Merck's KEYTRUDA in Combination with Chemotherapy Meets Primary Endpoint of Progression-Free Survival in First-Line Treatment of Metastatic Triple-Negative Breast Cancer

Source: Jike Yaowen

On February 12, MSD announced that Keytruda (pembrolizumab) in combination with chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin) met the primary endpoint of progression-free survival (PFS) in the pivotal Phase 3 KEYNOTE-355 clinical trial evaluating first-line treatment for metastatic triple-negative breast cancer (mTNBC) with PD-L1 expression [Combined Positive Score (CPS) ≥10]. Based on an interim analysis conducted by an independent Data Monitoring Committee (DMC), first-line treatment with Keytruda plus chemotherapy demonstrated a statistically and clinically significant improvement in PFS compared with chemotherapy alone. Per the DMC’s recommendation, the trial will continue to assess the other dual primary endpoint, overall survival (OS). MSD stated that it will engage with regulatory authorities regarding the trial data and present the study results at upcoming medical conferences.

Dr. Roger M. Perlmutter, President of Merck Research Laboratories, stated, “These are very encouraging results. Keytruda in combination with chemotherapy has demonstrated positive outcomes both as a first-line treatment for metastatic triple-negative breast cancer (TNBC) in the KEYNOTE-355 trial and as neoadjuvant therapy in the KEYNOTE-522 trial.”

MSD is conducting multiple internal and external collaborative clinical development programs on Keytruda for the treatment of breast cancer, including three ongoing registrational studies in triple-negative breast cancer (TNBC): KEYNOTE-355, KEYNOTE-242, and KEYNOTE-522. On July 29 last year, MSD announced that Keytruda in combination with chemotherapy, as a neoadjuvant therapy for triple-negative breast cancer, had met the primary endpoint of pathological complete response (pCR) in the Phase 3 KEYNOTE-522 clinical trial.

KEYNOTE-355 is a randomized, two-part Phase 3 clinical trial (NCT02819518) that evaluated Keytruda in combination with one of three different chemotherapy regimens (investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin) versus placebo plus one of the three chemotherapy regimens for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer (mTNBC) in patients who had not previously received chemotherapy for metastatic disease. Part 1 of the KEYNOTE-355 study was open-label and assessed the safety and tolerability of Keytruda combined with nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin in 30 patients. Part 2 of KEYNOTE-355 was a double-blind study that evaluated the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in all participants and in participants with PD-L1–expressing tumors (combined positive score [CPS] ≥1 and CPS ≥10). Secondary endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety. Part 2 of KEYNOTE-355 enrolled 847 patients, who were randomized to receive Keytruda plus nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin, or placebo plus one of the three chemotherapy regimens. The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies; no new safety signals were identified.

Triple-Negative Breast Cancer (TNBC) refers to a subtype of breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). It accounts for 10%–20% of all breast cancer pathological subtypes and predominantly affects premenopausal women. TNBC is the most aggressive form of breast cancer, characterized by high invasiveness, a propensity for metastasis, and a very poor prognosis. The median survival time after diagnosis is typically no more than 20 months, and the 5-year survival rate is less than 15%.

Keytruda is an anti-PD-1 therapy that has received FDA approval for the treatment of more than 10 cancer indications, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), head and neck cancer, hepatocellular carcinoma, and renal cell carcinoma. In July 2018, Keytruda (pembrolizumab) was approved in China for the treatment of unresectable or metastatic melanoma after failure of first-line therapy, becoming the first PD-1 inhibitor approved in China for the treatment of advanced melanoma. In March 2019, Keytruda in combination with pemetrexed and cisplatin was approved in China for the first-line treatment of EGFR- and ALK-negative metastatic non-squamous NSCLC. In October 2019, Keytruda monotherapy was approved for the first-line treatment of locally advanced or metastatic NSCLC in patients with PD-L1-positive tumors and no EGFR or ALK mutations. In November 2019, Keytruda in combination with carboplatin and paclitaxel was approved for the first-line treatment of metastatic squamous NSCLC.

References:

[1] Merck’s KEYTRUDA^® (pembrolizumab) in Combination with Chemotherapy Met Primary Endpoint of Progression-Free Survival (PFS) as First-Line Treatment for Metastatic Triple-Negative Breast Cancer (mTNBC). Retrieved 2020-02-12, from https://investors.merck.com/news/press-release-details/2020/Mercks-KEYTRUDA-pembrolizumab-in-Combination-with-Chemotherapy-Met-Primary-Endpoint-of-Progression-Free-Survival-PFS-as-First-Line-Treatment-for-Metastatic-Triple-Negative-Breast-Cancer-mTNBC/default.aspx

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