According to results from the phase 3 APTneo Michelangelo study, the addition of atezolizumab to chemotherapy plus trastuzumab and pertuzumab did not significantly increase the pathological complete response (pCR) rate among patients with HER2-positive breast cancer.

The standard of care for patients with high-risk HER2-positive breast cancer is trastuzumab and pertuzumab plus chemotherapy. Luca Gianni, MD, Fondazione Michelangelo, Milan, Italy, and coatuhors wrote, “Compelling data show the contribution of the immune system in prognosis and response/resistance to HER2 directed therapies, supporting combination of immune checkpoint inhibitors with anti HER2 antibodies.”

This multicenter, open label, phase 3 trial enrolled 661 patients with high-risk early and locally advanced HER2-positive breast cancer. Patients were randomized to receive either neoadjuvant trastuzumab and pertuzumab plus chemotherapy alone (arm A; n = 223) or with 1200 mg atezolizumab (arm B; n = 438). Chemotherapy in the control arm consisted of carboplatin and paclitaxel for 6 cycles. Within the atezolizumab arm, patients were randomized to receive either anthracycline plus cyclophosphamide for 3 cycles followed by carboplatin and paclitaxel for 3 cycles (arm B1; n = 218), or carboplatin plus paclitaxel for 6 cycles (arm B2; n=220). Following surgery, patients continued with HER2-directed therapies, either with or without atezolizumab for up to 1 year. The primary end point of this study was the event-free survival of the control arm vs the atezolizumab arm. A key secondary end point was the rate of pCR with and without atezolizumab.

In arm B, the pCR rate was 57.8% compared with 52.0% in arm A, which did not represent a significant increase (hazard ratio: 1.33; 95% confidence interval, 0.95 to 1.86; P = .091). The difference in pCR rate between the arm B1 and arm B2 was not significant either. However, when compared to arm A, arm B1 had a significantly higher pCR rate. This difference was consistent regardless of HR or PD-L1 status.

Dr Gianni et al concluded, “Addition of atezolizumab to chemotherapy and [trastuzumab plus pertuzumab] did not significantly increase the rate of pCR in women with HER2[-positive breast cancer].” Though, he added, “An exploratory analysis showed that adding atezolizumab to neoadjuvant [anthracycline and cyclophosphamide] followed by [carboplatin and paclitaxel] led to higher pCR rate. This could be because of anthracyclines themselves or to drug-drug enhancement of anthracyclines and immune modulation.”

Source:

Gianni L, Munzone E, Mansutti M, et al. Pathologic complete response (pCR) of neoadjuvant therapy with or without atezolizumab in HER2-positive, early high-risk and locally advanced breast cancer: APTneo Michelangelo randomized trial. Presented at San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, Texas. Abstract LBO1-02