KEYNOTE-355 trial: Pembrolizumab in combination with chemotherapy met primary endpoint of progression-free survival as first-line treatment for metastatic triple-negative breast cancer with expression of PD-L1
The pivotal phase 3 KEYNOTE-355 trial investigating Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, in combination with chemotherapy met one of its dual primary endpoints of progression-free survival ( PFS ) in patients with metastatic triple-negative breast cancer ( mTNBC ) whose tumors expressed PD-L1 ( Combined Positive Score [ CPS ] greater than or equal to 10 ).
Based on an interim analysis conducted by an independent Data Monitoring Committee ( DMC ), first-line treatment with Pembrolizumab in combination with chemotherapy ( nab-Paclitaxel, Paclitaxel or Gemcitabine / Carboplatin ) has demonstrated a statistically significant and clinically meaningful improvement in PFS compared to chemotherapy alone in these patients.
Based on the recommendation of the DMC, the trial will continue without changes to evaluate the other dual primary endpoint of overall survival ( OS ).
The safety profile of Pembrolizumab in this trial was consistent with that observed in previously reported studies; no new safety signals were identified.
KEYNOTE-355 is a randomized, two-part, phase 3 trial evaluating Pembrolizumab in combination with one of three different chemotherapies compared with placebo plus one of the three chemotherapy regimens for the treatment of locally recurrent inoperable or mTNBC that has not been previously treated with chemotherapy in the metastatic setting.
Part 1 of the study was open-label and evaluated the safety and tolerability of Pembrolizumab in combination with either nab-Paclitaxel, Paclitaxel or Gemcitabine / Carboplatin in 30 patients.
Part 2 of KEYNOTE-355 was double-blinded, with dual primary endpoints of overall survival and progression free survival in all participants and in participants whose tumors expressed PD-L1 ( CPS greater than or equal to 1 and CPS greater than or equal to 10 ).
The secondary endpoints include 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 Pembrolizumab ( 200 mg intravenously [ IV ] on day 1 of each 21-day cycle ) plus nab-Paclitaxel ( 100 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle ), Paclitaxel ( 90 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle ) or Gemcitabine / Carboplatin ( 1,000 mg/m2 [ Gemcitabine ] and Area Under the Curve [ AUC ] 2 [ Carboplatin ] on days 1 and 8 of each 21-day cycle ); or placebo ( normal saline on day 1 of each 21-day cycle ) plus nab-Paclitaxel ( 100 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle ), Paclitaxel ( 90 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle ) or Gemcitabine / Carboplatin ( 1,000 mg/m2 [ Gemcitabine ] and AUC 2 [ Carboplatin ] on days 1 and 8 of each 21-day cycle ).
Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Triple-negative breast cancer is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis.
While some breast cancers may test positive for estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 ( HER2 ), TNBC tests negative for all three.
As a result, TNBC does not respond to therapies targeting these markers, making it more difficult to treat.
Approximately 15-20% of patients with breast cancer are diagnosed with TNBC. ( Xagena )
Source: Merck ( MSD ), 2020