Neoadjuvant Atezolizumab Plus Epirubicin Shows Safety, Efficacy in Treatment of HER2+ Early Breast Cancer

Neoadjuvant atezolizumab (Tecentriq; Roche) plus epirubicin (Ellence; Pfizer) demonstrated its potential as a combination regimen for patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC) in the randomized phase 2 trial ABCSG-52 (EudraCT no. 2019-002364-27). These data support the rationale for combining immune checkpoint inhibitors with anthracycline-based chemotherapy.¹

Breast cancer cells | Image Credit: © Jack - stock.adobe.com

HER2+ breast cancer (BC) subtypes are aggressive and challenging to treat, calling for innovative, multifaceted therapeutic approaches. Chemotherapy and immunotherapies have greatly improved outcomes for patients, but there is a persistent need for therapies that offer patients better progression-free survival, overall survival, treatment response, and safety. Combination regimens have become crucial for addressing the complex nature of advanced disease, such as HER2+ EBC.

Atezolizumab is a PD-L1 monoclonal antibody that demonstrated efficacy and safety as a monotherapy and in combination with anthracycline-based chemotherapy across multiple studies. It received FDA approvals for various disease types including non–small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. As of January 2025, it is not approved in the United States for treatment of HER2+ EBC; however, it is approved by the European Medicines Agency for the treatment of PD-L1 immune cell-positive metastatic triple-negative BC.^2,3

In the ABCSG-52 trial, the researchers showed that a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab (Herceptin; Genentech), pertuzumab (Perjeta; Genentech), atezolizumab, and epirubicin was a safe and efficacious treatment for patients with HER2+ EBC. The study included 58 patients who were randomized 1:1 to receive 2 cycles of a chemotherapy-free induction phase of dual HER2 blockade with either trastuzumab and pertuzumab (TP) plus atezolizumab (TP-A; n=29) or TP alone (n=29), which was part 1 of the study. During part 2, patients received 4 cycles of TP-A in combination with epirubicin.²

The trial’s primary end point was pathological complete response (pCR), which is indicated as an effective metric to determine long-term patient outcomes associated with neoadjuvant treatment. The secondary end point was residual cancer burden (RCB).²

PCR was met in 35 patients (60.3%; 95% confidence interval (CI) 47.5% to 71.9%), which included 19 (65.5%) from the TP-A group and 16 patients (55.2%) from the TP group. The RBC and objective response rates in the TP-A and TP groups were 80.0% (n = 44/55; 95% CI 67.6% to 88.4%) and 89.3% (n = 50/56; 95% CI 78.5% to 95.0%), respectively.²

Grade ≥3 treatment-related adverse events (AE) were reported in 17 patients (29.3%), 9 patients (31.0%) in the TP-A group and 8 patients (27.6%) in the TP group. The most common AEs in both treatment arms were diarrhea (59% in TP-A, 62% in TP), fatigue (48% in TP-A, 59% in TP) and alopecia (41% in TP-A, 28% in TP; Table 3).²

"Our study shows that the combination of immunotherapy and weakened chemotherapy could be a promising yet gentle treatment option for patients with HER2-positive breast cancer," Gabriel Rinnerthaler of the Med Uni Graz Division of Oncology, said in a news release. “The trial results underscore the potential for modern immunotherapy to optimize breast cancer treatment—through improved effectiveness while easing the burden on patients. The knowledge obtained from the ABCSG52/ATHENE trial supports new approaches for personalized and innovative developments in breast cancer treatment.”⁴

REFERENCES

1. An open-label, two-arm, randomized, single-stage phase II study of ATezolizumab in combination with dual HER2 blockade plus epirubicin as NEoadjuvant therapy for HER2-positive early breast cancer. November 28, 2019. Accessed January 23, 2025. https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-002364-27/AT

2. Drugs.com. Tecentriq FDA approval history. December 19, 2022. Accessed January 23, 2025. https://www.drugs.com/history/tecentriq.html

3. Rinnerthaler G, Egle D, Bartsch R, et al. Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52/ATHENE trial. Nat Cancer. January 16, 2025. doi:10.1038/s43018-024-00890-2

4. New approaches in breast cancer treatment: combined chemotherapy and immunotherapy show promising results. News release. Med Uni Graz. January 22, 2025. Accessed January 23, 2025. https://www.medunigraz.at/en/news-1/detail/brustkrebsbehandlung-vielversprechende-ergebnisse-bei-innovativer-kombination#