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Clinical Trial Updates from SABCS 2023: Early-Stage Breast Cancer

By BCRF | January 26, 2024

Researchers presented the latest results in early-stage breast cancer research

At this year’s San Antonio Breast Cancer Symposium (SABCS), conference attendees comprised of researchers, students, and patient advocates attended presentations reporting the results of clinical research years in the making. Read on for highlights from those trial updates in early-stage breast cancer—several of which were presented by or involved BCRF investigators.

Adjuvant CDK4/6 inhibition benefits in early-stage hormone receptor-positive/HER2-negative breast cancer

Hormone receptor (HR)–positive, HER2-negative breast cancer accounts for nearly 70 percent of all breast cancer cases in the United States, and many patients diagnosed with stage II and III disease face a high risk of recurrence. Abemaciclib (Verzenio®) and ribociclib (Kisqali®) are part of a class of drugs called CDK4/6 inhibitors; they are small molecule inhibitors targeting CDK4 and CDK6 proteins, which play a critical role in promoting growth of breast cancer cells.  

Dr. Gabriel Hortobagyi, Member Emeritus of BCRF’s Scientific Advisory Board, presented the final analysis from the phase 3 NATALEE trial (NCT03701334[PM1] ) testing the adjuvant (post-surgical) use of ribociclib in women with high-risk HR-positive, HER2-negative early stage (II or III) breast cancer. Participants were randomly assigned to receive either ribociclib for three years with hormonal therapy or hormonal therapy alone for at least five years. The overall survival endpoint data is too immature to present yet; however, the researchers reported significantly extended invasive disease-free survival, consistent across subgroups, with a 25 percent reduction in recurrence in those receiving ribociclib and hormonal therapy.   

The monarchE study (NCT03155997) is a randomized phase 3 trial testing the benefit of adding abemaciclib—another CDK 4/6 inhibitor—to endocrine therapy versus endocrine therapy alone in patients with high-risk HR-positive, HER2-negative early-stage breast cancer. In an interim analysis of overall survival, study investigators found use of abemaciclib led to sustained five-year invasive disease-free and distant relapse-free survival benefit in trial participants.   

Dr. Nicholas Turner of the Royal Marsden Hospital presented a molecular analysis of primary tumors at this year’s meeting, with the goal of associating their genomic profiles with outcomes in monarchE participants. The results supported the use of abemaciclib in HR-positive, HER2-negative high-risk early breast cancer regardless of intrinsic molecular subtypes in both high- and low-risk tumors. 

Biomarker analysis identifies patients likely to benefit from immunotherapy 

The immune system has important proteins in place to keep it from attacking normal, healthy cells. These “checkpoint” proteins can be used by breast cancer cells to avoid being targeted by the immune system. The immunotherapy drugs that target these proteins, PD-1 and PD-L1 in breast cancer, are called immune checkpoint inhibitors (ICIs).

The CheckMate 7FL (NCT04109066) and KEYNOTE-756 (NCT03725059) trials prospectively tested the benefit of anti-PD-1 agents nivolumab (Opdivo®) and pembrolizumab (Keytruda®), respectively. Study investigators previously reported an increase in rates of pathological complete response (pCR)—total disappearance of invasive disease—with the addition of either PD-1 inhibitor to neoadjuvant (pre-surgical) chemotherapy in patients with high-risk, high-grade estrogen receptor (ER)–positive HER2-negative breast cancer.  

In the analysis presented at this year’s meeting, they sought to identify biomarkers that could predict benefit of the therapy in individual patients, as adverse effects of immunotherapies can be significant. In both studies, the benefit was greater in patients with tumors positive for the PD-L1 biomarker (the drugs’ target protein) and lower ER status. 

In CheckMate 7FL, BCRF investigator Dr. Sherene Loi presented that lower progesterone receptor (PR) status and higher amounts of tumor-infiltrating lymphocytes were also identified as biomarkers that predicted a greater benefit of nivolumab. 

The KEYNOTE-522 trial (NCT03036488) tested the earlier use of immune checkpoint inhibition with pembrolizumab plus chemotherapy versus placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo in patients with early-stage triple-negative breast cancer (TNBC). 

At this year’s conference, study investigators presented five-year follow-up data, which captures when most cancer recurrence is observed in patients with TNBC. The data confirmed significant improvements in pathological complete response and five-year event-free survival (81 percent with addition of pembrolizumab to chemotherapy compared to 72 percent with chemotherapy alone).  

Targeted antibody-drug conjugate improves outcomes in HER2-positive early breast cancer

Dr. Sibylle Loibl of Goethe University presented the final invasive disease-free survival and an updated overall survival analysis to the phase 3 KATHERINE trial (NCT01772472) investigating the use of pre-surgical antibody drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1, Kadcyla®) or trastuzumab (Herceptin®) in patients with invasive HER2-positive early breast cancer after neoadjuvant chemotherapy. 

The targeted therapy ado-trastuzumab emtansine (T-DM1/Kadcyla®) was found to significantly improve invasive disease-free survival (80.9 percent compared to 67.1 percent with trastuzumab) and overall survival (89.1 percent compared to 84.4 percent with trastuzumab) in trial participants after seven years of follow up. The first data from this trial was presented five years ago and has already changed the standard of care for patients with residual invasive disease. The updates presented here confirm that patients treated with TDM-1 are experiencing better outcomes.  

Pregnancy after breast cancer 

The POSITIVE study (NCT02308085[MF5] ) is a prospective international, multicenter, single-arm trial of pre-menopausal women with stage I-III HR-positive breast cancer who desired to become pregnant. After completing 18-30 months of adjuvant endocrine therapy, the women were able to take up to a two-year break from therapy to allow for conception after which they would resume endocrine therapy. Researchers found that 74 percent of patients became pregnant after pausing therapy and had similar disease outcomes as patients who didn’t suspend treatment.

In a secondary analysis, investigators focused on patients within POSITIVE who had undergone fertility preservation, such as egg freezing or other assisted reproductive technologies (ART). Dr. Hatem A. Azim, Jr. of the Monterrey Institute of Technology reported that over 82 percent of the patients in the study became pregnant and the use of ART did not increase breast cancer recurrence. Cryopreserved embryo transfer was the most effective ART for pregnancy in this patient population. Younger patients (those under 35) were able to get pregnant in a shorter time. These trial results can give HR-positive breast cancer patients confidence that using fertility preservation and ART will not increase three-year cancer recurrence. While encouraging, longer-term follow-up is warranted.

Dr. Matteo Lambertini of the University of Genova presented data from an international retrospective, hospital-based cohort study (A Multicenter Retrospective Study on the Prognostic Impact of Pregnancy in Women with History of BRCA Mutated Breast Cancer/NCT03673306) looking at cumulative incidence of pregnancy and disease-free survival in young women who are germline BRCA mutation carriers. The results showed that more than one in five BRCA carriers conceived within 10 years after breast cancer diagnosis. Importantly, for most women, pregnancy after breast cancer did not lead to negative impact on the mother’s or baby’s health.

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