcomes compared to chemotherapy regimens alone.”TumorProgression-Free Survival in Patients with Advanced Triple-Negative Breast Cancer Expressing PD-L1 (CPS ≥ 10).

This approval is based on data from the Phase III KEYNOTE-355 study (NCT02819518). This was a randomized, double-blind trial conducted in 847 patients with locally recurrent, unresectable, or metastatic triple-negative breast cancer (TNBC) who had not previously received chemotherapy for metastatic disease. In the study, patients were randomized (2:1) to receive Keytruda plus chemotherapy or placebo plus chemotherapy, with all agents administered via intravenous infusion. The chemotherapy regimens used in the study consisted of one of the following three options: nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin.

Data show that, inTumorIn patients expressing PD-L1 with a Combined Positive Score (CPS) ≥10 (accounting for 38% of the study population), the Keytruda plus chemotherapy group demonstrated a statistically significant 35% reduction in the risk of disease progression or death compared to the placebo plus chemotherapy group (HR=0.65; 95% CI: 0.49–0.86; p=0.0012), along with a statistically and clinically significant prolongation of progression-free survival (PFS) (median PFS: 9.7 months vs. 5.6 months).

Furthermore, the objective response rate (ORR) in the Keytruda plus chemotherapy group was 53% (complete response rate [CR], 17%; partial response rate [PR], 36%), compared with 40% in the placebo plus chemotherapy group (CR, 13%; PR, 27%). The median duration of response (DOR) was 19.3 months in the Keytruda plus chemotherapy group and 7.3 months in the placebo plus chemotherapy group. In this study, the median duration of treatment with Keytruda was 5.7 months.

As previously stated, in accordance with the recommendation of the Independent Data Monitoring Committee (DMC), the study will continue without any modifications to evaluate another dual primary endpoint, overall survival (OS).

Keytruda belongs to the class of anti-PD-(L)1 cancer immunotherapies, which help detect and combat tumor cells by enhancing the body’s immune system capabilities. Keytruda is an anti-PD-1 therapy that activates potential effects by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2.TumorT lymphocytes of cells and healthy cells. To date, Keytruda has been approved for the treatment of more than 10 types of cancer.

Globally, more than 10 anti-PD-(L)1 therapies have been approved for market launch, with Keytruda emerging as the frontrunner. In 2019, its global sales reached $11.1 billion, representing a year-on-year growth of 58%.

Previously, the pharmaceutical market research firm EvaluatePharma released a report predicting that Keytruda’s sales would reach $24.91 billion in 2026, making it the world’s best-selling drug. Meanwhile, Bristol-Myers Squibb’s anti-PD-1 therapy Opdivo (Opdivo, nivolumab) is also projected to achieve sales of $12.677 billion, becoming the second best-selling drug globally.

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 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 exhibits a 5-year survival rate of less than 15%. TNBC is unresponsive to hormonal therapy and HER2-targeted therapies (such as Herceptin), resulting in very limited clinical treatment options that rely primarily on chemotherapy. Metastatic TNBC is among the most aggressive and difficult-to-treat forms of breast cancer.

Regarding new drugs for TNBC, in March 2019, the United StatesFDAApproval was granted for Roche’s anti-PD-L1 therapy Tecentriq (atezolizumab) in combination with chemotherapy (Abraxane) as a 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 for the treatment of PD-L1-positive metastatic TNBC. In the Phase III IMpassion130 study, compared with the placebo plus Abraxane regimen, the Tecentriq plus Abraxane regimen significantly reduced the risk of disease progression or death by 40% 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) and demonstrated a clinically meaningful 7-month improvement in overall survival (OS) (median OS: 25.0 vs. 18.0 months; HR=0.71, 95% CI: 0.54–0.93).

In April this year, the U.S. FDA approved Immunomedics’ antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy) for adult patients with metastatic triple-negative breast cancer (mTNBC) who had previously received at least two prior therapies for metastatic disease. Notably, Trodelvy is the first ADC approved by the FDA specifically for the treatment of relapsed or refractory mTNBC, and alsoFDAThe first approved anti-Trop-2 ADC drug. Data from the single-arm, multicenter Phase II IMMU-132-01 study showed that in heavily pretreated adult patients with metastatic triple-negative breast cancer (mTNBC) who had previously received multiple therapies (range: 2–10 regimens) for metastatic disease, Trodelvy treatment achieved an objective response rate (ORR) of 33.3% (95% CI: 24.6, 43.1) and a median duration of response (DOR) of 7.7 months (95% CI: 4.9, 10.8). (Bioon.com)

Original Source:FDA approves Merck’s KEYTRUDA® (pembrolizumab) in Combination With Chemotherapy for Patients With Locally Recurrent Unresectable or Metastatic Triple‑Negative Breast Cancer Whose Tumors Express PD-L1 (CPS ≥10)