Neoadjuvant Atezolizumab, Trastuzumab, Pertuzumab,and Docetaxel Yields Acceptable pCR in ERBB2+ Breast Cancer

The phase 1/2 Neo-PATH trial show promising pathological complete response rates and moderate toxicity in patients with stage III or III ERBB2-positive breast cancer when treated with pertuzumab, atezolizumab, trastuzumab, and docetaxel.

A promising pathological complete response (pCR) rate and tolerable toxicity profile were observed in patients with stage II or III ERBB2-positive breast cancer who were treated with a quadruplet regiment of atezolizumab (Tecentriq), docetazel, trastuzumab (Enhertu), and pertuzumab (Perjeta), according to data from the phase 1/2 Neo-PATH trial (NCT03881878) published in JAMA Oncology.

In a population of 41 patients, the overall pathologic complete response (pCR) rate was 61% (90% CI, 50%-71%). Residual cancer burden of class I response was observed in 12% of patients, class II in 19%, and class III in 4%. Those who had stage IIA cancer had a pCR rate in 69%, 70% for those with stage IIB disease, and 39% for those who had stage III disease. The clinical objective response rate was 94.0%. In patients who had hormone receptor (HR)–negative disease, the pCR rate was 77% compared with 44% for those with HR-positive disease. In patients who had PD-L1 expression, the pCR rate was 100% vs 53% in those with no expression.

“The neoadjuvant atezolizumab combination PATH demonstrated a pCR rate worth further investigation, with fewer hematologic toxic effects with prevalent long-acting filgrastim [Neupogen] support,” investigators of the study wrote.

A total of 67 patients enrolled across 6 institutions in Korea. By data cutoff, all patients had completed neoadjuvant treatment. During neoadjuvant treatment, 2 patients experienced progressive disease and the remaining patients undergoing curative surgery, of whom 42 underwent breast-conserving surgery and 23 received a mastectomy. In 64 patients, R0 resection was achieved.

Treatment with pertuzumab was administered intravenously at a dose of 840 mg in the first cycle and 420 mg, thereafter; atezolizumab at 1200 mg intravenously; docetaxel at 75 mg/m2 intravenously; and 600 mg of trastuzumab subcutaneously every 3 weeks then followed by curative surgery.

Patients had a median age of 52 years, 48% had positive HR expression, and 52% had negative HR expression. Overall, 73% of patients had clinical stage II breast cancer.

Overall, the most common hematologic adverse effect (AE) was neutropenia in 13% of patients, with 12% having grade 3 or higher events. Moreover, 8% of patients experienced febrile neutropenia. Non-hematologic AEs included myalgia (75%), alopecia (67%), neuropathy (58%), diarrhea (51%), fatigue (40%), nausea (33%), and mucositis (31%). A total of 8% of patients experienced grade 3 or higher AEs.

Frequent immune-related AEs included skin rash (64%), fever (30%), thyroid dysfunction (10%), pneumonitis (9%), hepatitis (3%), and encephalitis (2%). Immune-related AEs of grade 3 or higher occurred in 6% of patients and included rash, fever, hepatitis, and encephalitis in 1 patient each.

Treatment discontinuation or interruption of atezolizumab occurred in 10% of patients. Treatment was not interrupted for pertuzumab or trastuzumab. Serious AEs occurred in 21% of patients, with the most common being febrile neutropenia (6%), fever (5%), and other immune-related AEs (3%). No patients died during the neoadjuvant portion of the study.

Reference

Ahn HK, Sim SH, Suh KJ, et al. Response rate and safety of a neoadjuvant pertuzumab, atezolizumab, docetaxel, and trastuzumab regimen for patients with ERBB2-positive stage II/III breast cancer: the Neo-PATH phase 2 nonrandomized clinical trial. JAMA Oncol. Published online July 7, 2022. doi:10.1001/jamaoncol.2022.2310