Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open-label, multicenter, phase II trial

Dae-Won Lee; Kyung Hae Jung; Kyung-Hun Lee; Yeon Hee Park; Keun Seok Lee; Joohyuk Sohn; Hee Kyung Ahn; Jae Ho Jeong; Su-Jin Koh; Jee Hyun Kim; Han Jo Kim; Kyoung Eun Lee; Hee-Jun Kim; Yae-Won Yang; Kyong Hwa Park; Jieun Lee; Hye Sung Won; Tae-Yong Kim; Seock-Ah Im

doi:10.1016/j.ejca.2023.113456

Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open-label, multicenter, phase II trial

Eur J Cancer. 2024 Jan:197:113456. doi: 10.1016/j.ejca.2023.113456. Epub 2023 Nov 20.

Authors

Dae-Won Lee¹, Kyung Hae Jung², Kyung-Hun Lee³, Yeon Hee Park⁴, Keun Seok Lee⁵, Joohyuk Sohn⁶, Hee Kyung Ahn⁷, Jae Ho Jeong², Su-Jin Koh⁸, Jee Hyun Kim⁹, Han Jo Kim¹⁰, Kyoung Eun Lee¹¹, Hee-Jun Kim¹², Yae-Won Yang¹³, Kyong Hwa Park¹⁴, Jieun Lee¹⁵, Hye Sung Won¹⁶, Tae-Yong Kim¹⁷, Seock-Ah Im¹⁸

Affiliations

¹ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Translational Medicine, Seoul National University College of Medicine, Seoul, South Korea.
² Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
³ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea. Electronic address: kyunghunlee@snu.ac.kr.
⁴ Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea.
⁵ Center for Breast Cancer, National Cancer Center, Goyang, South Korea.
⁶ Division of Medical Oncology and Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
⁷ Division of Medical Oncology and Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
⁸ Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, Ulsan University College of Medicine, South Korea.
⁹ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Translational Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
¹⁰ Division of Oncology and Hematology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea.
¹¹ Department of Hematology and Oncology, Ewha Womans University Hospital, Seoul, South Korea.
¹² Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea.
¹³ Deparment of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea.
¹⁴ Division of Oncology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, South Korea.
¹⁵ Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
¹⁶ Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
¹⁷ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea.
¹⁸ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Translational Medicine, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea. Electronic address: moisa@snu.ac.kr.

PMID: 38104354
DOI: 10.1016/j.ejca.2023.113456

Abstract

Introduction: Metastatic breast cancer refractory to anthracycline and taxanes often shows rapid progression. The development of effective and tolerable combination regimens for these patients is needed. This phase II trial investigated the efficacy of pemetrexed plus vinorelbine in patients with metastatic breast cancer.

Methods: This randomized, open-label, phase II trial was conducted in 17 centers in Korea. Patients with advanced breast cancer who had previously been treated with anthracyclines and taxanes were randomly assigned in a 1:1 ratio to receive either vinorelbine or pemetrexed plus vinorelbine. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included the objective response rate, overall survival, safety, and quality of life.

Results: Between March 2017 and August 2019, a total of 125 patients were enrolled. After a median follow-up duration of 14.1 months, 118 progression events and 88 death events had occurred. Sixty-two patients were assigned to the pemetrexed plus vinorelbine arm, and 63 were assigned to the vinorelbine arm. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine (5.7 vs. 1.5 months, p < 0.001). The combination arm had higher disease control rate (76.8% vs. 45.9%, p = 0.001) and a tendency toward longer overall survival (16.8 vs. 10.5 months, p = 0.102). Anemia was more frequent in the pemetrexed plus vinorelbine arm per cycle compared with vinorelbine (7.9% vs. 1.9%, p < 0.001), but there was no difference in the incidence of grade 3-4 neutropenia per cycle between the pemetrexed plus vinorelbine arm and the vinorelbine single arm (14.7% vs. 19.5%, p = 0.066).

Conclusions: This phase II study showed that pemetrexed plus vinorelbine led to a longer PFS than vinorelbine. Adverse events of pemetrexed plus vinorelbine were generally manageable.

Keywords: Metastatic breast cancer; Pemetrexed; Randomized phase II trial; Vinorelbine.

Publication types

Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase II

MeSH terms

Anthracyclines / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Breast Neoplasms* / pathology
Female
Humans
Pemetrexed* / therapeutic use
Quality of Life
Taxoids / therapeutic use
Vinorelbine* / therapeutic use

Substances

Anthracyclines
Pemetrexed
Taxoids
Vinorelbine