Positive Survival Outcomes With/ Without Paclitaxel in Patients With HER2+ Breast Cancer

Promising survival rates were shown in patients with different subtypes of early breast cancer who had a pathological complete response (CR) after de-escalated 12-week trastuzumab (Herceptin) plus pertuzumab (Perjeta) with or without weekly paclitaxel, according to 5-year survival data from the WSG-ADAPT-HER2+/HR– trial (NCT01817452).

Findings revealed that excluding further chemotherapy did not affect invasive disease-free survival (iDFS) within patients with a pathological CR. Additionally, the use of weekly paclitaxel plus dual HER2 blockade for 12 weeks is a potentially efficacious de-escalated neoadjuvant regimen when used in patients with hormone receptor-negative, HER2-positive early breast cancer with high pathological CR rates and good 5-year outcomes, according to results published in the Lancet Oncology.

The prospective, randomized, multicenter, open-label, phase 2 trial is a part of the ADAPT umbrella trial examining patients with different subtypes of early breast cancer. The 5-year analysis of the trial aimed to evaluate survival data as well as the effect of pathological CR, early therapy response, and molecular subtype of patients.

Enrollment was open to female patients aged 18 years or older with histologically confirmed, unilateral, primary invasive carcinoma of the breast. Other requirements included the breast cancer to be non-inflammatory, patients to have hormone receptor-negative and HER2-positive status and obtain either an ECOG performance status of 0 or 1 or a Karnofsky performance status of at least 80%.

Patients were randomly assigned 5:2 to receive either trastuzumab at an 8 mg/kg loading dose for 12 weeks, then 6 mg/kg every 3 weeks plus pertuzumab at 840 mg loading dose, then 420 mg every 3 weeks, or trastuzumab plus pertuzumab plus paclitaxel at 80 mg/m2 weekly. Both cohorts received the drugs intravenously.

The primary end point of the trial was comparing the number of patients with a pathological CR at surgery of the early responders within the trastuzumab plus pertuzumab group vs all patients in the trastuzumab plus pertuzumab plus paclitaxel group.

Additionally, the primary objective of the ADAPT trial as a whole was to evaluate the effect of pathological CR on iDFS. Secondary end points were 5-year iDFS, relapse-free survival, locoregional relapse-free survival, distant DFS (DDFS), and overall survival.

A total of 134 patients were randomly assigned to treatment, 92 to trastuzumab plus pertuzumab and 42 to trastuzumab plus pertuzumab plus paclitaxel, between March 3, 2014, and Oct 6, 2015. The median follow-up seen in survivors was 59.9 months (Interquartile range, 53.4-61.4).

No significant differences in iDFS, relapse-free survival, locoregional relapse-free survival, DDFS, and overall survival were reported between the treatment groups.

The trastuzumab plus pertuzumab plus paclitaxel group found the proportion of patients achieving 5-year survival to be 98% (95% CI, 84-100) compared to the trastuzumab plus pertuzumab group which was 87% (CI, 78-93) for iDFS (HR, 0.32; 95% CI, 0.07-1.49; P = 0.15).

Other findings revealed there to be 98% (95% CI, 84–100) relapse-free survival vs 89% (HR, 0.41; 95% CI, 0.09–1.91; p = 0·25); 100% (95% CI not estimable) and 95% for locoregional relapse-free survival (HR, 0.41; 95% CI, 0.05-3.75; P = 0·43); 98% (95% CI, 84-100) and 92% for DDFS (HR, 0.35; 95% CI, 0.04-3.12; P = 0·36), and 98% (95% CI, 84-100) and 94% for overall survival (HR, 0.41; 95% CI, 0.05-3.63; P = 0·43).

Further, pathological CR was associated with improved iDFS (HR, 0.14; 95% CI, 0.03-0·64; P = 0.011). There were also 2 iDFS events, 1 in each arm, which happened following the pathological CR.

References:

Nitz U, Gluz O, Graeser M et al. De-escalated neoadjuvant pertuzumab plus trastuzumab therapy with or without weekly paclitaxel in HER2-positive, hormone receptor-negative, early breast cancer (WSG-ADAPT-HER2+/HR–): survival outcomes from a multicentre, open-label, randomized, phase 2 trial. Lancet Oncol. 2022;23(5):p625-635. doi:10.1016/S1470-2045(22)00159-0

A prospective, randomized multicenter, open-label comparison of preoperative combination of trastuzumab and pertuzumab with or without concurrent taxane chemotherapy given for twelve weeks in patients with operable HER2+/HR- breast cancer within the ADAPT protocol (ADAPT). ClinicalTrials.gov. Accessed May 3, 2022. https://bit.ly/3FeEP6p