Trastuzumab deruxtecan offers long-term survival benefits in HER2+ metastatic breast cancer

HER2-positive metastatic breast cancer (mBC) patients who had been treated with trastuzumab emtansine continue to enjoy survival benefits with trastuzumab deruxtecan (TD) relative to those who received treatment of physician’s choice (TPC), as shown by the updated results of the DESTINY-Breast (DB)-02 study. TD also boasts of a manageable safety profile, with no long-term toxicity.

“With longer follow-up, results reinforce the substantial benefit of TD over TPC in patients with HER2-positive mBC previously treated with trastuzumab emtansine, demonstrated by clinically meaningful improvement in efficacy over TPC,” said lead author Dr Sung-Bae Kim from the Asan Medican Center, University of Ulsan College of Medicine in Seoul, Korea.

DB-02 is a randomized, open-label, phase III trial comparing the efficacy and safety of TD with TPC in patients previously managed with trastuzumab emtansine for HER2-positive mBC. The primary analysis revealed significant improvement in progression-free survival (PFS) and overall survival (OS) with TD compared with TPC. [Lancet 2023;401:1773-1785]

“Here we report updated efficacy and safety results of the DB-02 study with longer follow-up (median 26.8 months),” Kim said.

Kim and colleagues randomly assigned 608 patients in a 2:1 ratio to receive TD (n=406) or TPC (n=202; trastuzumab plus capecitabine or lapatinib plus capecitabine). They then estimated the OS, PFS, PFS from time of randomization to the progression on next line of therapy or death (PFS2), and safety.

The median follow-up at data cutoff (29 September 2023) was 30.2 months with TD and 20.5 months with TPC. The median treatment duration was 11.3 months with TD and approximately 4.5 months with TPC. [ESMO Breast Cancer 2024, abstract 192MO]

Survival

OS was significantly longer in the TD arm (median, 35.7 months, 95 percent confidence interval [CI], 30.9‒40.8) than in the TPC arm (median, 25.0 months, 95 percent CI, 20.4‒31.5), as was PFS2 (median, 33.0 vs 15.0 months, respectively).

In addition, the OS rates at 24 months were 64.6 percent (95 percent CI, 59.6‒69.2) with TD and 51.9 percent (95 percent CI, 44.4‒58.9) with TPC. At 36 months, the OS rates were 49.2 percent (95 percent CI, 44.0‒54.3) and 36.6 percent (95 percent CI, 29.5‒43.8), respectively.

Of note, TD was used as a poststudy anticancer treatment by 32 of 248 patients (12.9 percent) in the TD arm and by 69 of 148 (46.6 percent) in the TPC arm.

In terms of safety, the most common treatment-emergent adverse events (TEAEs) with TD were nausea (72.5 percent), fatigue (62.4 percent), and vomiting (38.1 percent), while those with TPC were diarrhoea (53.8 percent), palmar-plantar erythrodysesthesia syndrome (51.3 percent), and nausea (37.4 percent).

TEAEs leading to treatment discontinuation occurred in nearly one in five (21.5 percent) TD-treated patients and one in 10 (9.7 percent) TPC-treated patients. Overall, 86.4 percent of patients in the TD arm and 100 percent in the TPC arm ceased treatment, with progressive disease (47.8 percent vs 73.8 percent) as the main reason, followed by AEs (20.3 percent vs 7.2 percent) and withdrawal by patient (9.2 percent vs 8.7 percent).

Additionally, 46 (11.4 percent) cases of adjudicated drug-related interstitial lung disease/pneumonitis were recorded in the TD arm.

“These data confirm the long-term survival benefit, as well as favourable benefit/risk profile of TD in patients with HER2-positive mBC who have been previously treated with trastuzumab emtansine,” Kim said.