Does T-DM1 have a different impact on symptoms in breast cancer compared to alternative treatment?

This study evaluated the benefit of the new HER2-targeted therapy T-DM1 compared to an often-used alternative treatment.

Breast cancers expressing the human epidermal growth factor receptor 2 protein are known as HER2-positive cancer. In recent years therapies that directly target the HER2 protein, for example trastuzumab (Herceptin), have been developed leading to increased patient response and survival.

Trastuzumab emtansine (T-DM1) is another such drug; it works in a similar way to trastuzumab by killing cells that have high levels of HER2. Previous studies have shown this drug to be associated with significantly longer time before disease progression and overall survival compared to a combination of capecitabine (Xeloda) and lapatinib (Tyverb). However, it is important to make sure that such improvements do not come at the cost of worsened patient symptoms.

This paper investigated the benefit of T-DM1 compared with capecitabine and lapatinib on symptoms of patients with local and metastatic cancer (cancer that has spread to distant organs).

991 patients who were previously treated with a taxane–chemotherapy (paclitaxel [Taxol] or docetaxel [Taxotere]) and trastuzumab were chosen as part of this study. They were randomly divided into two groups; one group received T-DM1 (495) while the other received capecitabine and lapatinib (496). All patients had HER2 positive cancer that was either local (has not spread to distant organs) but not suitable for surgery, or metastatic.

Patients took two questionnaires to establish the status of their symptoms. One questionnaire evaluated information on physical and functional wellbeing. Scores ranged from 0-92 with higher scores indicating a better quality-of-life. A second questionnaire was used to investigate the frequency, urgency, consistency and discomfort of diarrhea experienced by a patient. Questionnaires were completed at weeks 12, 24, 36, to compare the two treatments.

At the time of final follow-up (48 weeks) significant improvement in symptoms was observed in both the T-DM1 (55.3%) and capecitabine and lapatinib (49.4%) groups.

Over the course of the study, the number of people reporting diarrhea symptoms in the capecitabine and lapatinib group increased by 1.5- to 2-fold. The T-DM1 group reported no significant change in diarrhea status.

Average time to worsening of symptoms was significantly longer in the T-DMI group (6.0 months) compared to the capecitabine and lapatinib group (4.3 months).

The study concluded that T-DM1 has a significant ability to delay worsening of symptoms for patients with HER2-positive cancer when compared to established alternative treatment.

Filling out of the questionnaire decreased throughout the investigation, therefore patient satisfaction and outcome may be altered by more complete patient reporting.