Anti-PD-1/anti-LAG-3 combination highly effective in HER2-negative breast cancer

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

Addition of anti-PD-1 therapy to neoadjuvant chemotherapy has 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 shown to significantly improve progression-free survival [2]. The neoadjuvant I-SPY 2 trial (NCT01042379) evaluated the efficacy and safety of the addition of the anti-PD-1 antibody cemiplimab plus the anti-LAG-3 antibody fianlimab to neoadjuvant treatment with paclitaxel. Prof. Claudine Isaacs (Georgetown University Medical Center, DC, USA) presented the results [3].

A total of 76 patients with HER2-negative, treatment-naïve breast cancer received neoadjuvant treatment with paclitaxel/cemiplimab/fianlimab for 12 weeks; 350 patients treated with paclitaxel alone served as a control. 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 addition, the residual cancer burden class was downshifted across all subtypes. RCB 0/1 class was 37% in the control arm versus 64% in the study arm in all patients, 48% versus 70% for TNBC patients, and 29% versus 60% for HR-positive/HER2-negative patients.

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 TNBC patients with a positive ImPrint score was 82% when treated with paclitaxel/cemiplimab/fianlimab compared with 32% in TNBC patients with a negative ImPrint score. The pCR rate in HR-positive/HER2-negative patients with a positive ImPrint score was 91% when treated with paclitaxel/cemiplimab/fianlimab compared with 28% in HR-positive/HER2-negative patients with a negative ImPrint score. Addition of fianlimab and cemiplimab to paclitaxel was associated with an increased incidence of immune-related adverse events as well as 3 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 Prof. Isaacs. “In addition, the ImPrint signature identified patients with the greatest benefit from checkpoint inhibitor-based therapy.”

1. Schmid P, et al. N Engl J Med 2022;386:556–567.
2. Tawbi HA, et al. N Engl J Med. 2022;386:24–34.
3. Isaacs C, et al. Evaluation of anti-PD-1 cemiplimab plus anti-LAG-3 REGN3767 in combination with paclitaxel in early-stage, high-risk HER2-negative breast cancer: results from the Neoadjuvant I-SPY 2 trial. Abstract GS5-03, SABCS 2022, 6–10 December, San Antonio, TX, USA.
4. Mittempergher L, et al. J Clin Oncol. 2022;40(suppl):514–514.

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Posted on 1 February 202327 March 2024