Q&A With Filippo Montemurro, MD: Considerations for Treatment With Trastuzumab Emtansine
Filippo Montemurro, MD
Recent results from the EMILIA and TH3RESA randomized phase 3 trials (ClinicalTrials.gov Identifiers: NCT00829166, NCT01419197) of trastuzumab emtansine (T-DM1) in patients with previously treated HER2-positive advanced and metastatic breast cancer confirm that the antibody-drug conjugate improves overall survival.1,2
Cancer Therapy Advisor asked Filippo Montemurro, MD, director of investigative clinical oncology at the Candiolo Cancer Institute in Italy, to place these findings in context with respect to when T-DM1 might be best indicated.3 Dr Montemurro authored an editorial in The Lancet Oncology accompanying publication of these 2 studies.
Cancer Therapy Advisor (CTA): With the EMILIA and TH3RESA studies showing the benefits of T-DM1 in patients with HER2-positive metastatic breast cancer regardless of previous therapies, do you believe this treatment will be implemented as a standard therapy? If not, why not?
Dr Montemurro: This treatment is already recommended by several national and international guidelines. The initial publication of these 2 randomized trials led to the approval of T-DM1 in 2 clinical situations involving women with metastatic, HER2-positive breast cancer.
One is represented by patients who experience metastatic progression while on adjuvant trastuzumab or within 6 months of completion of adjuvant trastuzumab. In this case, patients receive T-DM1 as first-line treatment for metastatic disease.
The other situation is patients who have developed resistance to prior anti HER2-treatments for metastatic disease, like trastuzumab, pertuzumab, and lapatinib. Basically, these patients may receive T-DM1 as second or further line of treatment.
CTA: In The Lancet Oncology editorial, you state, “…one practical issue is when best to give trastuzumab emtansine to these patients. Should we use trastuzumab emtansine as early as possible in patients resistant to trastuzumab (and pertuzumab), or is it better used as a salvage treatment after other options have been exhausted?” What would you recommend to clinicians?
Dr Montemurro: Results of the EMILIA and TH3RESA trial show that T-DM1 yields survival benefits compared with alternative choices for any treatment line, early or later in the course of the disease.
Therefore, one may consider saving this treatment as a salvage therapy, when the patient has exhausted other options. Because of the high costs of T-DM1 compared with other second line and beyond options, this therapeutic policy could be considered more affordable from an economic perspective.
Two points must, however, be considered: first, T-DM1 is associated with a more favorable safety profile compared, for example, with lapatinib and capecitabine or with trastuzumab combined with chemotherapy. Second, although there are notable exceptions to this rule (ie, patients with slowly growing disease, with hormone receptor co-expression and who could be managed with endocrine therapy plus anti HER2-therapy), the HER2 abnormality can be associated with very aggressive disease course.
In some of these cases, rapid progression may preclude the administration of further treatments. In this case, one would regret not having used a drug that prolongs overall survival earlier, when the patients' conditions were more favorable and the treatment feasible.