Paclitaxel/cemiplimab/fianlimab is a highly effective combination for neoadjuvant therapy in both triple-negative breast cancer (TNBC) and HR-positive/HER2-negative breast cancer. In addition, ImPrint signature identifies patients with the greatest benefit from checkpoint inhibitor-based therapy, results from I-SPY-2 showed.


The addition of anti-PD-1 therapy to neoadjuvant chemotherapy has been shown to significantly improve the pathologic complete response (pCR) and event-free survival in patients with TNBC.1 In melanoma, addition of an anti-LAG-3 antibody to anti-PD-1 therapy has been shown to significantly improve progression-free survival.2 To this end, the neoadjuvant I-SPY 2 trial evaluated the efficacy and safety of addition of the anti-PD-1 antibody cemiplimab plus the anti-LAG-3 antibody fianlimab to neoadjuvant treatment with paclitaxel. Dr. Claudine Isaacs (Georgetown University Medical Center) presented the results3 at the 2022 San Antonio Breast Cancer Symposium.

A total of 76 patients with HER2-negative, treatment-naïve breast cancer had neoadjuvant treatment with paclitaxel/cemiplimab/fianlimab for 12 weeks; 350 patients treated with paclitaxel alone served as a control. The addition of cemiplimab/fianlimab to paclitaxel increased the pCR rate: 44% versus 21% (all patients), 53% versus 29% (TNBC), and 36% versus 14% (HR-positive/HER2-negative). In line with this, the residual cancer burden (RCB) class was downshifted across all subtypes. RCB0-1 increased from 37% to 64% (all patients), from 48% to 70% (TNBC), and from 29% to 60% (HR-positive/HER2-negative).

ImPrint, a 53-gene signature of neoadjuvant immunotherapy response, has recently been developed.4 In the I-SPY-2 trial, a positive ImPrint score was able to identify patients with the greatest benefit from checkpoint inhibitor-based therapy. The pCR rate in patients with TNBC/ImPrint-positive score was 82% when treated with paclitaxel/cemiplimab/fianlimab compared with 32% in patients with a TNBC/ImPrint-negative score. The pCR rate in patients with a HR-positive/HER2-negative/ImPrint-positive score was 91% when treated with paclitaxel/cemiplimab/fianlimab compared with 28% in patients with HR-positive/HER2-negative/ImPrint-negative score. The addition of fianlimab to cemiplimab was associated with and increased incidence of immune-related adverse events as well as three cases (5%) of Type 1 diabetes.

“Paclitaxel/cemiplimab/fianlimab is a highly-effective combination for neoadjuvant therapy in both TNBC and HR-positive/HER2-negative breast cancer,” concluded Dr. Isaacs. “In addition, the ImPrint signature identified patients with the greatest benefit from checkpoint inhibitor-based therapy.”

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