Definitive results from the RxPONDER trial have far-reaching implications for women with early-stage HR-positive, HER2-negative breast cancer

A groundbreaking, BCRF-supported phase III clinical trial, RxPONDER, has just demonstrated that some women with a common type of breast cancer can forgo chemotherapy and be successfully treated with hormone therapy alone.

Investigators from the RxPONDER study found no added benefit of chemotherapy in postmenopausal women with hormone receptor (HR)-positive, HER2-negative primary breast cancer that has spread to three or fewer lymph nodes if they have low to moderate risk of recurrence as measured by the Oncotype DX® genomic test. The study also demonstrated the opposite was true for premenopausal women: They benefitted from chemotherapy.

Kevin Kalinsky, MD, MS, a SWOG Cancer Research Network investigator from Emory University, will present the results tomorrow at the 2020 virtual San Antonio Breast Cancer Symposium.

RELATED: Read More of BCRF's SABCS 2020 Coverage

Novel results with wide applicability

The results of this study could improve the care of tens of thousands of women each year. In the U.S., half of all breast cancers are HR-positive and HER2-negative, and the median age of a diagnosis is 62—years after the average woman has finished menopause.

“Chemotherapy is a lifesaving treatment for millions. But as many people who have undergone this treatment can attest, it is arduous. The RxPONDER study is a huge step forward in ensuring that the right patients are receiving the right treatment—and the right amount of treatment,” said BCRF Scientific Director Dr. Judy Garber. “The impact of this study will be felt immediately—sparing thousands the difficult short- and long-term side effects of chemotherapy, while assuring other patients undergoing chemo that they are receiving necessary, effective treatment.”

Building on prior innovative results

Chemotherapy, coupled with anti-estrogen hormone therapy, has been a standard of care for node-positive (meaning the cancer has spread to the lymph nodes), hormone-sensitive breast cancer for more than three decades and has saved the lives of many women. But today, we now know that not all of these patients need this treatment for a good prognosis.

The clinical and research communities have eagerly awaited results from RxPONDER (S1007since the BCRF-supported TAILORx trial demonstrated that most women with early-stage estrogen receptor (ER)-positive, HER2-negative breast cancer that had not spread to the lymph nodes could safely forego chemotherapy and be effectively treated with hormone therapy alone. RxPONDER extended TAILORx’s findings to include patients who are often considered to be at a higher risk of recurrence: those whose breast cancer has spread to one to three lymph nodes.

Both studies used a prognostic test called Oncotype Dx® that determines a patient’s risk of disease recurrence by measuring levels of 21 genes in the tumor. The test assigns a Recurrence Score from one to 100, with one to 10 indicating a low risk of recurrence, 11-25 indicating intermediate risk, and 26-100 indicating high risk.

RELATED: BCRF-Supported TAILORx Study Shows Many Women with Early Stage Breast Cancer Can Avoid Chemotherapy

Overwhelming evidence supported an early release of findings

The RxPONDER study screened 9,383 women with HR-positive, HER2-negative breast cancer that had spread to between one and three lymph nodes. All had low to intermediate risk of recurrence based on Oncotype Dx® testing (Recurrence Scores of 25 or less). Of those, 5,083 women—two-thirds of whom were postmenopausal—were randomly assigned to receive hormone therapy alone or hormone therapy plus chemotherapy (including a taxane and/or an anthracycline). Data from 5,015 patients were included in the analysis.

After a median follow-up of five years the results were impressive: Nearly 92 percent of postmenopausal women in both groups remained disease-free, meaning postmenopausal women saw no added benefit from chemotherapy regardless of their Recurrence Score.

“RxPONDER showed that by using the 21-gene Recurrence Score, we can identify a large group of postmenopausal women with breast cancer who have low rates of recurrence and receive no additional benefit from chemotherapy when added to endocrine therapy, even though the cancer has already spread to the lymph nodes,” said BCRF investigator Dr. Julie R. Gralow. “These women can safely be spared the toxicities of chemotherapy without impacting their risk of recurrence or survival. This is a tremendous advancement.”

Because these results were so clear and important, the study’s independent data and safety monitoring committee recommended that they be reported to the public early, and the National Cancer Institute agreed.

Of equal importance was the finding that premenopausal patients benefitted from chemotherapy, even with low to moderate Recurrence Scores. In this group, 89 percent of patients receiving only hormone therapy remained disease-free after five years, compared to 94 percent for those who received chemotherapy with hormone therapy. Read more here.

“Whether this benefit was due to the chemotherapy itself, or the chemotherapy’s side effects of ovarian suppression and premature menopause, cannot be determined from this study,” Dr. Gralow noted. “This is a critically important question for our premenopausal patients that needs to be addressed in additional studies.”

What’s to come from RxPONDER

While these results are reported after five years of study, RxPONDER is going to follow these patients for many years, yielding more evidence and greater clarity as time goes on.

Both TAILORx and now RxPONDER are certain to influence clinical practice. Their findings arm patients and doctors with critical information to make more informed decisions about optimizing treatment. 

BCRF’s critical financial support of the TAILORx and RxPONDER trials span 15 and 10 years, respectively. For RxPONDER alone, the Foundation provided more than $3 million between 2010 and 2015 for Oncotype DX® testing and $300,000 in 2019 for additional blood-based testing to identify patients at risk of recurrence.

“TAILORx and RxPONDER are remarkable studies for many reasons, in addition to their indicating the right therapy for an individual patient,” said BCRF’s Founding Scientific Director Dr. Larry Norton. “They show the value of large, simple trials that are based on creative, sound science to inform clinical practice. Moreover, they demonstrate that government, industry, academia, and philanthropy, working together, can achieve important advances. Commitment, cooperation, and collaboration are core principles of BCRF, and we are proud to have supported these clinical trials.”

Members of the press can contact BCRF at press@bcrf.org

Watch an interview with BCRF investigator Dr. Julie R. Gralow on RxPONDER below

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