SABCS 2021 Highlights & Conclusions
Combination therapy, selective estrogen receptor degraders, and more were covered at the 2021 San Antonio Breast Cancer Symposium.
Immunotherapy May Represent New Standard of Care in Metastatic TNBC
Pembrolizumab (Keytruda) plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) vs chemotherapy alone in patients with previously untreated, locally recurrent, inoperable, or metastatic triple-negative breast cancer (TNBC) with a PD-L1 combined positive score (CPS) of 10 or higher, according to updated data from the phase 3 KEYNOTE-355 trial (NCT02819518).1
Furthermore, a PD-L1 CPS of at least 10 was found to be a reasonable cutoff to define the population of patients expected to derive the most benefit from this regimen. Results showed that the combination of pembrolizumab and chemotherapy yielded a median OS of 23.0 months vs 16.1 months with chemotherapy alone in patients with a CPS of 10 or higher (HR, 0.73; 95% CI, 0.55- 0.95; P = .0093). The 18-month OS rates were 58.3% with pembrolizumab vs 44.7% with placebo or chemotherapy.
Moreover, the median PFS elicited by the combination was 9.7 months vs 5.6 months in patients with a CPS of at least 10 (HR, 0.66; 95% CI, 0.50-0.88). The 12-month PFS rate was 39.1% with pembrolizumab and 23.0% with placebo or chemotherapy.
“These results provide further support for pembrolizumab in combination with chemotherapy as the new standard-of-care treatment regimen for patients with locally recurrent, unresectable, or metastatic TNBC whose tumors express a PD-L1 CPS of 10 or more,” said lead study author Javier Cortés, MD, PhD, head of breast cancer and gynecological cancers at Hospital Universitario Ramón y Cajal in Madrid, Spain, in a presentation of the data.
- Cortes J, Cescon DW, Rugo HS, et al. Final results of KEYNOTE-355: randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Abstract presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX.
Do Oral SERDs Hold Potential to Change Outpatient Practices?
The selective estrogen receptor degrader (SERD) elacestrant (RAD1901) led to a 30% reduction in the risk of disease progression or death compared with standard of care (SOC) in patients with estrogen receptor (ER)–positive, HER2-negative metastatic breast cancer who previously received CDK4/6 inhibition, according to results from the EMERALD trial (NCT03778931).1
Data from the phase 3 trial showed that the median progression-free survival (PFS) by independent review was 2.79 and 1.91 months with elacestrant and standard therapy, respectively, in the intentto-treat population (HR, 0.697; 95% CI, 0.552-0.880; P = .0018). Standard therapy included either fulvestrant (Faslodex) or an aromatase inhibitor.
In a subgroup of patients with ESR1 mutations, elacestrant was linked with a median PFS of 3.78 months vs 1.87 months with standard therapy. This led to a 45% reduction in the risk of disease progression or death in this subgroup (HR, 0.546; 95% CI, 0.387-0.768; P = .0005).
Elacestrant, an oral SERD that blocks ER in a dose-dependent manner, has previously shown clinical activity in postmenopausal women with ER-positive, HER2-negative metastatic breast cancer.2,3 Notably, experts have expressed that continued positive trial outcomes with oral SERDs have the potential to change outpatient practice by eliminating the need for intramuscular fulvestrant injections.4
“Because it is an oral agent, the [main] thing to consider is that it does cause nausea,” stated Aditya Bardia, MD, MPH, Dana-Farber Harvard Cancer Center, in an interview with Oncology Nursing News®. “It can also cause upper GI [gastrointestinal] discomfort. So, those are important education pieces for patients. If a patient is having a lot of acidlike symptoms, then the use of a proton pump inhibitor or other anti-acid [antacid] medications would be very reasonable. If a patient really has severe nausea, then the use of antinausea medication would be reasonable. But overall, the drug is well tolerated.”
- Bardia A. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2-advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: results of EMERALD phase 3 trial. Abstract presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX.
- Bihani T, Patel HK, Arit H, et al. Elacestrant (RAD1901), a selective estrogen receptor degrader (SERD), has antitumor activity in multiple ER+ breast cancer patient–derived xenograft models. Clin Cancer Res. 2017;23(16):4793-4804. doi:10.1158/1078-0432.CCR-16-2561
- Bardia A, Kaklamani V, Wilks S, et al. Phase I study of elacestrant (RAD1901), a novel selective estrogen receptor degrader, in ER-positive, HER2-negative advanced breast cancer. J Clin Oncol. 2021;39(12):1360-1370. doi:10.1200/JCO.20.02272
- Dr Tolaney on the safety profile of SAR439859 in ER+/HER2 metastatic breast cancer. OncLive®. December 10, 2020. Accessed December 22, 2021. https://www.onclive.com/view/dr-tolaney-on-the-safety-profile-of-sar439859-in-er-her2--metastatic-breast-cancer
Breast Cancer–Related Lymphedema Rate Is Higher in Black Women Than White Women
Data presented at the 2021 San Antonio Breast Cancer symposium revealed that in patients with breast cancer treated with axillary lymph node dissection (ALND) and radiotherapy there is a 3.5-fold increased incidence of lymphedema among Black women compared with non-Black women.1
The results also indicated that Hispanic women have a 3-fold increased incidence of breast cancer–related lymphedema compared with White women. However, Andrea V. Barrio, MD, FACS, an associate attending physician in the Breast Service, Department of Surgery at Memorial Sloan Kettering Cancer Center in New York, New York, remarked that more data are needed to confirm this observation.
“Notably, the number of Hispanic women in our study was small,” explained Barrio, lead study author, in a presentation of the data during a press briefing ahead of the conference.
At the beginning of her presentation, Barrio noted that results from epidemiological studies have shown that Black women with breast cancer have an increased susceptibility to developing lymphedema. However, as she discussed, there are very few prospective clinical trial data confirming those results.
“The aim of our study was to assess the incidence of lymphedema in a prospective cohort of patients treated with ALND to identify risk factors associated with lymphedema development and to evaluate the impact of race and ethnicity on lymphedema incidence and severity,” she said.
To evaluate this incidence, Barrio and her colleagues enrolled 827 women age 18 years and older with breast cancer in the trial. Patients also had to have received a unilateral ALND either in the primary setting or after a sentinel lymph node biopsy to be eligible for inclusion in the analysis.
At a median follow-up of 22.6 months, 56 patients had developed lymphedema. The results demonstrated that the 12-month lymphedema rate was 8.8% (95% CI, 5.9%- 13%) and that the 24-month rate was 24.7% (95% CI, 19.2%-31.5%). The highest incidence of lymphedema observed was among Black women, with a 24-month lymphedema rate of 39.4%. That rate was 27.7% in Hispanic women, 23.4% in Asian women, and 20.5% in White women.
The results also showed that receipt of neoadjuvant chemotherapy was associated with a higher 24-month lymphedema rate compared with up-front surgery at 30.9% vs 11.1% (P = .0066). Of note, among women with lymphedema, disease severity did not vary across racial and ethnic groups with similar relative volume changes observed.
“We observed a higher incidence of lymphedema in Black women treated with ALND and radiotherapy after adjustment for other variables. Similar findings were observed in Hispanic women, but confirmation in a larger data set is needed,” Barrio concluded.
- Barrio AV, et al. Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: results of a prospective screening study. Abstract presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX.