Nicely done study comparing Ribociclib + ET vs chemotherapy in premenopausal high-risk HR+, HER2-neg patients felt to be high risk. Results showed better efficacy (PFS), tolerability and similar response rates. Of note, >80% of patients had visceral disease or were felt to be rapid progressors. Anti-hormone-based therapy remains king in the HR+ setting.
A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC).
In this open-label, multi-center, randomized phase 2 trial, pre/perimenopausal women with clinically aggressive HR+/HER2− ABC were randomized 1:1 to first-line ribociclib (600 mg daily; 3-weeks-on, 1-week-off) plus letrozole/anastrozole and goserelin or investigator’s choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary endpoint was progression-free survival (PFS).
Among 222 patients randomized to ribociclib plus ET (n=112) or combination CT (n=110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator’s judgment, and 31 (14.0%) had symptomatic non-visceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. Median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; 95% CI, 17.4-26.7 months) and 12.8 months (combination CT; 95% CI, 10.1-18.4 months); hazard ratio [HR], 0.61; 95% CI, 0.43-0.87; P=.003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (HR, 0.76; 95% CI, 0.55-1.06). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm
First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2− ABC.
Noteworthy NCCI database study showing zip code has a negative influence on tumor burden and outcomes. I wonder if the presence of community oncology practices in similar geographical zones reduces this interaction of environmental opportunity and outcomes.
Findings from the PACE study show that the addition of Palbociclib to Fulvestrant was not better than Fulvestrant alone, and the addition of Avelumab to Fulvestrant improved and nearly doubled the PFS. This is compelling and should be studied further for our patients with HR+ HER2- MBC.
For your stage II – III HR+, HER2-neg breast cancer patients. Adjuvant Ribociclib + AI showed a ~3% invasive DFS benefit vs. an AI alone (90 vs 87%). This is a 3-year treatment protocol as opposed to 5 years of an AI, which some patients may appreciate.
This is a study showing tumor agnostic activity of trastuzumab deruxtecan (T-DXd) with an all-comer overall response rate (ORR) of 37.1%, duration of response (DOR) of 11.3 months and an overall survival (OS) of 13.4 months in an otherwise heavily pre-treated group. Those with IHC-3+ derived larger benefit than 2+. Patients with ERBB2 mutations who had no expression of HER2 were excluded from the trial.
There have been studies showing decreased recurrence in women who underwent curative breast surgeries (walking and yoga). This study assesses if it will affect the intensity of chemotherapy delivered. Although it did not affect it, women who underwent the program had better pathologic complete response (pCR), we need more studies to assess role of nutrition and exercise in treating cancer as we develop a wholesome approach to treat our patients, something we may be able to do in our practice.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
