The primary end point of the study was IDFS and a secondary end point was DRFS. The previously reported results showed differences in IDFS and DRFS between premenopausal and postmenopausal patients who received chemotherapy. At a median follow-up of 6.1 years, the updated results contained 553 IDFS events. The results showed that in patients who were premenopausal, there was a 5-year absolute benefit of 4.9% for IDFS with chemotherapy (adjusted HR, 0.64; 95% CI, 0.47-0.87; 2-sided P = .004). There was a 5-year absolute benefit of 2.5% for DRFS with chemotherapy (adjusted HR, 0.66; 95% CI, 0.45-0.97; 2-sided P = .033).
“In an updated analysis, we report with longer follow-up that postmenopausal women with recurrence scores of 0 to 25 continue to not benefit from adjuvant chemotherapy,” said Kalinsky. In postmenopausal women, the 5-year IDFS rate was 91.2% in those treated with chemotherapy plus endocrine therapy compared with 91.9% in those treated with endocrine therapy alone (adjusted HR, 1.06; 95% CI, 0.87-1.30; 2-sided P = .55). The 5-year DRFS rate was 94.3% with added chemotherapy vs 94.8% without (adjusted HR, 1.12; 95% CI, 0.88-1.44; 2-sided P = .35).
“However, premenopausal women with recurrence scores 0 to 25 do, with a 44% to 46% decrease in IDFS, DRFS, and DRFI events,” Kalinsky added.
For premenopausal patients, those who received chemotherapy demonstrated an improved DRFI of 2.4% (adjusted HR, 0.64; 95% CI, 0.43-0.95; 2-sided P = .026) over those who only received endocrine therapy. For those with an RS of 0 to 13, the DRFI was 2.3%, while it was 2.8% for those with an RS of 14 to 25. However, postmenopausal patients did not show any DRFI benefit from chemotherapy in addition to endocrine therapy (HR, 1.12; 95% CI, 0.82-1.52; 2-sided P = .49).
Post hoc analysis showed that in 206 premenopausal women who had micrometastases of 0.2 to 2 mm in their lymph nodes, a 7.3% absolute benefit in IDFS from chemotherapy was observed with a hazard ratio of 0.44 (95% CI, 0.18-1.08). The absolute benefit in 5-year IDFS for 1403 patients with larger lymph node metastases of over 2 mm was 4.8% (HR, 0.64; 95% CI, 0.46-0.90).
“It does appear that premenopausal women with [only] micrometastases benefit from chemotherapy, though there [was] a limited number of events [n = 22], and there was a wide confidence interval,” Kalinsky noted.
In premenopausal patients who only received endocrine therapy, 50% stopped having periods in the first 6 months, compared with 25% of those who received chemotherapy as well. In the first 24 months, 58.9% of those receiving only endocrine therapy stopped having periods within the first 24 months, while 80.8% of those who also received chemotherapy stopped having periods in the first 24 months. In both arms, patients who stopped having periods also had a higher IDFS rate vs those who continued to have periods, with a hazard ratio of 1.56 (95% CI, 0.85-2.86) in those receiving chemotherapy and endocrine therapy vs a hazard ratio of 1.48 (95% CI, 0.92-2.40) in those receiving only endocrine therapy.
For those only treated with endocrine therapy, a 2-year landmarked analysis of ovarian function suppression (OFS) was meant to determine if it was linked to IDFS. A total 17.2% of premenopausal patients in this group underwent OFS. However, no difference in IDFS was observed based on OFS status (HR, 0.88; 95% CI, 0.47-1.63). The study was not able to establish that the benefit from chemotherapy was related to OFS. OFS rates were low in both treatment arms but were higher in the endocrine therapy–alone arm.
“It remains unclear if ovarian function suppression can replace chemotherapy in premenopausal women with hormone receptor–positive, HER2-negative, node-positive breast cancer,” Kalinsky said. “We conclude that future randomized trials should be considered to address this important clinical question in a genomically-defined population.”
Kalinsky K. Updated results from a phase 3 randomized clinical trial in participants (pts) with 1-3 positive lymph nodes (LN), hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25 randomized to endocrine therapy (ET) +/- chemotherapy (CT): SWOG S1007 (RxPONDER). Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS2-07.