Studies presented at ESMO Congress 2022 may help inform the treatment of breast cancer, suggesting new treatment options, confirming current practices, and raising questions about optimal care.
For example, overall survival (OS) results from the phase 3 TROPiCS-02 trial support the use of sacituzumab govitecan over chemotherapy in patients with endocrine-resistant, hormone receptor (HR)-positive, HER2-negative, advanced breast cancer.1
Long-term results from the phase 3 GIM2 trial support a chemotherapy dosing schedule of every 2 weeks, rather than every 3 weeks, in patients with node-positive, early breast cancer, regardless of HR status.2
Final results from the phase 3 DATA trial suggest that extending aromatase inhibitor (AI) treatment beyond 5 years of sequential therapy is only beneficial for certain postmenopausal patients with HR-positive breast cancer.3
And results from the phase 2 METEORA-II trial suggest an all-oral metronomic chemotherapy regimen can provide efficacy gains — but more toxicity — when compared with single-agent paclitaxel as first- or second-line therapy in patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer.4
TROPiCS-02 Trial: Sacituzumab Govitecan Improves OS
The phase 3 TROPiCS-02 trial suggests that sacituzumab govitecan can significantly improve OS, compared with physician’s choice of chemotherapy, in patients with endocrine-resistant, HR-positive, HER2-negative, advanced breast cancer.1
The trial (ClinicalTrials.gov Identifier: NCT03901339) enrolled patients who had received at least 1 taxane, endocrine therapy, and CDK4/6 inhibitor in any setting, as well as 2-4 chemotherapy regimens in the metastatic setting.
The patients were randomly assigned to receive sacituzumab govitecan (n=272) or physician’s choice of treatment (n=271) until disease progression or unacceptable toxicity. The physician’s choice treatment options were capecitabine, vinorelbine, gemcitabine, or eribulin.
Previous results from this trial showed a 34% reduction in the risk of progression or death with sacituzumab govitecan (hazard ratio, 0.66; 95% CI, 0.53-0.83; P =.0003).5
In the current analysis, with a median follow-up of 12.5 months, OS was significantly improved with sacituzumab govitecan.1 The median OS was 14.4 months with the antibody-drug conjugate and 11.2 months with physician’s choice of chemotherapy (hazard ratio, 0.79; 95% CI, 0.65-0.96; P =.020). The 12-month OS rate was 61% and 47%, respectively.
“The statistically significant and clinically meaningful benefit of sacituzumab over TPC [treatment of physician’s choice] in the TROPiCS-02 study supports the use of sacituzumab as a novel therapy for patients with pretreated, endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer,” said study presenter Hope S. Rugo, MD, of the University of California, San Francisco.
“The results, in my opinion, are clinically meaningful and should lead to regulatory approval,” said study discussant Meritxell Bellet Ezquerra, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain.
Dr Bellet Ezquerra pointed out that TROPICS-02 is the largest late-line trial specifically conducted in ER-positive, HER2-negative metastatic breast cancer and addresses an unmet medical need.
However, she drew attention to the fact that screening failures occurred in 30% of patients, which means the results may not apply to at least one-third of patients with metastatic breast cancer in this advanced setting.
GIM2 Trial: Dose-Dense Chemo Improves DFS, OS
End-of-study results from the phase 3 GIM2 trial suggest that dose-dense chemotherapy can improve both disease-free survival (DFS) and OS in patients with node-positive, early breast cancer, regardless of HR status.2
This study (ClinicalTrials.gov Identifier: NCT00433420) included 2091 randomized patients. The study was designed to compare dose-dense chemotherapy (given every 2 weeks) and standard-interval chemotherapy (given every 3 weeks) as well as to compare combination epirubicin, cyclophosphamide, and paclitaxel (ECP) with fluorouracil plus ECP (F-ECP).
There were 502 patients who received dose-dense ECP, 500 who received dose-dense F-ECP, 545 who received standard-interval ECP, and 544 who received standard-interval F-ECP.
In a prior analysis, with a median follow-up of 7 years, dose-dense chemotherapy improved DFS, but there was no benefit observed with F-ECP over ECP.6
In the current analysis, the median follow-up was 15.2 years.2 The 15-year DFS rate was similar between the ECP and F-ECP arms — 59% and 55%, respectively (hazard ratio, 1.12; 95% CI, 0.98-1.29; P =.1092). The 15-year OS rate was similar between these arms as well — 74% and 72%, respectively (hazard ratio, 1.13; 95% CI, 0.94-1.36; P =.1811).
In contrast, dose-dense chemotherapy significantly improved both DFS and OS. The 15-year DFS rate was 61% in the dose-dense arm and 52% in the standard arm (hazard ratio, 0.77; 95% CI, 0.67-0.89; P =.0004). The 15-year OS rate was 76% and 69%, respectively (hazard ratio, 0.72; 95% CI, 0.60-0.86; P =.0004).
The benefits with dose-dense chemotherapy were observed in patients with HR-positive or HR-negative tumors, said study presenter Lucia Del Mastro, MD, of IRCCS Ospedale Policlinico San Martino in Genoa, Italy.
Based on these results, Dr Del Mastro concluded that dose-dense chemotherapy should be considered among the optimal regimens for node-positive breast cancer patients who are candidates for adjuvant chemotherapy, irrespective of HR status.
“This is an important trial,” said study discussant Peter Dubsky, MD, PhD, of Breast Centre Klinik St. Anna in Lucerne, Switzerland.
The results confirm that moderate efficacy gains from chemotherapy can translate to clinically relevant gains in OS, irrespective of biomarkers, he explained.