By Kate O’Rourke
Data from the RxPONDER trial took center stage at this year’s virtual San Antonio Breast Cancer Symposium (SABCS).
“The hottest thing that was presented this year was the RxPONDER trial looking at women with early-stage estrogen receptor positive breast cancer who have one to three positive lymph nodes and a genomic test done called Oncotype DX,” Dr. Virginia Kaklamani, the Ruth McLean Bowman Bowers Chair in Breast Cancer Research and Treatment and leader of the Breast Oncology Program at Mays Cancer Center in San Antonio, Texas, told OBR.
In this study, 5,015 women with stage 2-3, hormone receptor-positive, HER2-negative breast cancer involving one to three axillary lymph nodes and no distant metastasis whose Oncotype score was between 0 and 25 were randomized to receive endocrine therapy alone or endocrine therapy plus chemotherapy (Abstract GS3-00).
In the premenopausal cohort, those who received chemotherapy had improved 5-year invasive disease-free survival (IDFS), compared with those who did not receive chemotherapy (94.2% vs. 89.0%; P=0.0004), as well as a 53% improvement in overall survival (P=0.032).
“RxPONDER showed that in women who were postmenopausal there was no benefit with chemotherapy, but for women that were premenopausal there was a benefit from chemotherapy,” Dr. Kaklamani said. “This is important because we have had data on Oncotype DX in women with negative lymph nodes, but this is the first large, prospective study that we have had data on in women with positive lymph nodes.”
The study’s current median follow-up is 5.1 years but the RxPONDER trial will follow women for 15 years. It is still unknown why premenopausal women in the study benefited from chemotherapy while postmenopausal women did not. One possible explanation is that chemotherapy can induce menopause, starving the cancer of the hormones it needs to grow, according to the SWOG Cancer Research Network, which designed the study.
Kevin Kalinsky, MD, considers the practice-changing potential of RxPONDER:
The CONTESSA trial also made waves at SABCS. CONTESSA enrolled 685 patients with HER2-negative, hormone receptor-positive metastatic breast cancer (MBC) who had received no more than one chemotherapy regimen for advanced disease and had received a taxane in the neoadjuvant or adjuvant setting (Abstract GS4-01).
In this cohort, the median progression-free survival (PFS) was 9.8 months for tesetaxel with a reduced dose of capecitabine, compared with 6.9 months for capecitabine alone (Hazard Ratio [HR], 0.716; P=0.003). The overall response rate was increased in the tesetaxel arm (57% vs. 41%; P=0.0002), as was the 24-week disease control rate (67% vs. 50%; P <0.0001).
“CONTESSA was a positive study, and it is a registrational trial, which means that the company is going to go to the FDA and seek approval for tesetaxel,” Dr. Kaklamani said. “Assuming they get it, this is going to be one of two taxanes that are oral drugs that we now have data on that may be approved in the near future. Hopefully, this drug will make it to the early-stage setting, so that again, we can use more oral chemotherapy for our patients instead of IV chemotherapy.”
Extended follow-up data from the monarchE trial was also a highlight. The findings showed that the CDK4/6 inhibitor abemaciclib, added to endocrine therapy, improved IDFS in patients with high-risk, node-positive, early-stage, hormone receptor-positive, HER2-negative breast cancer, compared with endocrine therapy alone (Abstract GS1-01).
The 2-year IDFS rate was 92.3% in those who received abemaciclib plus endocrine therapy and 89.3% in those who received endocrine therapy alone.
“This was a relatively premature presentation because we don’t have many years of follow up. I think it’s extremely important to wait for those years of follow up because you don’t know if this difference in metastatic disease is just something that we saw in the first couple of years or whether it is something we are going to continue seeing in 4 or 5 years,” Dr. Kaklamani said. “I think it is still unclear what to do with those results, but it looks very promising.”
Priya Rastogi, MD, considers the interchangeability of CDK 4/6 inhibitors:
This year’s SABCS also included significant discussion about the potential to de-escalate treatment, according to C. Kent Osborne, MD, one of the meeting’s co-directors and founding director of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston, Texas.
Dr. Osborne pointed to the PRIME II trial, which demonstrated that omitting radiation after breast-conserving surgery may not impact 10-year survival rates in women 65 years or older with hormone receptor-positive, early invasive breast cancer (Abstract GS2-03).
The PRIME II investigators recruited 1,326 patients and randomized them to whole breast irradiation or to no whole breast irradiation. The researchers found no difference between the two study cohorts in terms of overall survival or metastasis-free survival.
“They showed that while the in-breast recurrence rate was slightly higher in those patients, above 65 [years old] there was really no difference in overall survival or distant disease-free survival, suggesting that there are some patients above 65 years of age in whom not giving radiation therapy is probably something safe to consider and to talk with patients as an option,” Dr. Osborne told OBR.
Immunotherapy studies also had an important place at the meeting, particularly for patients with triple negative breast cancer (TNBC), Dr. Osborne said. For example, results were presented from the KEYNOTE-355 trial showing that pembrolizumab plus chemotherapy improved the progression-free survival, overall response rate, durable complete remission, and duration of response for patients with locally recurrent, unresectable, or metastatic triple negative breast cancer (TNBC) with tumors expressing PD-L1 and a combined positive score (CPS) of 10 or more (Abstract GS3-01).
The median PFS was 9.7 months in the pembrolizumab arm and 5.6 months in the placebo arm for patients with a PD-L1 CPS of at least 10 (P=0.0012). But among patients with a PD-L1 CPS of at least 1, the median PFS was 7.6 months in the pembrolizumab group and 5.6 months in the placebo group (P=0.0014).
“In patients with metastatic disease, it seems that those tumors that express PD-L1 are those that benefit the most from checkpoint inhibitor therapy, but that doesn’t seem to be the case in early disease. In early disease, patients responded pretty well, even if they were PD-L1 negative,” Dr. Osborne said. “What we need is better biomarkers for response to checkpoint inhibitor immunotherapy in breast cancer. It is clear that PD-L1 is not the end-all biomarker.”
Hope Rugo, MD, offers key takeaways for physicians regarding KEYNOTE-355: