In the Korean phase II Neo-PATH trial reported in JAMA Oncology, Ahn et al found that neoadjuvant treatment with atezolizumab, pertuzumab/trastuzumab, and docetaxel produced a pathologic complete response in 61% of patients with HER2-positive stage II/III breast cancer treated with the regimen.
Study Details
In the multicenter trial, 67 women enrolled between May 2019 and May 2020 received six cycles of atezolizumab at 1,200 mg, pertuzumab at 840 mg in the first cycle and at 420 mg in subsequent cycles, trastuzumab at 600 mg subcutaneously, and docetaxel at 75 mg/m2 every 3 weeks, followed by surgery. Patients with a pathologic complete response received 12 cycles of adjuvant atezolizumab, trastuzumab, and pertuzumab every 3 weeks; those without a pathologic complete response received 14 cycles of atezolizumab at 1,200 mg and trastuzumab emtansine at 3.6 mg/kg every 3 weeks. The primary endpoint was pathologic complete response rate.
Pathologic Complete Response Rate
A pathologic complete response was achieved in 41 of the 67 patients (61%), including 27 of 35 hormone receptor (HR)-negative (77%) vs 14 of 32 HR-positive patients (44%) and in 13 of 13 PD-L1–positive (≥ 1% immune cells) (100%) vs 28 of 53 PD-L1–negative patients (53%).
KEY POINTS
- Pathologic complete response was achieved in 61% of patients.
- Pathologic complete response was achieved in 77% of HR-negative vs 44% of HR-positive patients and in 100% of PD-L1–positive vs 53% of PD-L1–negative patients.
Clinical objective response was achieved in 63 patients (94%), with complete response in 30 (45%). An additional two patients had stable disease.
Adverse Events
During neoadjuvant treatment, grade 3 or 4 adverse events occurred in 31% of patients, most commonly neutropenia (12%), febrile neutropenia (8%), and alanine aminotransferase elevation (3%). Serious adverse events occurred in 19%, most commonly febrile neutropenia (6%). The most common immune-mediated adverse events of any grade were rash (64%) and fever (30%); four grade 3 events were observed (rash, encephalitis, hepatitis, and fever). No treatment-related deaths occurred.
The investigators concluded: “In this nonrandomized clinical trial, treatment with the neoadjuvant atezolizumab, docetaxel, trastuzumab, and pertuzumab regimen in patients with stage II or III [HER2]-positive breast cancer appears to have had an acceptable pCR rate and modest toxic effects. Further investigation of this immunotherapy combination in [HER2]-positive early breast cancer is warranted.”
Yeon Hee Park, MD, PhD, of Samsung Medical Center, Sungkyunkwan University School of Medicine, and Kyung Hae Jung, MD, PhD, of Asan Medical Center, University of Ulsan College of Medicine, Seoul, are the corresponding authors for the JAMA Oncology article.
Disclosure: The study was supported by the Ministry of Health and Welfare, Republic of Korea, and others. For full disclosures of the study authors, visit jamanetwork.com.
