medwireNews: Almost two-thirds of patients with HER2-positive early breast cancer have a pathologic complete response (pCR) to neoadjuvant treatment with pertuzumab, atezolizumab, docetaxel, and trastuzumab (PATH), phase 2 study data show.
Writing in JAMA Oncology, Yeon Hee Park (Sungkyunkwan University School of Medicine, Seoul, South Korea) and co-authors say that use of the regimen in this population “warrants further investigation” in a large, randomized controlled trial.
The Neo-PATH study included 67 women (median age 52 years) with clinical stage II or III HER2-positive breast cancer from six institutions across South Korea. Between 2019 and 2020 they were given six cycles of neoadjuvant pertuzumab at a dose of 840 mg during the first cycle then 420 mg in subsequent cycles, atezolizumab 1200 mg, docetaxel 75 mg/m2, and trastuzumab 600 mg every 3 weeks, followed by surgery.
In addition, tripegfilgrastim 6 mg was administered 24 hours after each cycle at the discretion of the treating physician.
Following surgery, patients with a pCR received 12 cycles of adjuvant atezolizumab, trastuzumab, and pertuzumab every 3 weeks, while those without a pCR underwent 14 cycles of atezolizumab plus trastuzumab emtansine 3.6 mg/kg every 3 weeks.
The researchers report that, overall, the pCR was 61%, but the rate varied according to hormone receptor (HR) and PD-L1 expression.
Specifically, the pCR rate was 77% in the 35 patients with HR-positive disease and 44% in the 32 patients with HR-negative disease, while the pCR rate in PD-L1-positive (n=13) and -negative participants was 100% and 53%, respectively.
Just under a third (31%) of patients experienced a grade 3 or 4 adverse event (AE), most commonly neutropenia (12%) and febrile neutropenia (8%). Four (6%) patients experienced a grade 3 or 4 immune-related AE and there were no treatment-related deaths during neoadjuvant therapy.
Docetaxel dose modifications as a result of toxicity were needed in 24% of patients, while 10% discontinued or interrupted atezolizumab during neoadjuvant treatment. Conversely, there were no interruptions for pertuzumab or trastuzumab.
The researchers note that their findings contrast with those of the IMpassion050 trial, which combined neoadjuvant atezolizumab or placebo with dose-dense doxorubicin and cyclophosphamide and found no difference in the pCR rate between the two treatment arms in either the intention-to-treat or PD-L1–positive populations.
They suggest: “The observed discrepancy among efficacy of immunotherapy may be attributed to the difference in antitumor immunity associated with the breast cancer subtype, disease burden, or the partner regimen.”
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