Association of Pembrolizumab Infusion Time and Efficacy in Patients With Non-metastatic Triple-negative Breast Cancer (TNBC) Treated With Neoadjuvant Chemotherapy and Immunotherapy

NCT06418139 | Not Yet Recruiting

• 1 other identifier: APHP240393
• Study Type: observational
• Target: 450
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Triple negative breast cancer (TNBC) is characterized by an aggressive biological behaviour responsible for higher risk of recurrence and shorter median survival. Pembrolizumab, an immune checkpoint inhibitor (ICI) targeting programmed death (PD-1), in association to chemotherapy showed improvement of event-free survival in patients with previously untreated stage II or III TNBC and has been approved in Europe since March 2022 for this indication (KEYNOTE-522). Circadian timing system controls many various biological functions in humans including xenobiotic metabolism and elimination, immune functions, cell cycle event and apoptosis. Thus, chronotherapeutic approaches have shown improved efficacy and tolerability in the treatment of different types of cancer, notably in colorectal cancer. Pronounced circadian rhythms in immune functions are generated by cell-autonomous molecular clocks in T and B lymphocytes, macrophages, neutrophils, and dendritic cells. Recently, first evidence of the effect of timing infusion of immune checkpoint inhibitors on prognosis of patients with cancer has been reported in several retrospective trials. Landre et al.'s meta-analysis of 7 retrospective studies including 1019 patients who had metastatic cancer was presented at the American Society of Clinical Oncology (ASCO) meeting in 2023. An early time-of-day ICI infusions was associated with an increase overall survival (HR: 0.49, \[95% CI: 0.36-0.69\] p \< 0.0001). Objectives: The aim is to analyze immunotherapy infusion timing impact on histological response, toxicity and Event Free-Survival (EFS) in patients with TNBC treated with Neo-Adjuvant Chemotherapy (NAC) associated with pembroluzimab. Measure of histological response is the primary objective determined by Residual Cancer Burden (RCB). Secondary endpoints are Event free Survival (EFS), calculated from the date of diagnosis to invasive local, regional, or metastatic relapse, contralateral breast cancer, or death from any cause), toxicity which is assessed by recording adverse events (CT-CAE v5) occurring from start of treatment to last course. Methods: Data from patients with histologically proven early TNBC treated from July 2021 to May 2023 with the association of Pembrolizumab, Paclitaxel Carboplatine followed with Pembrolizumab Cyclophosphamide Epirubicine (according to KEYNOTE 522 study) will be collected. Dosing times of each Pembrolizumab and chemotherapy infusions given to consecutive patients as a neoadjuvant standard treatment, associated with chemotherapy, for early TNBC are retrieved from hospital records. Adjuvant Pembrolizumab timing intake will be also recorded as EFS is a secondary endpoint. Statistics: First, median clock hour of all infusions of Pembrolizumab will be determined. Then, patients will be dichotomized between "morning' and 'afternoon' groups using 2 cut-offs: 1/ median clock of all infusions of pembrolizumab ('morning group' will include the patients who receive the majority of Pembrolizumab infusions before this median clock hour and 'afternoon group', patients who receive the majority of Pembrolizumab infusions after this median clock hour) and 2/ cut-off optimizing differences of RCB between two groups. Patient's characteristics, toxicities, tumor response and EFS will be compared.

Conditions

Non-Metastatic Breast Carcinoma

Keywords

Non metastatic Triple-negative breast cancer; Triple-negative breast cancer; Chronotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Residual cancer burden class (RCB)

  RCB is studied after neoadjuvant treatment (Symmans et al. 2007)

  Up to 36 months

Secondary Outcomes (9)

• Number of immune adverse events

  Up to 36 months

• Histological Complete Response (hCR) rate versus invasive residual disease rate

  Up to 36 months

• Tumor-infiltrating lymphocyte (TIL) levels

  Up to 36 months

• Progression-free survival

  At 2 years

• Number of Pembrolizumab infusions performed

  Up to 36 months

Study Arms (2)

Morning group

Other: No intervention

Afternoon group

Other: No intervention

Interventions

No intervention OTHER

No intervention added by the study

Afternoon group; Morning group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Female with high-risk early triple-negative breast cancer treated with neoadjuvant chemotherapy combined with pembrolizumab

You may qualify if:

• Female sex
• Age ≥ 18 years-old
• Previously untreated histologically proven triple-negative breast cancer (RE \< 10%, RP \< 10%, Her-2 negative)
• No metastatic
• Having at least one injection of pembrolizumab associated with chemotherapy
• Pembrolizumab injection schedule correctly reported by the nurse in charge of the patient

You may not qualify if:

• Metastatic disease

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Sylvie Giacchetti, Dr

CONTACT

+33142499785; sylvie.giacchetti@aphp.fr

Jérôme Lambert, Pr

CONTACT

+33142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2024
• First Posted: May 16, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 16, 2024

Record last verified: 2024-04