Abstract P1-16-01: Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer: A randomized, open-label, multicenter, phase II trial (KCSG-BR15-17)
Authors: Lee Dae-Won , Park Yeon Hee , Jung Kyung-Hae , Lee Kyung-Hun , Lee Keun Seok , Sohn Joohyuk , Ahn Hee Kyung , Jeong Jae Ho , Koh Su-Jin , Kim Jee Hyun , Kim Han Jo , Lee Kyoung Eun , Kim Hee-Jun , Lee Ki Hyeong , Park Kyong Hwa , Lee Jieun , Won Hye Sung , Kim Tae-Yong , Im Seock-Ah 
Published: March 2022

Abstract
Background: Anthracyclines and taxanes are the preferred regimens for patients with advanced breast cancer and are usually introduced in earlier lines. Tumors refractory to anthracycline and taxanes are aggressive and often show rapid progression. Although single sequential chemotherapy is standard of care, combination chemotherapy is required for patients with rapid progression. Development of effective and tolerable combination regimens focused on these patients is clinically relevant. Methods: This randomized, open-label, phase II trial was conducted in 16 centers in Korea. Eligible patients were women aged 18 years or older with advanced or metastatic breast cancer previously treated with anthracycline and taxanes. A maximum of three previous chemotherapy regimens for metastatic disease were allowed. Patients were randomly assigned in a 1:1 ratio to receive vinorelbine monotherapy (25 mg/m2 days 1 and 8) or pemetrexed (500 mg/m2 day 1) plus vinorelbine (25 mg/m2 days 1 and 8) in a 21-day cycle until disease progression or unacceptable toxicity. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival, safety, and quality of life (QoL). Results: From March 2017 through August 2019, a total of 125 patients were enrolled. Sixty-two patients were assigned to pemetrexed plus vinorelbine and 63 were assigned to vinorelbine monotherapy. Baseline characteristics and demographics were well-balanced between the two treatment groups. Overall, hormone receptor was positive in 58.4% of patients and HER2 was positive in 6.4% of patients. Fifty-six percent of patients received 2 or 3 line of previous palliative chemotherapy and 41% of patients received previous endocrine therapy of palliative purpose. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine monotherapy (5.7 vs. 1.5 months, hazard ratio 0.542 [95% CI 0.374 - 0.786], p &lt; 0.001). Prolonged PFS with pemetrexed plus vinorelbine compared to vinorelbine monotherapy was consistent across all patient subgroups, regardless of patient’s hormone receptor status, prior capecitabine use, prior lines of palliative chemotherapy, and metastases sites. ORR was numerically higher (15.0% vs. 9.8%) and disease control rate was significantly higher (78.3% vs. 45.9%) in patients treated with pemetrexed plus vinorelbine compared to vinorelbine monotherapy. Febrile neutropenia (16.1% vs. 4.9%, p = 0.043), liver enzyme elevation (25.8% vs. 11.5%, p = 0.042), and anemia (29.0% vs. 9.8%, p = 0.007) was more frequent in the combination arm, but the toxicities were generally manageable. There was no treatment related death and only one patient in the monotherapy arm discontinued the treatment due to febrile neutropenia. There was no difference in QoL as measured by EORTC QLC-C30 and QLQ-BR23. Conclusions: Pemetrexed plus vinorelbine led to longer progression-free survival compared to vinorelbine monotherapy with manageable toxicities. We believe pemetrexed plus vinorelbine could be considered as a treatment option in patients with advanced breast cancer.
Table 1.Best tumor responseTotal (N = 123)Vinorelbine single (N = 61)Pemetrexed plus vinorelbine (N = 62)P-ValueComplete response0 (0.0%)0 (0.0%)0 (0.0%)0.001Partial response15 (12.4%)6 (9.8%)9 (15.0%)Stable disease60 (49.6%)22 (36.1%)38 (63.3%)Progressive Disease46 (38.0%)33 (54.1%)13 (21.7%)
Citation Format: Dae-Won Lee, Yeon Hee Park, Kyung-Hae Jung, Kyung-Hun Lee, 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, Ki Hyeong Lee, Kyong Hwa Park, Jieun Lee, Hye Sung Won, Tae-Yong Kim, Seock-Ah Im. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer: A randomized, open-label, multicenter, phase II trial (KCSG-BR15-17) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-16-01.