Metronomic Capecitabine Plus Aromatase Inhibitor as Initial Therapy in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: The Phase III MECCA Trial

Author(s): Ruo-Xi Hong, MD¹; Fei Xu, MD¹; Wen Xia, MD¹; Yue-E Teng, MD²; Qu-Chang Ouyang, MD³; Qiu-Fan Zheng, MD¹; Zhong-Yu Yuan, MD¹; Dong-Shao Chen, MD¹; Kui-Kui Jiang, MD¹; Ying Lin, MD⁴; Zhen Dai, MSc⁵; Xin-Lan Liu, MD⁶; Qian-Jun Chen, MD⁷; Xin-Hong Wu, MD⁸; Yan-Xia Shi, MD¹; Jia-Jia Huang, MD¹; Xin An, MD¹; Cong Xue, MD¹; Xi-Wen Bi, MD¹; Mei-Ting Chen, MD¹; Hui Li, MD⁹; He-Rui Yao, MD¹⁰; Guo-Rong Zou, MD¹¹; Heng Huang, MD¹²; Jing-Min Zhang, MD¹; Shu-Sen Wang, MD¹

Source: https://doi.org/10.1200/JCO.24.00938

Dr. Maen Hussein's Thoughts

Metronomic dose: low dose cytotoxic therapy at high frequency was studied in combination with an AI (cape at 500mg TID) and showed superiority over AI single agent, this may be an option for patients not tolerating CKD4/6 inhibitors.

PURPOSE

The effects of metronomic chemotherapy plus endocrine therapy have yet to be elucidated through a randomized phase III clinical trial.

METHODS

Randomized clinical trials were conducted at 12 centers in China from August 22, 2017, to September 24, 2021, and the final follow-up date was August 25, 2023. Patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer (MBC) who had no previous systemic therapy in the metastatic setting were enrolled. Participants were 1:1 assigned to receive either metronomic capecitabine plus an aromatase inhibitor (AI) or AI alone. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate, disease control rate (defined as disease controlled for ≥24 weeks), and safety.

RESULTS

A total of 263 patients were randomly assigned, among which 254 patients formed the full analysis set. At the median follow-up time of 50.7 months, 203 PFS events occurred. The metronomic capecitabine plus AI arm exhibited a median PFS of 20.9 months compared with 11.9 months in the AI arm (hazard ratio [HR], 0.58 [95% CI, 0.43 to 0.76]). The median OS was not reached in the combination arm and was 45.1 months in the AI arm (HR, 0.58 [95% CI, 0.37 to 0.93]). The most common adverse events were palmar-plantar erythrodysesthesia and peripheral neuropathy; grade 3 events occurred in 15.1% of the patients receiving combination treatment.

CONCLUSION

The MECCA trial demonstrated a significant improvement in PFS and OS with first-line metronomic capecitabine plus AI compared with AI alone in patients with hormone receptor-positive+/HER2-negative MBC. Both treatment arms exhibited tolerable safety profiles consistent with previous reports.

Author Affiliations

¹Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China;²Department of Breast Internal Medicine, The First Hospital of China Medical University, Shenyang, China;³Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha, China;⁴Breast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;⁵Chengdu Center for Disease Control and Prevention, Chengdu, China;⁶Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan, China;⁷Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China;⁸Department of Breast Cancer, Hubei Cancer Hospital, Wuhan, China;⁹Department of Breast Surgery, Sichuan Cancer Hospital, Chengdu, China;¹⁰Breast Tumor Centre, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;¹¹Department of Oncology, Panyu District Cancer Institute, Panyu Central Hospital, Guangzhou, China;¹²Department of Breast Surgery, Lianjiang People’s Hospital, Lianjiang, China

Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer

ASCENT-03 shows that in first-line, PD-1/PD-L1–ineligible advanced TNBC, sacituzumab improves PFS to 9.7 vs 6.9 months and extends median duration of response (DOR) to 12.2 vs 7.2 months, with similar overall response rate (ORR) (48% vs 46%) and immature overall survival (OS) (21.5 vs 20.2 months) Grade ≥3. Adverse events (AEs) were comparable (66% vs 62%), but sacituzumab had more neutropenia and diarrhea, fewer discontinuations (4% vs 12%), and early-cycle infection-related deaths in patients without primary G-CSF. For PD-1/PD-L1–ineligible mTNBC, SG offers more durable control than chemo with manageable myelosuppression — so consider SG first-line and start G-CSF early in higher-risk patients.

Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline

Guidelines for post-mastectomy radiation include patients who received neoadjuvant therapy, with or without residual disease after treatment. A good topic to review.

First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer

Our site participated in this study, where patients were tested for ESR1 mutations via circulating tumor DNA (ctDNA). Those who tested positive were switched to camizestrant (Cami), which demonstrated improved progression-free survival.

Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer

Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly utilizes the ubiquitin–proteasome system. It was compared to fulvestrant in patients who had received one prior line of hormonal therapy with a CDK4/6 inhibitor. Among patients with ESR1 mutations, Vepdegestrant demonstrated a median progression-free survival (PFS) of 5.0 months versus 2.1 months with fulvestrant. In the overall population, the median PFS was 3.8 months for Vepdegestrant and 3.6 months for fulvestrant, indicating that the drug showed particular efficacy in tumors harboring ESR1 mutations.

Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer

Elinzanitant, a neurokinin-targeted therapy, has been shown to reduce vasomotor symptoms compared to placebo. These symptoms are one of the reasons some of my patients discontinue aromatase inhibitor (AI) therapy, so Elinzanitant presents a promising alternative to help manage these side effects. Additionally, Fezolinetant is already approved and available on the market.