Trastuzumab deruxtecan triples PFS

At a prespecified interim analysis of DESTINY-Breast03, comparing trastuzumab deruxtecan (T-DXd) head-to-head with trastuzumab emtansine (T-DM1), T-DXd reduced the risk of disease progression or death by 72% compared with T-DM1. This was presented in the first Presidential Symposium.

The global head-to-head, open-label, randomised, phase 3 DESTINY-Breast03 study (NCT03529110) interim analysis was presented by Dr Javier Cortés (International Breast Cancer Center Barcelona, Spain) [1]. DESTINY-Breast03 evaluated the safety and efficacy of T-DXd (n=261; 5.4 mg/kg) versus T-DM1 (n=263; 3.6 mg/kg) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane, primarily as their first-line treatment. The primary endpoint of DESTINY-Breast03 was progression-free survival (PFS) based on blinded independent central review. Secondary efficacy endpoints included overall survival (OS), PFS based on investigator assessment, objective response rate, duration of response, clinical benefit rate, and safety.

After 15.5 and 13.9 months of follow-up in the T-DXd and T-DM1 arms respectively, blinded independent central review determined that the median PFS for patients treated with T-DXd was not reached compared with 6.8 months for T-DM1 (HR 0.28; P<0.0001; see Figure). The key secondary endpoint of PFS assessed by investigators showed that patients treated with T-DXd experienced a 3-fold improvement in PFS of 25.1 months versus 7.2 months with T-DM1 (HR 0.26; P<0.0001). PFS benefit was consistent across key subgroups of patients treated with T-DXd, including those with a history of stable brain metastases. Differences in estimated 12-month OS (94.1% with T-DXd vs 85.9% with T-DM1) did not cross the pre-specified boundary for significance (HR 0.56; 95% CI 0.36–0.86) but showed a strong interim trend, and will be followed up as the data mature.

Figure: PFS determined by blinded independent central review, the primary endpoint of DESTINY-Breast03 [1]



The safety profile of the most common adverse events with T-DXd in DESTINY-Breast03 was consistent with previous data, and no new safety concerns were reported. Interstitial lung disease was reported in 10% of the patients in the T-DXd arm, versus 2% in the T-DM1 arm, yet these numbers are lower than described in earlier trials with T-DXd.

The designated discussant, Dr Shanu Modi (Memorial Sloan-Kettering Cancer Center, New York, USA) declared, “The efficacy seen in this trial is unprecedented.”

1. Cortés J, et al. Trastuzumab Deruxtecan (T-DXd) vs Trastuzumab Emtansine (T-DM1) in Patients (Pts) With HER2+ Metastatic Breast Cancer (mBC): Results of the Randomized Phase 3 DESTINY-Breast03 Study. Abstract LBA1, ESMO Congress 2021, 16–21 September.

Want to read more? Medicom has a featured interview with Prof. Cortés about the DESTINY-Breast03 trial: Second-line trastuzumab deruxtecan for metastatic HER2-positive breast cancer.

 

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Posted on 19 November, 202129 February, 2024