Opening General Session features findings from RxPONDER, SOFT, RIGHT Choice trials


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Among the abstracts presented during this year’s opening General Session on Tuesday afternoon, researchers presented findings from studies exploring race and clinical outcomes, the utility of a genomic assay in identifying HR-positive, early-stage breast cancer patients who may benefit from ovarian suppression therapy, and the potential of first-line ribociclib plus endocrine therapy in avoiding or delaying chemotherapy in patients with aggressive HER2-negative breast cancer.

Yara Abdou, MD
Yara Abdou, MD

GS1-01: Race and clinical outcomes in the RxPONDER Trial (SWOG S1007)

Yara Abdou, MD, Assistant Professor of Medicine at the University of North Carolina, Chapel Hill, presented findings demonstrating that non-Hispanic Black women with HR-positive/HER2-negative, lymph node-positive breast cancer had worse outcomes compared to non-Hispanic whites, Asians, and Hispanics, despite similar 21-gene recurrence scores.

Dr. Abdou and her colleagues analyzed the clinical outcomes with respect to race and ethnicity in the RxPONDER clinical trial, which aimed to assess the value of the 21-gene recurrence score (RS) in patients with lymph node-positive, HR-positive/HER2-negative breast cancer and the benefit of adjuvant chemotherapy in these patients.

The researchers found that the 21-gene recurrence scores were similar across all racial subgroups, and there were no significant differences in tumor size and in the number of lymph nodes involved. However, NH Black and Hispanic patients had a higher frequency of high-grade tumors than NH white and Asian patients, Dr. Abdou reported.

According to the RxPONDER trial results, which were initially presented at SABCS in 2020, premenopausal women with HR-positive/HER2-negative breast cancer with one to three positive lymph nodes and RS of 25 or lower benefited from the use of chemotherapy, while postmenopausal women did not.

After 12 months of follow-up, 96% of NH Black patients were still on endocrine therapy compared to 94.8% of NH white patients.

“These data suggest that the differences in long-term outcomes are not likely attributable to lack of treatment compliance among NH Black women within the first year; however, longer follow-up and further analysis is needed to confirm this finding,” Dr. Abdou said.

In accordance with previous studies, she said these results indicate racial disparities in breast cancer, particularly in HR-positive breast cancer.

Maja H. Oktay, MD, PhD
Maja H. Oktay, MD, PhD

GS1-02 Racial disparity in tumor microenvironment and outcomes in residual breast cancer treated with neoadjuvant chemotherapy

In this study, investigators found that residual tumors from Black patients with ER-positive/HER2-negative primary breast cancer treated with neoadjuvant chemotherapy (NAC) had a higher score of a biomarker of distant metastatic recurrence than tumors from white patients, according to Maja H. Oktay, MD, PhD, Professor and Co-leader of the Tumor Microenvironment and Metastasis Program at Montefiore Einstein Cancer Center and Professor of Pathology at Albert Einstein College of Medicine. Dr. Oktay is senior author of the study and presented the findings during an AACR-sponsored press conference prior to the General Session.

Previous research by Dr. Oktay and collaborators led to the identification of three-cell structures in primary breast tumors in which an invasive tumor cell partially inserted into a blood vessel wall is bound to an endothelial cell and a macrophage, and all three are in direct and stable contact.

In this study, Dr. Oktay and her colleagues conducted a retrospective, multi-institutional study of tumor microenvironment of metastasis (TMEM) doorway score and macrophage density in patients with unilateral, invasive breast cancer who received neoadjuvant chemotherapy to determine whether the TMEM doorway score can provide prognostic information about the residual disease after NAC, and whether there were racial differences in the TMEM doorway score in the residual disease.

Their results showed that 49% of Black patients developed distant recurrence, compared to 34.5% of white patients, and that Black women were more likely to receive mastectomy than white women (69.8% and 54%, respectively), and have higher-grade tumors.

Additionally, she reported that tumors from Black patients had more macrophages and a higher TMEM doorway score than tumors from white patients in the entire cohort and in the ER-positive/HER2-negative subset, but not in the triple-negative subset.

“Our study provides a potential explanation for the persistent racial disparities in ER-positive/HER2-negative breast cancer outcomes that are not fully explained by disparities in social determinants of health, including access to care or treatment,” said Dr. Oktay.

Ruth O’Regan, MD
Ruth O’Regan, MD

GS1-06 Evaluation of the Breast Cancer Index in premenopausal women with early-stage HR+ breast cancer in the SOFT trial

Ruth O’Regan, MD, Charles A. Dewey Professor & Chair of Medicine at the University of Rochester Medical Center in New York, reported results showing that, among premenopausal women with HR-positive, early-stage breast cancer enrolled in the Suppression of Ovarian Function Trial (SOFT) trial, those with a high score on Breast Cancer Index (BCI) genomic assay had increased risk of distant recurrence, and those with low BCI benefited more from the addition of ovarian suppression therapy to endocrine therapy after 12 years of follow-up.

“The SOFT trial showed that adding ovarian function suppression (OFS) to endocrine therapy benefited a subset of premenopausal women with HR-positive, early-stage breast cancer. However, OFS increases short and long-term toxicity and is not tolerated by all patients,” Dr. O’Regan said. “Therefore, determining which patients truly need OFS is crucial to avoid added toxicities in patients who are unlikely to benefit.”

Dr. O’Regan and colleagues evaluated BCI in a subset of 1,687 patients enrolled in the SOFT trial to determine whether BCI can predict prognosis and benefit from OFS in premenopausal women with HR-positive, early-stage breast cancer who received endocrine therapy with or without chemotherapy.

The analysis showed that, after 12 years of follow-up, BCI was prognostic of distant recurrence: Among patients without lymph node involvement, those with high BCI had a 98% increased risk of distant recurrence than those with low BCI. A similar increase was observed in patients whose cancer had spread to one to three lymph nodes.

Yen-Shen Lu, MD, PhD
Yen-Shen Lu, MD, PhD

GS1-10 Primary results from the randomized Phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2− advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy

In patients with HR-positive, HER2-negative, advanced breast cancer — including patients with visceral crises — those treated with ribociclib plus endocrine therapy had fewer adverse events and a significantly longer progression-free survival compared to those treated with combination chemotherapy, according to results from the phase II RIGHT Choice trial, reported on Tuesday at SABCS by Yen-Shen Lu, MD, PhD, Professor at National Taiwan University Hospital.

“These findings suggest that, through the use of first-line ribociclib plus endocrine therapy, we may be able to avoid or delay chemotherapy and spare patients — even those with aggressive, life-threatening disease — the toxicities and discontinuations associated with chemotherapy,” Dr. Lu said.

Dr. Lu and colleagues designed the phase II RIGHT Choice clinical trial to compare the outcomes of patients with aggressive disease treated with ribociclib plus endocrine therapy to those treated with combination chemotherapy.

Among their findings, Dr. Lu reported that patients treated with ribociclib plus endocrine therapy had a progression-free survival of 24 months, nearly one year more than that of patients treated with chemotherapy (12.3 months). The median time to treatment failure was also longer among patients treated with ribociclib plus endocrine therapy—18.6 months versus 8.5 months among patients treated with chemotherapy.

The overall response rate was similar between the two treatment arms; however, the rates of symptomatic adverse events, such as diarrhea and fatigue, were different. Serious, treatment-related adverse events emerged in 1.8% of patients receiving ribociclib plus endocrine therapy and in 8% of patients receiving combination chemotherapy. Similarly, 7.1% of patients treated with ribociclib plus endocrine therapy and 23% of patients treated with chemotherapy discontinued at least one component of study treatment due to treatment-related adverse events.

“Compared with combination chemotherapy, ribociclib plus endocrine therapy may offer more durable antitumor efficacy with better tolerability and compliance,” Dr. Lu said. “Overall, these improvements in outcomes and tolerability should translate into an evolution of our standard of care for patients with hard-to-treat breast cancer, providing clinicians with guidance for treating this patient population.”

On-Demand Session Availability

Daily sessions will be available for on-demand viewing 3-5 days following the 2022 Symposium (author permitting). They will be available exclusively to registered SABCS attendees until March 2023. Following March 2023, they will be available on under the “Resources” tab.