Final Trastuzumab Emtansine Findings Confirm OS Benefit In Advanced HER2-Positive Breast Cancer

EMILIA and TH3RESA trial investigators release the final overall survival results for trastuzumab emtansine in patients previously treated for advanced human epidermal growth factor receptor 2-positive breast cancer

medwireNews: Final results of the EMILIA and TH3RESA trials, published in The Lancet Oncology, confirm the positive impact on overall survival (OS) of the antibody–drug conjugate trastuzumab emtansine for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

“[T]he final overall survival analysis of EMILIA lends further support to the early positioning of trastuzumab emtansine in the therapeutic sequence in patients with HER2-positive metastatic breast cancer, despite the results of TH3RESA showing that trastuzumab emtansine also extends survival when administered as later treatment lines”, writes Filippo Montemurro, from Candiolo Cancer Institute in Torino, Italy, in an accompanying comment.

Nevertheless, he emphasizes: “The more than 900 deaths reported in EMILIA and TH3RESA still remind us that, despite notable median overall survival prolongation, HER2-positive metastatic breast cancer remains a fatal disease in most patients, fully justifying the formidable ongoing research in this field.”

Progression-free survival (PFS) and interim OS data from the EMILIA trial in men or women with HER2-positive unresectable locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane led to approval of trastuzumab emtansine, explain Véronique Diéras, from Institut Curie Paris & Saint Cloud in France, and co-investigators.

The team now reports the final OS to be a median of 29.9 months for the 495 patients randomly assigned to receive trastuzumab emtansine 3.6 mg/kg every 3 weeks versus 25.9 months for the 496 patients given a 21-day cycle of capecitabine 1000 mg/m2 twice daily on days 1–14 and lapatinib 1250 mg/day on days 1–21. This gave a significant hazard ratio (HR) for OS in favour of trastzumab emtansine of 0.75.

“This survival benefit was reported even though 27% of patients had crossed over from capecitabine plus lapatinib to trastuzumab emtansine”, the authors say, adding that the drug–conjugate had a “favourable safety profile” consistent with earlier trial findings.

Ian Krop, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, and co-investigators of the TH3RESA trial report the final OS results for the study, which compared trastuzumab emtansine against a physician’s choice of treatment for patients with HER2-positive advanced breast cancer that had previously been treated with trastuzumab and lapatinib, as well as a taxane at an advanced or earlier stage.

Median OS was significantly longer in the 404 patients randomly assigned to receive trastuzumab emtansine than their 198 counterparts given physician’s choice of systemic, hormone or HER2-directed treatment, at 22.7 versus 15.8 months and a HR of 0.68.

“Thus, trastuzumab emtansine offers patients with previously treated HER2-positive metastatic breast cancer an effective therapeutic option with an acceptable safety profile, without the need for conventional systemic chemotherapy”, Ian Krop et al write.

“Perhaps most importantly, these data show the relevance of HER2 as a therapeutic target even after multiple lines of therapy”, they continue. “This observation has profound implications for drug development in HER2-positive metastatic breast cancer, suggesting that other drugs targeting HER2 might provide patients with additional clinical benefit.”

The EMILIA investigators add: “At present, trastuzumab and pertuzumab plus taxane is the recommended first-line treatment regimen for patients with HER2-positive metastatic breast cancer.

“Additional data are needed on the clinical activity of trastuzumab emtansine in patients previously exposed to both trastuzumab and pertuzumab.”

References

Montemurro F. Trastuzumab emtansine in HER2-positive metastatic breast cancer. Lancet Oncol; Advance online publication 16 May 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30303-0

Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol; Advance online publication 16 May 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30312-1

Krop IE, Kim S-B, Gonzalez Martin A, et al. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol; Advance online publication 16 May 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30313-3

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