DECRESCENDO (BIG 19-02)

Intro text: 

De-Escalation of adjuvant ChemotheRapy in HER2-positive, EStrogen reCEptor-negative, Node-negative early breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy and Dual HER2 blOckade

DECRESCENDO aims to test a less-intensive chemotherapy regimen (containing 1 drug instead of 3 to 4 drugs) given in combination with the standard HER2 blockade therapy prior to surgery (neoadjuvant) for patients with HER2-positive, hormone receptor-negative breast cancer, as an attempt to reduce the frequency of adverse events without compromising treatment’s efficacy. After surgery, patients with a pathological complete response (pCR) will receive HER2 blockade therapy without chemotherapy. Patients with residual disease will receive standard of care chemotherapy.

In a sub-study of the main trial called the ‘flexible care sub-study, after surgery, patients will receive part of their treatment at home.

The standard treatment for patients with HER2-positive breast cancer is based on surgery to remove the tumour. In order to improve the effectiveness of surgery, chemotherapy (consisting of a combination of 3 to 4 drugs), combined with HER2 blockade therapy either before or after surgery, is recommended. With this type of standard treatment, more than 90% of the patients remain alive and free of cancer recurrence after five years2.

Although these rates are encouraging, there is still room for improvement. Recent studies have shown promising results in patients treated after surgery with HER2 blockade alone and no chemotherapy.

Furthermore, the combination of chemotherapy and HER2 blockade can cause adverse side effects such as hair loss, nausea, vomiting, fatigue, anemia, increased risk of infections, cardiac failure, and leukemia. Most of these side effects can be attributed to chemotherapy, rather than to HER2 blockade.  

As an attempt to reduce these side effects, the DECRESCENDO study aims to test a new treatment regimen that relies on the administration of only 1 chemotherapy drug (rather than the conventional 2 to 4 drugs) associated with the HER2 blockade prior to surgery. The goal of this study is to show that this new treatment regimen is as effective as the conventional one, but with less potential to cause side effects.

2. Patel A, Unni N and Peng Y. The Changing Paradigm for the Treatment of HER2-Positive Breast Cancer. Cancers (Basel). 2020 Aug; 12(8): 2081.

DECRESCENDO is a large multicenter phase 2 study.

All patients will receive the same treatment before surgery (HER2 blockade with one chemotherapy drug, either paclitaxel or docetaxel). Depending on the patients’ tumour status observed at surgery (pathological complete response or residual disease), they will receive different treatments after surgery.

Patients will be treated for 13 months (up to 16 months for those patients who will receive additional chemotherapy after surgery). Once the treatment period has finished, patients will be subject to follow-up and the total duration of the study is estimated to be five years, including treatment and follow-up.

Furthermore, in this study a subcutaneous administration of the HER2 blockade will be used as an alternative to the conventional intravenous administration of the HER2 blockade. Indeed, the subcutaneous route has proven to be as safe and effective as intravenous administration and significantly reduce the time spent by the patients in the hospital at each treatment session.

The sub-study will be conducted in 121 patients to look at patient preference and satisfaction with receiving adjuvant treatment at home or in the hospital.

The study is open to patients with HER2-positive breast cancer whose tumours present certain other characteristics (the absence of hormonal receptors, tumour size between 1.5 cm and 5 cm and no lymph nodes compromised by the tumour).

A total of 1,065 patients from approximately 164 hospitals worldwide are expected to be enrolled in this study.

This is a BIG co-lead study that is being conducted and sponsored by the Institut Jules Bordet – Clinical Trials Support Unit (IJB/CTSU), in collaboration with the Breast International Group (BIG).

Recruitment opened in 2022 and is ongoing.

Approximately 164 hospitals worldwide are participating.

Not at present

DECRESCENDO is made possible by a research grant and drugs provided by Roche. The study is an investigator-initiated study that is being run according to BIG’s Principles of Research Conduct.

ClinicalTrials.gov identifier: NCT04675827