T-DXd Shows Early OS Benefit in HER2+/HER2-Low Breast Cancer and Leptomeningeal Carcinomatosis

News
Article

The DEBBRAH trial met its primary endpoint of overall survival in a cohort of patients with HER2-positive or HER2-low advanced breast cancer and leptomeningeal carcinomatosis with positive cerebrospinal fluid cytology.

“Despite the limited sample size, T-DXd showed promising activity with no new safety concerns in HER2-positive and HER2-low patients with previously untreated, pathologically confirmed leptomeningeal carcinomatosis,” according to Marta Vaz Batista, MD.

“Despite the limited sample size, T-DXd showed promising activity with no new safety concerns in HER2-positive and HER2-low patients with previously untreated, pathologically confirmed leptomeningeal carcinomatosis,” according to Marta Vaz Batista, MD.

Fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) showed promising activity with no new safety concerns in patients with HER2-positive and HER2-low advanced breast cancer and previously untreated/pathologically confirmed leptomeningeal carcinomatosis, according to findings from a small study of the DEBBRAH study (NCT04420598) presented at the2023 San Antonio Breast Cancer Symposium (SABCS).1

Results of the 7-patient study showed that the median OS with trastuzumab deruxtecan was 13.3 months (95% CI, 5.7-not applicable; P <.001). The 16-week OS rate was 86% (95% CI, 33%-98%), and the 24-week OS rate was 71% (95% CI, 26%-92%).

“Despite the limited sample size, T-DXd showed promising activity with no new safety concerns in HER2-positive and HER2-low patients with previously untreated, pathologically confirmed leptomeningeal carcinomatosis,” lead study author Marta Vaz Batista, MD, a medical oncologist of Hospital Professor Doutor Fernando Fonseca EPE in Lisbon, Portgual, and coinvestigators wrote in the poster that was presented during the meeting.

In this single-arm, open-label, 5-cohort, phase 2 study conducted across 18 sites in Spain and Portugal, 39 patients over the age of 18 years received 5.4 mg/kg of T-DXd intravenously once every 21 days until disease progression, unacceptable toxicity, or consent withdrawal.2 Patients with pretreated HER2-positive or HER2-low advanced breast cancer with stable, progressing, or untreated brain metastases and/or leptomeningeal carcinomatosis were divided into 5 cohorts.

Cohort 5 consisted of 7 patients with HER2-positive or HER2-low advanced breast cancer and leptomeningeal carcinomatosis with positive cerebrospinal fluid cytology. The median age of the cohort was 57 years (range, 42-69). Six patients had less than 3 metastatic organ sites. Three patients had HER2-positive status vs 4 who were HER2 low. The median time before the last prior therapy was 1.9 months (range, 0.7-15). All 7 patients in the cohort had received systematic treatment through chemotherapy, 3 through anti–HER2 therapy, and 3 through endocrine therapy.

Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, time to response, duration of response, and best percentage of change in tumor burden, as per RANO-BM (intracranial lesions) and RECIST v.1.1 (extracranial and overall lesions). Median PFS was 8.9 months (2.1-NR); the 16-week PFS rate was 86% (95% CI, 33%-98%), and the 24-week PFS rate was 71% (95% CI, 26%-92%).

At data cutoff if April 4, 2023, the median follow-up was 12 months (range, 2.5-18.6). The median duration of treatment was 9.0 months (range, 2.1-18.6). Two patients, 1 with HER2-positive and 1 with HER2-low disease, remained on treatment, after 18.6 months and 12.0 months, respectively.

Five patients had disease progression. No patients had intracranial progression, while 4 patients presented extracranial progression. One patient had clinical worsening. No objective responses were observed. Five patients had a prolonged stabilization of at least 24 weeks, resulting in an overall clinical benefit rate of 71.4% (95% CI, 29.0%-96.3%).

All 7 patients experienced any-grade treatment emergent adverse effects (TEAEs), and 3 experienced a grade 3 TEAE. The most common non–hematological TEAEs included nausea (any-grade, 57.1%; grade 3, 14.3%), fatigue (any-grade, 42.9%), vomiting (any-grade, 42.9%), headache (any-grade, 42.9%), and urinary tract infection (any-grade, 42.9%).

In terms of hematological TEAEs, anemia (any-grade, 42.9%) and thrombocytopenia (any-grade, 28.6%; grade 3, 14.3%) were the most frequent. Four patients experienced serious unrelated TEAEs, and 1 patient experienced a treatment-related serious TEAE of grade 3 nausea. No treatment-related deaths were observed.

Further analysis with a larger patient population is required to understand the response of patients with leptomeningeal carcinomatosis to T-DXd treatment, the authors concluded.

References

  1. Vaz Batista M, Pérez-García J, Garrigós L, et al. Trastuzumab deruxtecan in patients with HER2[+] or HER2-low advanced breast cancer and pathologically confirmed leptomeningeal carcinomatosis: results from cohort 5 of the DEBBRAH study. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract PS11-05.
  2. Pérez-García JM, Vaz Batista M, Cortez P, et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial. Neuro Oncol. 2023;25(1):157-166. doi:10.1093/neuonc/noac144
Related Videos
Collaboration among nurses, social workers, and others may help in safely administering outpatient bispecific T-cell engager therapy to patients.
Nurses should be educated on cranial nerve impairment that may affect those with multiple myeloma who receive cilta-cel, says Leslie Bennett, MSN, RN.
Treatment with cilta-cel may give patients with multiple myeloma “more time,” according to Ishmael Applewhite, BSN, RN-BC, OCN.
Nurses may need to help patients with multiple myeloma adjust to walking differently in the event of peripheral neuropathy following cilta-cel.
Tailoring neoadjuvant therapy regimens for patients with mismatch repair deficient gastroesophageal cancer represents a future step in terms of research.
Not much is currently known about the factors that may predict pathologic responses to neoadjuvant immunotherapy in this population, says Adrienne Bruce Shannon, MD.
Data highlight that patients who are in Black and poor majority areas are less likely to receive liver ablation or colorectal liver metastasis in surgical cancer care.
Findings highlight how systemic issues may impact disparities in outcomes following surgery for patients with cancer, according to Muhammad Talha Waheed, MD.
Pegulicianine-guided breast cancer surgery may allow practices to de-escalate subsequent radiotherapy, says Barbara Smith, MD, PhD.
Adrienne Bruce Shannon, MD, discussed ways to improve treatment and surgical outcomes for patients with dMMR gastroesophageal cancer.
Related Content