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.
Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor–positive/human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting.
The randomized multicenter phase II PACE trial enrolled patients with hormone receptor–positive/HER2– MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P.
Overall, 220 patients were randomly assigned between September 2017 and February 2022. The median age was 57 years (range, 25-83 years). Most patients were postmenopausal (80.9%), and 40% were originally diagnosed with de novo MBC. Palbociclib was the most common previous CDK4/6i (90.9%). The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = .62). The median PFS on F + P + A was 8.1 months (HR v F, 0.75 [90% CI, 0.50 to 1.12]; P = .23). The difference in PFS with F + P and F + P + A versus F was greater among patients with baseline ESR1 and PIK3CA alterations.
The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor–positive/HER2– MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.
It seems donepezil did not show any cognitive benefit when added to standard adjuvant chemotherapy for breast cancer. Unfortunately, adequate treatment for ‘chemo-brain’ remains elusive. There is data that a lipid structure, S1P, may be linked to this process and may be ‘druggable’ with some of the MS agents.
Datopotamab Deruxtecan is a new ADC that will likely be approved in the near future. The payload is the same as used in Enhertu, but the antibody is directed at TROP2. This report is from the TROPION-pan tumor study and shows a promising ORR in HR+/HER2- MBC. There is reasonable data for this compound in 2L met-NSCLC in the TROPION-LUNG01 study with an improvement in PFS compared to docetaxel of 4.4 vs 3.7 months. Dato also is effective in patients with actionable genetic alterations in the 2L setting. There is also an ongoing study on its use in the 1L setting for met-NSCLC in combination with pembrolizumab and chemotherapy.
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.
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.
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.
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