Trastuzumab deruxtecan outperforms trastuzumab emtansine

Both trastuzumab deruxtecan and trastuzumab emtansine have shown to improve progression-free survival (PFS) in patients with HER2-positive metastatic breast cancer. In a head-to-head comparison, trastuzumab deruxtecan proved to outperform trastuzumab emtansine.

Trastuzumab deruxtecan is a HER2-targeting, antibody-drug conjugate for the treatment of previously treated patients with advanced HER2-positive metastatic breast cancer, as was demonstrated by the DESTINY-Breast01 study (NCT03248492) [1]. Before, the EMILIA trial (NCT00829166) showed trastuzumab emtansine to be beneficial in this population [2]. In the phase 3 DESTINY-Breast03 (NCT03529110) trial the efficacy and safety of trastuzumab deruxtecan and trastuzumab emtansine are compared head-to-head in patients previously treated with trastuzumab and taxane. The primary analysis demonstrated trastuzumab deruxtecan to have a clinically meaningful and statistically significant improved PFS versus trastuzumab emtansine. Trastuzumab deruxtecan demonstrated superior PFS versus trastuzumab emtansine (HR 0.28; P<0.0001); median PFS was not reached for trastuzumab deruxtecan versus 6.8 months for trastuzumab emtansine; 12-month PFS rate was 79.7% versus 34.2%, respectively [3]. Now, Dr Sara Hurvitz (University of California, CA, USA) presented results from subgroup analyses of DESTINY-Breast03, including patients with brain metastases [4].

Median PFS favoured trastuzumab deruxtecan over trastuzumab emtansine independent of hormone receptor status, prior trastuzumab treatment, and number of prior lines of therapy. For patients with stable brain metastases at baseline (n=82), median PFS was 15.0 months for trastuzumab deruxtecan versus 3.0 months for trastuzumab emtansine (HR 0.25; see Figure). Overall, confirmed overall response rate (ORR) for trastuzumab deruxtecan was 79.7% (16.1% complete response, 63.6% partial response) versus 34.2% (8.2% complete response, 25.5% partial response) for trastuzumab emtansine. In patients with stable brain metastases at baseline, ORR was 67.4% (4.7% complete response, 62.8% partial response) for trastuzumab deruxtecan versus 20.5% (0% complete response, 20.5% partial response) for trastuzumab emtansine. In addition, intracranial response rate in these patients was 63.9% (27.8% complete response, 36.1% partial response) for trastuzumab deruxtecan versus 33.4% (2.8% complete response, 30.6% partial response) for trastuzumab emtansine.

Figure: Progression-free survival of patients with and without brain metastases treated with trastuzumab deruxtecan or trastuzumab emtansine [4].



 

 

 

 

mPFS, median progression-free survival; PFS, progression-free survival.

Overall, the safety profile of trastuzumab deruxtecan was manageable and comparable with its known safety profile. Adjudicated drug-related interstitial lung disease/pneumonitis was reported in 27 (10.5%) patients treated with trastuzumab deruxtecan and 5 (1.9%) patients treated with trastuzumab emtansine, with no grade 4 or 5 events.

“Consistent PFS and ORR benefits with trastuzumab deruxtecan versus trastuzumab emtansine were observed across subgroups in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes, including patients with brain metastases,” concluded Dr Hurvitz.

1. Modi S, al. N Engl J Med 2020;382:610–621.
2. Verma S, Miles D, et al. N Engl J Med 2012; 367:1783-1791.
3. Cortés J, et al. Ann Oncol. 2021;32(suppl5):1283–1346.
4. Hurvitz S, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) vs. trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): subgroup analyses from the randomized phase 3 study DESTINY-Breast03. GS3-01, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022