The primary objective of this study is to investigate the efficacy and safety of a fasting-mimicking diet (FMD) intervention combined with standard neoadjuvant chemoimmunotherapy in early-stage or locally advanced triple-negative breast cancer (TNBC).
Despite the significantly superior efficacy of neoadjuvant chemoimmunotherapy, a considerable proportion of early-stage treated triple-negative breast cancer (TNBC) patients ultimately experience recurrence, particularly those who do not achieve pathological complete response (pCR) after surgery. Therefore, there is an urgent need to develop new and effective treatment strategies to improve outcomes for TNBC patients. Additionally, selecting patients who are more likely to benefit from neoadjuvant chemotherapy combined with immunotherapy remains a clinical challenge. The fasting-mimicking diet (FMD) is a strictly calorie-restricted, low-sugar, low-protein, and high-fat dietary regimen that shares metabolic and anti-tumor effects with water-only fasting while reducing the risk of severe adverse reactions, leading to extensive exploration in both preclinical and clinical settings. Numerous clinical trials in breast cancer and various other cancers have investigated FMD, consistently demonstrating that FMD enhances the efficacy of standard anti-tumor therapies with a favorable safety profile. Furthermore, FMD has shown potent immunomodulatory effects in both in vivo studies and cancer patients, with the activation of anti-tumor immunity being a key mechanism underlying the anti-cancer effects of FMD alone or in combination with chemotherapy. Based on the above research background, this study focuses on operable early-stage or locally advanced triple-negative or near-triple-negative breast cancer. Patients will receive neoadjuvant standard chemotherapy combined with immunotherapy alongside FMD dietary intervention, aiming to explore the efficacy and safety of FMD dietary intervention in combination with standard neoadjuvant therapy for breast cancer patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
80
The Fasting-Mimicking Diet (FMD) will be administered every three weeks for a maximum of 8 consecutive cycles, unless side effects necessitate its temporary or permanent discontinuation. Each FMD cycle will consist of a specific FMD regimen for five consecutive days, repeated every three weeks. The FMD regimen is a plant-based, low-calorie (approximately 738 kcal on Day 1; approximately 536 kcal on Days 2 to 5), low-protein, low-carbohydrate diet. All patients will follow the identical prescribed FMD regimen. No modifications or personalization to the prescribed FMD plan is permitted. The first FMD cycle will commence two days before the administration of the first cycle of chemoimmunotherapy, be applied on the day of chemotherapy, and continue for two additional days after chemotherapy concludes.
All enrolled patients received standard preoperative chemotherapy combined with anti-PD-1 therapy. The neoadjuvant regimens were guideline-recommended protocols: TP×4-AC×4 combined with PD-1 inhibitor, TP plus PD-1 inhibitor, or PD-1 inhibitor combined with other taxane-based regimens. * T: Taxanes, including docetaxel, nab-paclitaxel, and paclitaxel. * P: Platinum agents. * A: Anthracyclines, including epirubicin, pirarubicin, and doxorubicin. * C: Cyclophosphamide.
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
Total pathological complete response (pCR) rate
The number of patients with pCR out of the total number of participants using a definition of ypT0/Tis ypN0 after neoadjuvant therapy and surgery.
Time frame: One week post-operation for the last enrolled patient
Rate of Residual Cancer Burden (RCB) of 0-1
The number of patients with RCB of 0-1 after neoadjuvant therapy and surgery.
Time frame: One week post-operation for the last enrolled patient.
Objective Response Rate (ORR)
The number of patients with complete response and partial response out of the total number of participants
Time frame: Two weeks after the end of the final cycle (each cycle is 21 days) for the last enrolled patient.
Event-Free Survival (EFS)
EFS was defined as the time from registration to disease progression (local relapse or distant metastases) or death from any cause, whichever came first
Time frame: Three years after the last patient is enrolled
Adverse events (AEs)
Adverse events (AEs) were graded according to NCI CTCAE v5.0.
Time frame: One year after the last patient is enrolled
Change in Quality of Life (QoL) scores on the EORTC QLQ-C30 questionnaire
Scores obtained on the scales of the EORTC QLQ-C30. Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
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In the neoadjuvant phase, toripalimab (anti-PD-1) was dosed intravenously at 240 mg on day 1 of every 21-day cycle.
Time frame: From baseline to 3 years after surgery
Change in Quality of Life (QoL) scores on the EORTC QLQ-BR 23 questionnaire
This EORTC breast cancer specific QLQ-BR23 questionnaire is intended to supplement the QLQ-C30. The QLQ-BR23 contains 23 items incorporating five multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning. In addition, single items assess sexual enjoyment, hair loss and future perspective. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. For all items but sexual functioning and sexual enjoyment, higher scores indicate more severe symptoms.
Time frame: From baseline to 3 years after surgery