That HERt.

Top Line: Do women with HER2+ early stage breast cancer benefit from neoadjuvant immunotherapy?

The Study: Thus far, KEYNOTE-522 has shown that the addition of pembrolizumab to neoadjuvant chemotherapy (as well as maintenance pembro) for stage II and III triple negative breast cancer (TNBC) increases pathologic complete response rate from 51→ 65% and 3-year event free survival (EFS) from 77→ 85%. IMpassion050 was designed to test the same concept in 454 patients with HER2+ breast cancer, a >2cm primary tumor, and positive lymph nodes. Standard therapy consisted of neoadjuvant doxorubicin plus cyclophosphamide followed by neoadjuvant paclitaxel plus pertuzumab and trastuzumab, and then 1 year of maintenance pertuzumab and trastuzumab. Patients were randomized to the addition of atezolizumab in both the neoadjuvant and maintenance phases. The study was designed to detect an 18% improvement in the pCR rate (65→ 83%). Unfortunately, the addition of atezolizumab did not budge the pCR rate (62.4% v 62.7%). In addition, there was no significant improvement in pCR even in the PD-L1+ cohort (72.5% v 64.2%). Toxicity was significantly higher in the atezolizumab arm with 5 grade 5 events all in the atezo arm. The authors hope there is still more to come on the event-free survival front as patients in KEYNOTE-522 who didn’t have a pCR seemed to derive a greater EFS benefit from immunotherapy.

TBL: The addition of atezolizumab to neoadjuvant chemotherapy and HER2 targeted therapy does not increase the pathologic complete response rate for HER2+ breast cancer. | Huober, J Clin Oncol 2022