Ado-trastuzumab emtansine extends DFS in early-stage HER2-positive breast cancer
SAN ANTONIO — Ado-trastuzumab emtansine extended DFS compared with paclitaxel plus trastuzumab among patients with early-stage HER2-positive breast cancer, according to results of the randomized phase 2 ATEMPT trial presented at San Antonio Breast Cancer Symposium.
However, ado-trastuzumab emtansine (Kadcyla, Genentech) was not associated with fewer clinically relevant toxicities compared with paclitaxel plus trastuzumab (Herceptin, Genentech).
“We knew that patients with early-stage HER2-positive breast cancer are at more than an insignificant risk for recurrence, with retrospective series of untreated patients suggesting rates for recurrence between 10% and 30%,” Sara M. Tolaney, MD, MPH, breast medical oncologist at Dana-Farber Cancer Institute and a HemOnc Today Next Gen Innovator, told Healio. “We previously conducted ... the APT trial, which demonstrated that paclitaxel plus trastuzumab was associated with a 7-year DFS rate of 93%, with only four distant recurrences.
“We were interested in developing a less toxic treatment regimen that would be highly effective and knew that [ado-trastuzumab emtansine] was associated with excellent efficacy in metastatic HER2-positive disease and associated with less toxicity compared with chemotherapy plus trastuzumab,” Tolaney added. “Therefore, [ado-trastuzumab emtansine] seemed like a reasonable approach.”
Researchers conducted the ATEMPT trial to examine whether ado-trastuzumab emtansine was associated with a clinically acceptable event rate compared with paclitaxel plus trastuzumab.
The trial enrolled 512 patients with early-stage HER2-positive breast cancer, and 497 began protocol therapy. The majority (73%) had hormone receptor-positive tumors (T1a, 11%; T1b, 31%; T1c, 57%).
Researchers randomly assigned patients 383 patients (median age, 56 years) to 3.6 mg/kg ado-trastuzumab emtansine via IV every 3 weeks for 17 cycles. The other 114 patients (median age, 55 years) received 80 mg/m2 IV paclitaxel plus 2 mg/kg IV trastuzumab weekly for 12 cycles, followed by 6 mg/kg trastuzumab every 3 weeks for 13 cycles.
Researchers allowed for adjuvant radiation and endocrine therapy to be initiated after completion of 12 weeks of study treatment.
DFS at 3-years in the ado-trastuzumab group, as well as a comparison of clinically relevant toxicities, served as co-primary endpoints. Median follow-up was 3.1 years.
Results showed 3-year DFS was 97.7% (95% CI, 96.2-99.3) among patients assigned ado-trastuzumab emtansine and 92.8% (95% CI, 87.8-98.1) among those assigned paclitaxel plus trastuzumab.
Researchers observed 10 DFS events in the ado-trastuzumab group. Two patients experienced local or regional recurrences, three patients developed new contralateral primary breast cancers and two patients developed distant recurrences. Three patients died of causes not associated with breast cancer.
Seven DFS events, including two distant recurrences, occurred in the paclitaxel-trastuzumab group.
The recurrence free interval — defined as invasive local or regional recurrences, distant recurrences and any breast cancer-associated death — was 99.1% with ado-trastuzumab emtansine.
Forty-six percent of patients in each treatment group developed clinically relevant toxicities. Researchers observed a higher rate of grade 2 or higher neurotoxicity in the paclitaxel-trastuzumab group (23% vs. 11%).
A comparable percentage of patients assigned ado-trastuzumab emtansine and paclitaxel-trastuzumab experienced grade 3 or higher nonhematologic toxicity (10% vs. 11%) and grade 4 or higher hematologic toxicity (1% vs. 0%)
A similar number of patients required dose delays due to any toxicity (28% vs. 26%). However, more patients assigned ado-trastuzumab emtansine discontinued treatment early due to any toxicity (17% vs. 6%).
“There were differences in the toxicity profiles between the two arms, with paclitaxel plus trastuzumab having more neuropathy [24% vs. 11%], neutropenia [13% vs. 3%] and infusion-related reactions [11% vs. 5%], and [ado-trastuzumab emtansine] having more thrombocytopenia [11% vs. 1%] and elevated liver function [9% vs. 4%],” Tolaney told Healio. “Given the low event rate observed with [ado-trastuzumab emtansine] in the study, [the agent] can be considered an alternative treatment for select patients with early-stage HER2-positive disease who are concerned about paclitaxel plus trastuzumab-associated toxicities.” – by Jennifer Southall
Tolaney SM, et al. Abstract GS1-05. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2019; San Antonio.
Disclosures: Tolaney reports institutional research support from AstraZeneca, Bristol-Myers Squibb, Cyclacel Pharmaceuticals, Eisai, Eli Lilly, Exelixis, Genentech, Immunomedics, Merck, Nektar, Novartis, Odenate, Pfizer and Sanofi; and consultant/advisory roles with AbbVie, AstraZeneca, Athenex, Bristol-Meyers Squibb, Celldex, Daiichi-Sankyo, Eisai, Eli Lilly, Genentech, Immunomedics, Merck, Nanostring Technologies, Nektar, Novartis, Paxman, Pfizer, Puma Biotechnology, Sanofi and Seattle Genetics. Please see the abstract for all other authors’ relevant financial disclosures.