This 2017 article’s real contribution here isn’t the narrative review—which, as is too selective to be high-quality—but the new VICTOR-2 subgroup data. While a 35.7% Clinical Benefit Rate in an elderly (median age 69) metastatic TNBC population is certainly interesting, it’s from a tiny, single-arm cohort of 28 patients.

This paper highlights metronomic chemotherapy as a potential palliative option, especially for frail or elderly patients where standard, max-dose chemo is not a viable option due to toxicity. 

Clinical Bottom Line

This 2017 article by Cazzaniga et al. provides a narrative review of the sparse preclinical and clinical data available for metronomic chemotherapy (mCHT) in triple-negative breast cancer (TNBC). The authors conclude that while evidence is very limited—drawn mostly from small Phase II trials or subgroup analyses—some promising results exist, particularly as a potential treatment option for specific populations like the elderly.

Crucially, this paper is not a systematic review and its conclusions are based on a selective literature search. Its most novel contribution is the first-time reporting of prospective data from the TNBC subgroup (n=28) of the authors’ own VICTOR-2 Phase II trial, which showed a clinical benefit rate of 35.7% with a metronomic combination of vinorelbine and capecitabine.

Results

Metronomic chemotherapy is defined as the minimum biologically effective dose of a chemotherapy agent given continuously with no prolonged drug-free breaks. The review summarizes data across three setting¹s:

Preclinical Data

• One study in a TNBC mouse model found that metronomic topotecan combined with pazopanib significantly enhanced antitumor activity and prolonged survival compared to either drug alone.

(Neo)Adjuvant Setting

• The review highlights mixed results from a few trials.

• The IBCSG 22-00 trial found no statistically significant benefit for metronomic cyclophosphamide and methotrexate (CM) maintenance in the overall TNBC population.

• In contrast, a study by Nasr et al. concluded that extended adjuvant metronomic CM did achieve a significant improvement in survival and was well-tolerated.

• The authors of this review state their opinion that mCHT should not be adopted in the adjuvant setting without stronger preclinical data.

Metastatic Setting

• Data is noted as being very scarce, with most trials enrolling HER2-negative patients and reporting on TNBC patients only in subgroup analyses.

VICTOR-2 Subgroup Analysis (New Data)

The review presents new data on 28 TNBC patients from the VICTOR-2 study, a Phase II, single-arm trial evaluating metronomic vinorelbine (40 mg three times/week) and capecitabine (500 mg three times/day).

• Population: Median age was 69 years. 82.1% had visceral involvement.

• Efficacy:

  • Clinical Benefit Rate (CBR): 35.7%

  • Disease Control Rate (DCR): 53.6%

  • Median PFS: 4.7 months

• Toxicity: Severe (Grade 3/4) toxicity did not exceed 8% and was mainly hematologic.

Critical Appraisal

This article is a hybrid narrative review and primary data report. Its structure has significant limitations as a review.

• Certainty of Evidence: The overall certainty of the evidence presented for mCHT in TNBC is Very Low. This rating is based on the review’s reliance on a small number of preclinical studies, subgroup analyses, and small, non-randomized Phase II studies.

• Search Strategy & Reporting: The article does not follow PRISMA guidelines for systematic reviews.

  • Search Strategy: This is a significant limitation. The search was restricted to only one database (PubMed) using three keywords, creating a high risk of selection bias.

  • Bias Assessment: The authors do not provide a formal risk of bias assessment for the included studies.

• Primary Contribution: The review itself is limited. The article’s most significant contribution is the inclusion of the first prospective data (though from a small, single-arm subgroup) on metronomic vinorelbine and capecitabine in metastatic TNBC patients.

Article Citation

• Title: Metronomic Chemotherapy in Triple-Negative Metastatic Breast Cancer: The Future Is Now?

• Authors: M. E. Cazzaniga, L. Cortesi, A. Ferzi, L. Scaltriti, F. Cicchiello, M. Ciccarese, S. Della Torre, F. Villa, M. Giordano, C. Verusio, M. Nicolini, A. R. Gambaro, L. Zanlorenzi, E. Biraghi, E. Casini, L. Legramandi, and E. Rulli

• Journal: International Journal of Breast Cancer

• Year: 2017

• DOI: 10.1155/2017/1683060