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Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan.

ABSTRACT: Antibody-drug conjugates have transformed the treatment of HER2+ breast and other cancers. Unfortunately, the CNS remains a sanctuary site for many such patients in part due to poor macromolecule penetration across the blood-brain tumor barrier. Trastuzumab deruxtecan (T-DXd), a high-payload antibody-drug conjugate, was recently found to improve progression-free survival in HER2+ breast cancer patients versus prior-generation trastuzumab emtansine, prompting us to evaluate CNS activity in a woman with brain-only metastatic disease. T-DXd achieved complete response despite heavy pretreatment. Three persistent, previously-irradiated lesions were biopsy-proven to represent treatment effect. Subsequent recurrence occurred upon treatment holiday; partial response was observed with rechallenge. This case suggests T-DXd is active in HER2+ breast cancer brain metastases and supports further prospective evaluation.

SUBMITTER: Moss NS

PROVIDER: S-EPMC9280405 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan.

Moss Nelson S NS Tosi Umberto U Santomasso Bianca D BD Beal Kathryn K Modi Shanu S

CNS oncology 20220608 3

Antibody-drug conjugates have transformed the treatment of HER2+ breast and other cancers. Unfortunately, the CNS remains a sanctuary site for many such patients in part due to poor macromolecule penetration across the blood-brain tumor barrier. Trastuzumab deruxtecan (T-DXd), a high-payload antibody-drug conjugate, was recently found to improve progression-free survival in HER2+ breast cancer patients versus prior-generation trastuzumab emtansine, prompting us to evaluate CNS activity in a woma ...[more]

PMID: 35674041

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Project description:BackgroundTrastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is currently unknown. No direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs in patients commencing T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd.Patients and methodsPatients with human epidermal growth factor receptor 2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinicopathological information, prior treatment, the presence or absence of central nervous system (CNS) disease, outcomes and treatment-emergent adverse events (TEAEs) were recorded.ResultsTwenty-nine female patients, with a median age of 52 years (interquartile range 44-62 years), were identified; the prevalence of BM was 41%. Median number of lines of prior therapy was 2 (range 2-6). At a median follow-up of 13.8 months, median progression-free survival (PFS) for the overall population was 13.9 months [95% confidence interval (CI) 12.4 months-not estimable (NE)], 16.1 months (95% CI 15.1 months-NE) for active BMs and 12.4 months (95% CI 8.3 months-NE) for progressive extracranial disease alone. The 12-month overall survival (OS) rate was 74% (95% CI 59% to 95%) in the overall population, and 83% (95% CI 58% to 100%) and 66% (95% CI 45% to 96%) for active BMs and extracranial disease only, respectively. Most common TEAEs were fatigue, alopecia, and constipation. In nine patients (31%, including two deaths), pneumonitis occurred.ConclusionIn this real-world population, we demonstrate T-DXd to be effective in patients with active BMs and those with progressive extracranial disease alone. PFS and OS were numerically longer in those with active BMs. These data demonstrate that patients with active BM treated with T-DXd have at least comparable outcomes to those with extracranial disease alone. The high rate of pneumonitis warrants further consideration.

Project description:BackgroundBrain metastases (BMs) are common in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer, increasing morbidity and mortality. Systemic therapy for BMs can be effective, with the triple combination of trastuzumab, capecitabine, and tucatinib being a potential standard. More recently, intracranial activity of antibody-drug conjugates has been reported, but the size of individual studies has been small. Therefore, this patient-level pooled analysis was conducted.Patients and methodsThis is a patient-level pooled analysis of the prospective phase II DEBBRAH and TUXEDO-1 trials and the retrospective DFCI/Duke/MDACC cohort. Patients with evaluable active BMs (defined as newly diagnosed and untreated or progressing with measurable tumor-related size after previous local therapy) from HER2-positive breast cancer (BC) and treated with trastuzumab deruxtecan (T-DXd) included in these studies were eligible. The primary endpoint was intracranial objective response rate (ORR-IC) by Response Assessment in Neuro-Oncology (RANO)-BM criteria.ResultsOverall, 37 patients were assessable for intracranial response assessment. BMs progressing after prior local therapy were present in 64.9% of patients. The median patient age was 49.1 years. All patients had received prior trastuzumab and the median number of prior systemic treatment lines was 3 (0-13). The pooled ORR-IC by RANO-BM criteria was 64.9% [95% confidence interval (CI) 47.5% to 79.8%] with low heterogeneity observed between the studies included. The clinical benefit rate by RANO-BM was 81.1% (95% CI 64.8% to 92.0%). The median progression-free survival was 13.3 months (95% CI 8.4-22.6 months) and the median overall survival was 22.5 months (95% CI 14.9 months-not achieved) with high heterogeneity between studies and numerically longer in patients with few prior treatment lines. Quality of life remained stable throughout treatment, with no new safety concerns.ConclusionsThis patient-level pooled analysis of DEBBRAH, TUXEDO-1, and the DFCI/Duke/MDACC cohort indicates clinically relevant intracranial activity of T-DXd in patients with active HER2-positive BC, BMs, and extensive systemic pretreatment. The results therefore support the use of T-DXd when clinically indicated irrespective of BMs.

Project description:Objective:To explore the risk factors for postoperatively pathological lymph node metastasis in patients with clinical T2N0M0 stage prostate cancer (PCa). Methods:We retrospectively analyzed clinicopathological data of 316 patients with clinical T2 stage PCa and preoperative negative lymph nodes [LN(-)] indicated by imaging (cT2N0M0) between January 2014 and May 2019. Multivariate logistic regression analysis was performed to determine risk factors for postoperatively pathological pLN(+) in patients with cT2N0M0 stage PCa. Spearman correlation analysis was used to explore the relationship between tumor burden and Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. Results:A total of 45 patients (14.2%) were confirmed by postoperative pathology to have LN metastasis. Univariate analysis indicated that total prostate-specific antigen (tPSA), PI-RADS v2 score, postoperative Gleason grade group (GGG), intraductal carcinoma of the prostate (IDC-P), clinical T2 substaging, and postoperative pathological tumor burden were risk factors for pLN(+) in all patients. Multivariate analysis showed that tPSA and postoperative GGG were risk factors for pLN(+) in all patients. Univariate analysis revealed that tPSA, PIRADS v2 score, clinical T2 substaging, IDC-P, postoperative pathological tumor burden, and postoperative GGG were risk factors for pLN(+) in patients with GGG ? 3. Multivariate analysis suggested that tPSA, PI-RADS v2 score, clinical T2 substaging, postoperative pathological tumor burden, and GGG were risk factors for pLN (+) in patients with GGG ? 3. Spearman correlation analysis showed that PI-RADS v2 score was positively correlated with clinical T2 substaging and postoperative pathological tumor burden. Conclusion:There was a high risk of LN metastasis in patients with cT2 PCa if they had high preoperative tPSA or high postoperative GGG. Patients with cT2 PCa and GGG ? 3 had a high risk of LN metastasis if they had high PI-RADS v2 score, high preoperative clinical stage or high postoperative pathological tumor burden. PI-RADS v2 score predicted tumor burden well in patients with GGG ? 3.

Dataset Information

Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan.

Publications

Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan.

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