More women with early-stage breast cancer may safely forgo chemotherapy, suggests an interim analysis of the large-scale phase 3 RxPONDER trial, presented at the San Antonio Breast Cancer Symposium 2020.
The investigators reported that adding chemotherapy to endocrine therapy did not improve outcomes for postmenopausal women with low-risk, node-positive, hormone receptor–positive (HR+), HER2-negative (HER2–) breast cancer in comparison with endocrine therapy alone.
These results are akin to those from the TAILORx trial. The results of that trial were first presented in 2018 and have changed practice for women with early-stage disease who have no lymph node involvement.
Clinicians celebrated the new results for women with lymph node–positive disease.
“RxPonder: practice changing!!!” tweeted meeting attendee Sarah Sammons, MD, Duke Cancer Center, Durham, N.C.
“Data from RxPonder are the most clinically important this year at @SABCSSanAntonio,” tweeted Hal Burstein, MD, Dana Farber Cancer Institute, Boston, who was not involved in the study.
“This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions,” asserted study lead author Kevin Kalinsky, MD, Winship Cancer Institute of Emory University, Atlanta, during a meeting press conference.
But the trial, run by the SWOG Cancer Research Network, was not without controversy.
That’s because the trial also included premenopausal women whose disease characteristics were the same and who were found to have benefited from chemotherapy.
It was not clear whether the benefit was from chemotherapy’s cytotoxicity or its endocrine effects/ovarian suppression (which limits the production of estrogen, a breast cell stimulant) in these young women. But multiple experts asserted that the effect was very likely from ovarian suppression.
“There are less toxic ways than chemo to suppress ovarian function,” tweeted Tatiana Prowell, MD, Johns Hopkins University, Baltimore, who is not a study investigator.
Some experts strongly doubted the findings in premenopausal women.
“I hate to come away with the message that all [low-risk, node-positive] premenopausal patients should get chemotherapy,” summarized C. Kent Osborne, MD, Baylor College of Medicine, Houston, who is codirector of SABCS and was not involved in the study.
RxPONDER will follow patients for 15 years, so additional data and insights will follow, observed SWOG in a press statement.
Women had limited positive nodes
RxPONDER, or SWOG S1007, involved more than 5000 women who had HR+, HER2– breast cancer with involvement of one to three lymph nodes. The patients’ recurrence score was ≤25 on a 21-tumor gene expression assay (Oncotype Dx), which is characterized as low risk.
Approximately 20% of U.S. women with nonmetastatic HR+, HER2– breast cancer present with involvement of one to three lymph nodes, Dr. Kalinsky noted.
Study participants were randomly assigned to receive either standard chemotherapy plus endocrine therapy or endocrine therapy alone. Follow-up was for a median of 5 years before the current preplanned analysis.
Over a median follow-up of 5.1 years, there were 447 observed invasive disease-free survival (IDFS) events, the primary endpoint, which is 54% of the expected number at final analysis.
Across the whole cohort, adding chemotherapy to endocrine therapy was associated with a significant improvement in IDFS, with a 5-year rate of 92.4% vs 91.0% for endocrine therapy (P = .026).
Among the postmenopausal women, no such improvement was seen. The 5-year IDFS rate was 91.6% with chemotherapy plus endocrine therapy and 91.9% with endocrine therapy alone (P = .82).
Among premenopausal women, there was improvement in IDFS. The 5-year rate was 94.2% with chemotherapy plus endocrine therapy and 89.0% for endocrine therapy alone (P = .0004).
These differences were reflected in the results for overall survival. For postmenopausal women, there was a nonsignificant difference in 5-year overall survival rates (96.2% vs. 96.1%).
On the other hand, for premenopausal women, there was a significant difference in 5-year overall survival rates (98.6% vs. 97.3%; P = .032).
Stratifying patients by recurrence score, 0-13 versus 14-25, and by involvement of one versus two to three nodes did not have a major impact on the results, said Dr. Kalinsky, who also noted that future analyses will include quality of life and other outcomes.