A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.

Abstract

BACKGROUND:

Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab.

METHODS:

This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR).

RESULTS:

A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively.

CONCLUSIONS:

The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC.

PLAIN LANGUAGE SUMMARY:

Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.

• Authors: Jiyun Lee, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Seyoung Seo, Sung-Bae Kim, Ji-Won Kim, Keun-Wook Lee, Eun Joo Kang, Ju Won Kim, Yoon Ji Choi, Byoung-Yong Shim, Ho-Jung An, Lee Chun Park, Seong Hoon Shin, Jae-Joon Kim, So Yeon Oh, Min Kyoung Kim, Myung-Ju Ahn
• Journal: Cancer (Cancer) Vol. 129 Issue 19 Pg. 2966-2974 (10 01 2023) ISSN: 1097-0142 [Electronic] United States
• PMID: 37246414 (Publication Type: Multicenter Study, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 American Cancer Society.

Chemical References

• Docetaxel
• Micelles
• Antibodies, Monoclonal, Humanized
• Trastuzumab
• Receptor, ErbB-2

Topics

• Humans
• Female
• Docetaxel (therapeutic use)
• Micelles
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Trastuzumab (therapeutic use)
• Receptor, ErbB-2 (genetics, metabolism)
• Carcinoma, Ductal
• Salivary Glands (metabolism)
• Breast Neoplasms (drug therapy)