T-DM1 EFFICACY

SAN ANOTONIO — Final clinical trial results for T-DM1, or ado-trastuzumab (Kadcyla, Roche/Genentech), "further solidify" the role of the drug in the treatment of advanced HER2-positive breast cancer patients who have undergone previous treatment with other drugs, including trastuzumab (Herceptin, Roche/Genentech) and chemotherapy, said an investigator here at the San Antonio Breast Cancer Symposium 2015.

The data come from TH3RESA, a phase 3 clinical trial of heavily pretreated patients with advanced disease who had received at least two previous therapies – and about two-thirds had four or more — before T-DM1. Most of those treatments (about 80%) consisted of trastuzumab-containing regimens.

Only a handful of patients had locally advanced disease; about 95% had metastatic disease. Median follow-up was 30.5 months.

Median overall survival was better in the 404 patients who received T-DM1 than in the 198 who received "physician's choice" of treatment (22.7 vs 15.8 months). And there was a 32% reduction in the risk for death with T-DM1 (hazard ratio, 0.68; 95% confidence interval, 0.54 - 0.85; P = .0007).

The results are clinically meaningful and highly statistically significant, said lead author Hans Wildiers, MD, PhD, a medical oncologist at KU Leuven in Belgium.

The benefit was seen despite the fact that about half the patients in the T-DM1 group crossed over once favorable results from another trial were made public. That trial, known as EMILIA, formed the basis of approval for the product.

After more than 3 years, 25% of the T-DM1-treated patients are still on the study drug, Dr Wildiers reported.

The duration of treatment with either trastuzumab or T-DM1 is indefinite, as long as disease is stable. Thus, patients who have long-term success are now prompting clinicians to question whether the drugs can be stopped at some point, said C. Kent Osborne, MD, from the Baylor College of Medicine in Houston, who is one of the meeting directors.

The new study serves as a reminder of how much has changed in the treatment — and perception — of HER2-positive breast cancer, said Dr Osborne. In the past, "we hated to see a patient come in with a HER2-positive tumor," he explained. But now these are considered to be relatively "good" tumors because of advances in treatment. There are now four HER2-specific drugs on the market.

The incidence of adverse events of grade 3 or higher was lower in the T-DM1 group than in the physician's-choice group (40.0% vs 47.3%). And about half as many patients in the T-DM1 group as in the physician's-choice group withdrew from the trial (8.2% vs 15.7%).

Dr Wildiers noted that there were no quality-of-life data in the study.

But Dr Osborne pointed out that you can estimate quality of life using adverse events. Overall, T-DM1 had "far fewer" adverse effects than physician's choice, which included chemotherapies and lapatinib, he summarized.

In meeting press materials, it was noted that National Comprehensive Cancer Network guidelines on the treatment of HER2-positive breast cancer recently began to recommend T-DM1 as a preferred treatment for patients whose metastatic disease has progressed after treatment with a combination of a taxane-based chemotherapy and trastuzumab, with or without pertuzumab (Perjeta, Roche).

T-DM1 appears to be best suited as a later line of treatment in advanced disease. Notably, T-DM1 was no more effective than trastuzumab in slowing disease progression in the randomized MARIANNE trial of 1095 treatment-naïve patients with locally advanced or metastatic disease.

This study was supported by Roche. Dr Wildiers reports that his institution has received compensation from Roche for lectures he has presented at national meetings and for consulting work, as well as an unrestricted research grant for academic research.

San Antonio Breast Cancer Symposium (SABCS) 2015: Abstract S5-05. Presented December 11, 2015.