OS benefit of adjuvant T-DM1 in early breast cancer with residual disease after neoadjuvant therapy

In patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy, adjuvant treatment with trastuzumab emtansine (T-DM1) improves both invasive disease-free survival (IDFS) and overall survival (OS), according to updated results of the phase 3 KATHERINE trial.

Patients with HER2-positive early breast cancer who have residual disease after receiving neoadjuvant chemotherapy plus HER2-targeted therapy have a worse prognosis than those who have no residual disease [1]. Interim results from the phase 3 KATHERINE trial (NCT01772472) demonstrated a higher 3-year IDFS rate in these patients after adjuvant treatment with 14 cycles of T-DM1 versus 14 cycles of trastuzumab. OS was not significantly different between both arms at the time of this interim analysis [2]. Prof. Sibylle Loibl (Goethe University, Germany) presented results from the final IDFS and an updated OS analysis [3].

In KATHERINE, 1,386 patients with HER2-positive early breast cancer who had residual disease after receiving neoadjuvant chemotherapy plus HER2-targeted therapy with trastuzumab were 1:1 randomised to receive 14 cycles of T-DM1 or 14 cycles of trastuzumab within 12 weeks after surgery. The primary endpoint was IDFS, key secondary endpoints were OS and distant recurrence-free survival (DRFS).

With a median follow-up of 8.4 years, T-DM1 sustained the improvement in IDFS over trastuzumab; 7-year IDFS rates were increased from 67.1% with trastuzumab to 80.8% with T-DM1 (HR 0.54; 95% CI 0.44–0.66]; P<0.0001). In addition, 7-year OS rates were significantly increased from 84.4% with trastuzumab to 89.1% with T-DM1 (HR 0.66; 95% CI 0.51–0.81; P=0.0027). Both IDFS and OS benefit was observed across all prespecified subgroups.

No new safety issues emerged with longer follow-up and cardiac toxicity was rare in both arms (0.7%).

Based on these results, Prof. Loibl concluded that “KATHERINE demonstrates a significant improved OS and sustained IDFS in patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy who are treated with T-DM1 versus trastuzumab post-surgery.” Follow-up is ongoing for the final OS analysis.

1. Cortazar P, et al. Lancet 2014;384:164-172.
2. von Minckwitz G, et al. N Engl J Med 2019;380:617-628.
3. Loibl S, et al. Phase III study of adjuvant ado-trastuzumab emtansine vs trastuzumab for residual invasive HER2-positive early breast cancer after neoadjuvant chemotherapy and HER2-targeted therapy: KATHERINE final IDFS and updated OS analysis. Abstract GS03-12, SABCS 2023, 5–9 December, San Antonio, TX, USA.

 

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Posted on 11 January 202411 January 2024