Trastuzumab deruxtecan also effective in patients with brain metastases

Trastuzumab deruxtecan (T-DXd) exhibited substantial and durable overall and intracranial clinical activity in a large cohort of patients with metastatic HER2+ breast cancer, irrespective of the presence of brain metastases in the phase 3b/4 DESTINY-Breast12 trial.

Approximately half of the patients with metastatic HER2+ breast cancer will develop brain metastases during the course of their disease. Historically, the prognosis for patients with brain metastases has been poor [1]. However, in the case of HER2+ breast cancer, more patients are experiencing longer survival as systemic treatments for extracranial disease, such as T-DXd, continue to improve.

So far, intracranial activity of T-DXd has been observed in small or retrospective patient cohorts with HER2+ metastatic breast cancer with stable or active brain metastases. The phase 3b/4 DESTINY-Breast12 trial (NCT04739761) was designed to assess the efficacy and safety of T-DXd in patients with HER2+ breast cancer with or without brain metastases, and whose disease had progressed on prior anti-HER2-based regimens [2].

DESTINY-Breast12 enrolled 504 participants, of whom 263 had brain metastases at the time of enrolment. The primary endpoint in the cohort with brain metastases was progression-free survival (PFS); the primary endpoint in the cohort without brain metastases was overall objective response (ORR). Dr Nancy Lin (Dana-Farber Cancer Institute, MA, USA) presented the primary results.

Median PFS in participants with brain metastases was 17.3 months; the 12-month PFS rate was 61.6%. No significant differences were observed between participants with stable versus active brain metastases. The CNS PFS rate at 12 months was 58.9% and the intracranial response rate was 71.7%; also with no significant difference between patients with stable or active brain metastases. ORR in participants without brain metastases was 62.7%. The additional endpoint of 12-month overall survival rate was 90.3% and 90.6% in the cohort with or without brain metastases, respectively.

While no new safety signals were observed, toxicity remains an issue, with 9 patients (3.5%) experiencing grade 5 ILD/pneumonitis. Mortality rate was highest in the cohort with brain metastases (6 cases, co-occurring with opportunistic infection in 4 cases). It should be noted that this high mortality is observed in experienced cancer centres and it is reasonable to expect that the mortality rate is higher in community hospitals. More analyses are needed to fully understand the reason for death and the role of opportunistic infection. In the meantime, all patients who develop ILD (and who in general have some lymphopenia) and start steroids, as well as those who receive steroids for another reason, require prophylactic treatment for the prevention of opportunistic infections.

“These results support the use of T-DXd for patients with HER2+ breast cancer, irrespective of the presence of brain metastases,” concluded Dr Lin.

1. Ramakrishna N, et al. J Clin Oncol 2022;40:2636-2655.
2. Lin NU, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2⁺ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results. Abstract LBA18, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024