Patients With HER2+ Breast Cancer Who Achieve pCR With Neoadjuvant HER2-Targeted Therapy Have Better DFS, OS

Joyce O’Shaughnessy, MD

Patients with HER2-positive, early-stage breast cancer who achieved a pathologic complete response (pCR) after receiving HER2-targeted therapy experienced better outcomes in terms of disease-free survival (DFS) and overall survival (OS) vs those who did not, according to data from a real-world study.¹

Results, which were presented during the 2021 San Antonio Breast Cancer Symposium, showed that at a median follow-up of 33 months, the median OS from neoadjuvant treatment initiation had not yet been reached among the 614 patients included. The estimated survival rate at 3 years was 97.0% (95% CI, 94.9%-98.3%). Notably, the estimated 3-year survival rate was lower in those who did not achieve a pCR with treatment (n = 429) vs those who did (n = 185), at 96.0% (95% CI, 92.8%-97.8%) and 98.8% (95% CI, 95.2%-99.7%), respectively. The 3-year DFS rate was also lower in those without a pCR, at 87.5% and 92.2%, respectively.

Fifteen patients with a pCR experienced disease recurrence vs 44 without a pCR; recurrence rates in these groups were 8.1% (95% CI, 4.6%-13.0%) and 10.3% (95% CI, 7.6%-13.5%), respectively. The overall 3-year recurrence rate was 9.6% (95% CI, 7.4%-12.2%). Additionally, the median time to recurrence was 21.1 months (range, 0.03-60.3) in those with a pCR vs 18.6 months (range, 0.03-42.4) in those without. The overall median time to recurrence was 18.8 months (range, 0.03-60.3).

“Patients with non-pCR had a risk recurrence of 10.3% over approximately a 3-year time period,” Joyce O’Shaughnessy, MD, chair of Breast Cancer Research and the Celebrating Women Chair in Breast Cancer at Baylor-Sammons Cancer Center, chair and member of the Scientific Advisory Board of the The US Oncology Network, and 2016 Giants of Cancer Care award winner, and colleagues, wrote in the poster on the data. “During our study period, which ran from 2014 to 2021, 28.0% of non-pCR patients received ado-trastuzumab emtansine [Kadcyla; T-DM1] as adjuvant treatment.”

Approximately 15% to 25% of breast cancers have HER2 overexpression and/or amplification, and this is known to be a risk factor that is linked with poor clinical outcomes. The National Comprehensive Cancer Network guidelines currently recommend the use of chemotherapy and HER2-based therapy in the neoadjuvant setting for patients with HER2-positive early-stage breast cancer who are candidates for surgery.

HER2-targeted therapies have been shown to be beneficial in terms of recurrence and survival rates in this population, but the outcomes of those treated in a community practice setting who have achieved a pCR to neoadjuvant therapy or who had residual disease at the time of definitive surgery have not been well characterized.

With the preliminary evaluation of the real-world study, investigators sought to describe the patient characteristics, DFS, and OS in those with and without a pCR after neoadjuvant HER2-targeted treatment in the community setting.

The study comprised a retrospective, observational cohort of adult patients who were diagnosed with stage I, II, or III HER2-positive breast cancer, received neoadjuvant HER2-targeted therapy between April 1, 2014 and March 31, 2019, and had a confirmed pCR status. Patients who enrolled in clinical trials at any point during the study period or received treatment for another documented primary cancer diagnosis were excluded from the analysis.

Investigators collected data from The US Oncology Network’s electronic healthcare record database, and natural language processing/artificial intelligence was leveraged to identify those with a pCR status and those with disease recurrence during the study period.

Investigators descriptively evaluated patient and disease characteristics, risk of refcurrence, and time to recurrence. Moreover, recurrence was detected by evidence of recurrence or metastases described in healthcare records, and Kaplan-Meier methods were utilized to evaluate OS and DFS from the start of neoadjuvant therapy, with results stratified by pCR status.

Among the overall cohort of 614 patients, 30% had confirmed pCR and 70% had non-pCR. The overall median age of these patients at diagnosis was 55 years (range, 23-88), 99.3% were female, 79.0% were White, and 76.0% had an ECOG performance status ranging from 0 to 1. At the time of diagnosis, 78% of patients had stage I or II disease, and 21% had stage III disease. Moreover, 52.3% of patients had positive hormone receptor status.

“There are limitations to identifying recurrences in electronic data, including under ascertainment of recurrence,” the study authors concluded. “The residual risk of recurrence among non-pCR patients suggests a potential opportunity to improve long-term outcomes with additional therapies in this group.”

Reference

1. O’Shaughnessy J, Oestreicher N, Fulcher N, et al. Outcomes of patients with pathologic complete response following neoadjuvant HER2-tareted therapy in patients with HER2+ early-stage breast cancer. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021. San Antonio, TX. Abstract P3-12-20.