Efficacy and Safety of Extended-Dose Interval Immunotherapy Versus Standard-Dose Interval Immunotherapy for Advanced Triple-Negative Breast Cancer: A Multicenter Randomized Controlled Clinical Trial
Triple-negative breast cancer (TNBC), defined by the lack of ER, PR and HER2 expression, is refractory to endocrine therapy and anti-HER2 agents. Chemotherapy was once the mainstay for advanced TNBC, but its limited efficacy necessitates optimized therapeutic strategies. TNBC's high TIL infiltration and elevated PD-L1 expression confer sensitivity to immune checkpoint inhibitors (ICIs), with ICI-chemotherapy combinations initially establishing first-line standard status. Emerging clinical evidence shows that ICI-antibody-drug conjugate (ADC) combinations outperform ICI-chemotherapy regimens, yet immune-related adverse events (irAEs) remain a critical clinical challenge. Expert consensus recommends continuing ICI therapy in advanced TNBC patients achieving CR, PR or SD after ICI-based combination therapy until disease progression or intolerable toxicity. Mechanistically, once ICIs reach target receptor saturation, dose escalation or high-frequency administration fails to boost efficacy but raises toxicity risk. Thus the investigators hypothesize that an ICI maintenance strategy with fixed dose and extended intervals can preserve efficacy, reduce toxicity, improve patient compliance, enhance quality of life and alleviate economic burden for advanced TNBC patients with CR/PR/SD after ICI-chemotherapy or ICI-ADC treatment.
• Voluntary consent to participate in this study and signing of the informed consent form.
• The age of the signatory of the informed consent form should be ≥18 years old and ≤70 years old.
• Advanced (locally recurrent inoperable or metastatic) TNBC confirmed by histology or cytology, defined as ER-negative, PR-negative, and HER2-negative.
• PD-L1 IHC detection in tumor tissue with a CPS score ≥1.
• Have received first-line standard immunotherapy combined with chemotherapy or immunotherapy combined with ADC and completed 6 cycles, with the last dose administered no more than 28 days before randomization.
• The therapeutic efficacy was confirmed as CR, PR or SD after 6-cycle standard treatment according to the RECIST v1.1 criteria.
• Plan to continue receiving immunotherapy.
• An Eastern Cooperative Oncology Group performance-status score of 0 or 1.
• The expected survival period exceeds 12 weeks.
⁃ Adequate organ function:.
⁃ No mental or intellectual abnormalities.
⁃ Willing and able to comply with the trial protocol during the trial period.
⁃ Female subjects of childbearing potential must agree to use highly effective contraceptive measures starting at least 7 days before the first dose and continuing until 24 weeks after the last dose. The serum pregnancy test result must be negative within 7 days prior to the first dose.