LONG-TERM FOLLOW-UP STUDY OF EARLY STAGE BREAST CANCER PATIENTS INCLUDED IN GEICAM STUDIES

The primary objective of this study is to describe the long-term evolution of patients with **invasive breast cancer** in early stages who were included in GEICAM neoadjuvant and adjuvant clinical trials. This involves evaluating the frequency, type, and location of the first relapse. Understanding these factors is clinically relevant as it can inform treatment strategies and improve patient management by identifying patterns of disease progression.

Secondary objectives include assessing:

• Overall survival, which provides insights into the long-term efficacy of treatments.
• Disease-free survival in adjuvant patients, indicating the period patients remain free from cancer post-treatment.
• Event-free survival in neoadjuvant patients, reflecting the time until any cancer-related event occurs.
• Cause of death, which helps in understanding mortality factors associated with the disease.

The clinical trial involves **patients with invasive breast cancer in early stages**. The study population consists exclusively of female subjects, with an age range that includes adults and older adults. The trial does not include a vulnerable population. The total number of participants is not specified, as the sponsor has not provided this information. Participants were selected based on their inclusion in previous neoadjuvant and adjuvant clinical trials with GEICAM's participation. Individuals who have participated in other clinical trials are also eligible, provided their death or loss of contact has not been previously recorded in the original study databases. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The focus is on understanding the long-term evolution of these patients, specifically examining the frequency, type, and location of the first relapse.

The clinical trial is designed to evaluate the long-term evolution of patients with **invasive breast cancer** in early stages who have been included in GEICAM neoadjuvant and adjuvant clinical trials. This study is a Phase IV, low-intervention trial, focusing on the frequency, type, and location of the first relapse. The trial employs a **randomized, double-blind, controlled** design to ensure the reliability and validity of the results. The estimated duration of the trial is from November 15, 2018, to November 15, 2048, allowing for comprehensive long-term follow-up.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as previous participation in GEICAM trials and the absence of recorded death or contact loss in original study databases. Follow-up visits will be scheduled to monitor the primary endpoints, which include the dates of disease relapse and second primary tumors, as well as Event Free Survival (EvFS) in neoadjuvant studies and Event Free Survival (EFS) in adjuvant studies. Secondary endpoints will assess overall survival and the relation of death to breast cancer. The end-of-study visit will conclude the participant's involvement, summarizing the collected data and outcomes.

The expected length of participant involvement varies, with the maximum treatment period for the investigational products ranging from 6 to 112 weeks, depending on the specific medication administered. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial aims to provide valuable insights into the long-term management and outcomes of early-stage breast cancer, contributing to the optimization of therapeutic strategies.

The clinical trial involves the administration of several **experimental medications**. **Xeloda** 500 mg film-coated tablets, containing the active substance **capecitabine**, are administered orally. The maximum daily dose is 500 mg, with a treatment period of up to 24 weeks. **Gemcitabina Accord** 2000 mg, a powder for solution for infusion containing **gemcitabine**, is administered intravenously. The maximum daily dose is 2000 mg/m², with a treatment period of up to 12 weeks.

**Paclitaxel Hospira** 6 mg/ml, a concentrate for solution for infusion containing **paclitaxel**, is administered intravenously. The maximum daily dose is 150 mg, with a treatment period of up to 12 weeks. **Aromasil** 25 mg coated tablets, containing **exemestane**, are administered orally. The maximum daily dose is 4500 mg, with a treatment period of up to 6 months.

**Faslodex** 250 mg solution for injection, containing **fulvestrant**, is administered intramuscularly. The maximum daily dose is 250 mg, with a treatment period of up to 36 months. **Zoladex** 3.6 mg implant, containing **goserelin acetate**, is administered subcutaneously. The maximum dose is 21.6 mg over a 6-month period.

**Abraxane** 5 mg/ml powder for dispersion for infusion, containing **paclitaxel albumin-bound**, is administered intravenously. The maximum daily dose is 150 mg, with a treatment period of up to 112 weeks. **TAXOTERE** 20 mg/0.5 ml concentrate and solvent for solution for infusion, containing **docetaxel**, is administered intravenously. The maximum daily dose is 75 mg, with a treatment period of up to 18 weeks.

**Myocet liposomal** 50 mg powder, dispersion and solvent for concentrate for dispersion for infusion, containing **doxorubicin hydrochloride**, is administered intravenously. The maximum daily dose is 75 mg, with a treatment period of up to 126 weeks. **Lapatinib** film-coated tablets are administered orally, with a maximum daily dose of 1250 mg over a 12-week period.

**Ofev** 100 mg soft capsules, containing **nintedanib**, are administered orally. The maximum daily dose is 400 mg, with a treatment period of up to 84 weeks. **Carboplatin** 10 mg/ml concentrate for solution for infusion is administered intravenously. The maximum daily dose is 24 mg/ml, with a treatment period of up to 12 weeks.

**Herceptin** 150 mg powder for concentrate for solution for infusion, containing **trastuzumab**, is administered intravenously. The maximum daily dose is 150 mg, with a treatment period of up to 12 weeks. Participant compliance is monitored through regular assessments and adherence checks throughout the study duration.

Efficacy in this clinical trial will be assessed using specific primary and secondary endpoints. The primary endpoints include the dates of disease relapse, whether local, regional, or distant, and the occurrence of second primary tumors. Additionally, **Event Free Survival (EvFS)** will be evaluated in neoadjuvant studies, and **Event Free Survival (EFS)** will be assessed in adjuvant studies. Secondary endpoints will focus on the date of death and its relation to breast cancer, as well as **Overall Survival (OS)**.

The collection and analysis of these endpoints will be conducted throughout the trial duration, with data being gathered at various timepoints as specified in the study protocol. The trial aims to describe the long-term evolution of patients with invasive breast cancer in early stages, who were included in GEICAM neoadjuvant and adjuvant clinical trials. The frequency, type, and location of the first relapse will be studied to provide comprehensive insights into the disease progression and patient outcomes.