Breast cancer is the most common gynecological tumor, and the endless emergence of new anti-cancer drugs has brought a wider range of treatment options to patients. From early phase 1/2 to critical phase 3 data, the 2021 San Antonio Breast Cancer Symposium (SABCS) is full of exciting research, including selective estrogen receptor degraders (SERDS), CDK4/6 inhibitors, and antibody-coupled drugs (ADCs).
Selective estrogen receptor degrader SERD
At the meeting, updated data from the second group of the ongoing Phase 1/2 AMEERA-1 trial were presented. This study enrolled postmenopausal women with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer who had previously received at least 6 months of advanced endocrine therapy, or who had relapsed within two years prior to treatment or 12 months after completion of adjuvant endocrine therapy. Patients received 200 mg of the selective estrogen receptor degrader amcenestrant once daily, plus 125 mg of palbociclib (Ibrance), in a 28-day cycle of 21 days. In the respondable population, the median follow-up was 48.3 weeks, and the objective response rate (ORR) was 32.4% (n=11/34; all were partial responses). The 24-week clinical benefit rate (CBR) was 73.5% (n = 25/34).
In terms of safety, adverse reactions (TRAEs) related to the use of amcenestrant and palbociclib at all levels occurred in 69.2% (n= 27/39) and 89.7% (n= 35/39) of patients, respectively; TRAEs at level 3 or above occurred in 12.8% (n= 27/39) and 89.7% (n= 35/39) of patients, respectively. 5/39) and 46.2% (n =18/39) of patients. The combination continues to exhibit encouraging activity, sustained clinical benefits, and generally favorable safety characteristics. The combination of the new oral SERDs and CDK4/6 inhibitors will be more effective than the use of SERDs as a single drug.
CDK4/6 inhibitors
The Triniti-1 trial evaluated the disease progress of Ribociclib (Kisqali), everolimus (Afinitor), and Exemetan after the use of CDK4/6 inhibitors in postmenopausal patients with intracranial refractory, hormone receptor-positive, and HER2-negative advanced breast cancer. In this study, patients received 25 mg of oral exemetan once a day, while taking 300 mg of Ribociclib and 2.5 mg of everolimus (the first group) or 200 mg of Ribociclib and 5 mg of everolimus (the second group).
The results showed that the ORR was 6.5% in group 1 and 9.4% in group 2; the 24-week CBR was 65.2% and 59.4% in groups 1 and 2, respectively. The median PFS was 8.0 months (95% CI, 3.8–14.5) in group 1 and 4.7 months (95% CI, 2.0–12.7) in group 2 (HR, 0.740; 95% CI, 0.424–1.291). The median OS was 27.4 months in group 1 and could not be estimated in group 2.
The most common all-grade adverse events were stomatitis (54.3%), infection (50.0%), neutropenia (43.5%), and fatigue (43.5%) in group 1, and infection (48.5%), nausea (42.4%), stomatitis (36.4%), and cytopenia (36.4%) in group 2.
Previous pooled analyses of patients in the MONALEESA trial showed that ribociclib plus endocrine therapy, compared with placebo plus endocrine therapy, had a significant PFS benefit in cohort A (HR, 0.63; P<0.0001), cohort B (HR, 0.52; P<0.0001), and HER2 enriched (HR, 0.39; P<0.0001) subtypes.
In an updated analysis of the phase 3 MONALEESA trial, researchers evaluated overall survival (OS) in patients with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib plus endocrine therapy. The OS analysis showed consistent OS benefits in cohort A (HR, 0.75; P = .021), cohort B (HR, 0.69; P = .023), and the HER2-enriched subtype (HR, 0.60; P = .018). This further confirms the prognostic value of ribociclib plus endocrine therapy compared to endocrine therapy alone for patient OS.
Antibody-coupled drug ADC
Phase 1 TROPION-PanTumor01 enrolled patients with relapsed/refractory advanced or metastatic solid tumors. The cohort results announced at SABCS in 2021 include patients with triple-negative breast cancer. The dose of the new ADC drug datopotamab deruxtecan is 8mg/kg (n=2) and 6mg/kg (n=2). 42).
The results reflected an ORR of 34% (n = 15), including a confirmed complete response (CR) rate of 32% (n = 14). In patients who had not previously received an ADC based on a topoisomerase I inhibitor, the ORR was 52% (n = 14), and the CR rate was 48% (n = 13). The most common adverse events were nausea and stomatitis, mostly grade 2 or lower. Furthermore, hematologic toxicity and diarrhea occurred infrequently, and no cases of drug-related interstitial lung disease were observed. In patients with metastatic triple-negative breast cancer who progressed after standard therapy, datopotamab deruxtecan demonstrated a good initial response and disease control rate, and has the potential to become a novel treatment option for this group of patients.
Reminder: Many types of new anti-cancer drugs bring new vitality to the treatment of breast cancer, helping patients prolong their survival and improve their quality of life.
