SWOG-S2212 –  A Randomized Phase III Study of Shorter Anthracycline-Free Chemo Immunotherapy Adapted to Pathological Response in Early Triple Negative Breast Cancer (SCARLET)

Description: This phase III trial compares the effects of shorter chemotherapy (chemo)-immunotherapy without anthracyclines to usual chemo-immunotherapy for the treatment of early-stage triple negative breast cancer. Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body’s immune response. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Doxorubicin is an anthracycline chemotherapy drug that damages DNA and may kill cancer cells. Pembrolizumab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Shorter treatment without anthracycline chemotherapy may work the same as the usual anthracycline chemotherapy treatment for early-stage triple negative breast cancer.

ClinicalTrials.gov ID NCT05929768

Alliance-a012103 - de-escalation of therapy in early-stage tnbc patients who achieve pcr after neoadjuvant chemotherapy with checkpoint inhibitor therapy

Description:   The phase III trial compares the effect of pembrolizumab to observation for the treatment of patients with early-stage triple-negative breast cancer who achieved a pathologic complete response after preoperative chemotherapy in combination with pembrolizumab. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help researchers determine if observation will result in the same risk of cancer coming back as pembrolizumab after surgery in triple-negative breast cancer patients who achieve pathologic complete response after preoperative chemotherapy with pembrolizumab.

Clinicaltrials.gov/study/NCT05812807

NRG-BR007 - A phase III clinical trial evaluation de-escalation of breast radiation for conservative treatment of stage i, hormone sensitive, her2-negative, oncotype recurrence score less than or equal to 18 breast cancer (debra)

Description:   This Phase III Trial evaluates whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.

Breast conservation therapy for early stage breast cancer has been an important achievement of oncology practice in the last half century and breast radiotherapy (RT) has been essential in its development. Several seminal randomized clinical trials conducted in the 1980's era demonstrated that breast radiotherapy following lumpectomy yielded overall survival outcomes equivalent to mastectomy for treatment of early stage invasive breast cancer leading to the National Institute of Health (NIH) Consensus Conference statement in 1991 supporting breast conservation treatment.This established lumpectomy with RT as an alternative to mastectomy and subsequently the rate of breast conservation for eligible breast cancer patients rose steadily. Shortly thereafter, investigators recognized that the toxicity, patient burden, and geographic barriers associated with the protracted treatment course for breast RT was a potential barrier to breast conservation utilization. Numerous phase III clinical trials were conducted randomizing women post lumpectomy to RT vs. observation aimed at identifying which cases did not derive a significant RT benefit. No such subsets of breast cancer patients were consistently identified, thereby solidifying the standard that breast conservation required both lumpectomy and RT. Two meta-analyses by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) in 2005 and 2011 further reinforced the value of breast RT post lumpectomy by examining the relationship of local recurrence and breast cancer mortality relative to the use of breast RT post lumpectomy. In each analysis, it found for axillary node negative breast cancer patients undergoing breast conservation a small but consistent increase in breast cancer mortality when breast radiotherapy was omitted. As a result, breast RT after lumpectomy has become an established paradigm for breast conservation for early stage breast cancer and is recommended by the NCCN 2018 guidelines (as it has for nearly two decades) that are commonly used today by clinicians and health systems alike. The landscape of early stage breast cancer has changed dramatically over the past three decades since the establishment of breast conservation. Widespread screening with mammography has led to the diagnosis of smaller and earlier stage disease. All breast cancers are now routinely characterized by their hormone sensitivity based on the presence of estrogen and progesterone receptors on tumor cells within the biopsy or surgical specimen and presence of HER2 (human epidermal growth factor receptor 2) which has provided an additional means of stratifying breast cancer into distinct prognostic groups. Small, node negative invasive breast cancer that is hormone sensitive (HS) and HER2-negative has a lower overall recurrence rate (local, regional, and distant) than breast cancers characterized by more adverse clinical pathologic features. However, other than in a smaller subset of women greater than 70 years old, clinical trials in this HS population still demonstrated unacceptable local recurrence risks long term after lumpectomy alone emphasizing that clinical and pathologic features are insufficient for consistently identifying when RT can safely be omitted.

Clinicaltrials.gov/study/NCT04852887