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MEDSIR at ESMO 2021: Presentation of DEBBRAH and PATHFINDER study design

The European Society for Medical Oncology (ESMO) is a leading organization in Europe with more than 250,000 members from over 160 countries worldwide, and the unique mission to offer the best of care to cancer patients, through fostering integrated oncological care and innovative research.

ESMO congress will take place from 16 to 21 September 2021 and, for the second time, it will adopt an online format. Though virtual, this will still be considered as an invaluable platform to present promising new developments focused at

improving clinical standards in oncology.

This year, MEDSIR is presenting the study design from two trials: DEBBRAH and PATHFINDER, both sponsored and designed by MEDSIR.

DEBBRAH is an international, single-arm, open label, phase II trial evaluating activity of Trastuzumab Deruxtecan (T-DXd) in 5 different cohorts of patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Advanced Breast Cancer (ABC), presenting with brain metastases and/or leptomeningeal carcinomatosis. A total of 39 patients will be enrolled from Spain and Portugal in 5 cohorts, depending on their tumor and metastasis characteristics, to receive T-DXd intravenously on day 1 of each 21-day cycle, until disease progression, unacceptable toxicity, or consent withdrawal.

DEBBRAH is the first prospective trial to evaluate the efficacy of T-DXd in ABC patients with brain involvement, representing a good chance to introduce a valid therapeutic alternative to a large group of patients who need novel treatment options. T-DXd is a drug composed of an antibody against HER2 (called trastuzumab), linked to a topoisomerase I inhibitor compound, a cytotoxic drug which synergizes with trastuzumab against HER2+ cancer cells. T-DXd displayed a good range of activity in preclinical and clinical studies, and it is foreseen to have capacity to reach the central nervous system when the blood-brain barrier is disrupted, such as in ABC patients with brain metastasis.

This study represents a strategical opportunity for ABC patients affected by brain metastasis and/or leptomeningeal carcinomatosis, a rare complication of cancer in which the disease spreads to the meninges. No specific drugs have been approved for these patients, routinary excluded from clinical trials, and whose therapeutic options remain limited due to poor research extent in this area” affirmed Dr. Vaz-Batista, medical oncologist at Fernando Fonseca Hospital, Armadora, Portugal, and first author of the communication.

Today, DEBBRAH is open for recruitment, with 34 patients already enrolled in the study. The medical community is looking forward to the final results of the trial, to confirm whether or not, T-DXd has activity in various populations with CNS involvement, who are currently lacking a specific treatment for their advanced disease.

MEDSIR’s second study participating at ESMO is PATHFINDER: a multicenter, open-label, three-arm, phase IIa trial evaluating safety, tolerability, and preliminary efficacy of ipatasertib in combination with non-taxane chemotherapy agents for taxane-pretreated advanced or metastatic Triple-Negative Breast Cancer (TNBC) patients.

Fifty-four patients will be recruited and randomized into 3 different cohorts (18 patients/each), to be administered with ipatasertib combined with either capecitabine (Arm A), or eribulin (Arm B), or carboplatin plus gemcitabine (Arm C); three different types of non-taxane chemotherapies. The study started with an initial run-in phase for safety, to assure that all the proposed combination and doses are safe, and after, patients will continue their treatment until progression of disease, unacceptable toxicity, death, or discontinuation from treatment for any reason.

Patients with advanced TNBC are a susceptible population with a bad prognosis in the long run. Chemotherapy remains the mainstay of treatment for these patients, despite the disappointing results in the metastatic setting, with response rates ranging from 10% to 30%. These low survival rates call for a rapid introduction of novel drugs targeting recognized molecular alterations, such as those in the PIK3CA/AKT1/PTEN pathway, which is mutated in 35% of TNBC cases.

“The addition of the AKT inhibitor ipatasertib to paclitaxel led to a meaningful improvement of the median overall survival in the first-line treatment of patients with advanced TNBC, according to the findings of the LOTUS trial. The synergism reported in different preclinical studies between inhibitors of PIK3CA/AKT1/PTEN pathway and non-taxane agents claimed for more exhaustive clinical investigations in order to evaluate the toxicity and antitumoral efficacy of the different combinations in this setting” highlighted Dr. Llombart-Cussac, Head of the Medical Oncology Service at the Hospital Arnau de Vilanova, Valencia, Spain and main author of the communication.

Currently 27 patients from multiple sites in Spain and Portugal have already entered the PATHFINDER trial. From MEDSIR, we really hope that this study can help all those taxane-pretreated unresectable locally advanced or metastatic TNBC patients with the introduction of new therapy opportunities.

Check out our ESMO posters, and connect to the available sessions if you want to receive more information:

DEBBRAH - Dr. Marta Vaz-Batista

Abstract: #1537. Presentation Number: 330TiP

Trastuzumab Deruxtecan (DS-8201a) in HER2-Positive and HER2-Low Expressing Metastatic Breast Cancer with Brain Metastases and/or Leptomeningeal Carcinomatosis: DEBBRAH

PATHFINDER – Dr. Antonio Llombart-Cussac

Abstract: #2664; Presentation Number 336TiP

Ipatasertib plus Non-Taxane Chemotherapy for Metastatic Triple-Negative Breast Cancer: PATHFINDER Trial

Contact us if you want to learn more about these or any of MEDSIR’s other exciting clinical trials!



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