PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-Negative Metastatic Breast Cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adjuvant Olaparib for Germline BRCA Carriers With HER2-Negative Early Breast Cancer: Evidence and Controversies.

In the OlympiA study, 1 year of adjuvant olaparib significantly extended invasive disease-free survival and overall survival. The benefit was consistent across subgroups, and this regimen is now recommended after chemotherapy for germline BRCA1/2 mutation (gBRCA1/2m) carriers with high-risk, HER2-negative early breast cancer. However, the integration of olaparib in the landscape of agents currently available in the post(neo)adjuvant setting-ie, pembrolizumab, abemaciclib, and capecitabine-is challenging, as there are no data suggesting how to select, sequence, and/or combine these therapeutic approaches. Furthermore, it is unclear how to best identify additional patients who could benefit from adjuvant olaparib beyond the original OlympiA criteria. Since it is unlikely that new clinical trials will answer these questions, recommendations for clinical practice can be made through indirect evidence. In this article, we review available data that could help guide treatment decisions for gBRCA1/2m carriers with high-risk, early-stage breast cancer.

Identifying Patterns and Barriers in OncotypeDX Recurrence Score Testing in Older Patients With Early-Stage, Estrogen Receptor-Positive Breast Cancer: Implications for Guidance and Reimbursement.

PURPOSE: To evaluate the clinical patterns of utilization of OncotypeDX Recurrence Score (RS) in early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (BC) at an academic center with previously established internal reflex testing guidelines. METHODS: RS testing in accordance with preexisting reflex criteria and predictors of utilization outside of reflex criteria were retrospectively analyzed for the years 2019-2021 in a quality improvement evaluation. Patients were grouped according to OncotypeDX testing within (cohort A) or outside (cohort B) of predefined criteria which included a cap at age older than 65 years. RESULTS: Of 1,687 patients whose tumors had RS testing, 1,087 were in cohort A and 600 in cohort B. In cohort B, nearly half of patients were older than 65 years (n = 279; IQR, 67-72 years). For patients older than 65 years, those with RS testing were younger (median age: 69 v 73 years), with higher grade cancers (G2-3: 84.9% v 54.7%) and were more likely to be treated with chemotherapy (15.4% v 4.1%). Issues for implementation of RS testing in older patients were identified, including potential structural barriers related to the current policy on the reimbursements of genomic tests. CONCLUSION: Internal guidelines may facilitate standardized utilization of the RS in early-BC. Our data suggest that clinicians preferred broader utilization of RS across the age spectrum, with therapeutically important consequences. Modifying the current policy for reimbursement of RS testing and in internal reflexive testing criteria for those older than 65 years is warranted.

Auricular Acupuncture During Chemotherapy Infusion in Breast Cancer Patients: A Feasibility Study.

Introduction: Breast cancer patients undergoing chemotherapy experience multiple distressing symptoms. The authors investigated the feasibility and potential benefits of auricular acupuncture during chemotherapy infusion in this population. Materials and Methods: Women with stage I-III breast cancer undergoing chemotherapy were enrolled and followed for three chemotherapy cycles. During the first cycle of chemotherapy that participants received after study enrollment, they were provided with educational materials. During the second and third cycles of chemotherapy after enrollment, they received auricular acupuncture. The primary outcome was feasibility, assessed by recruitment, retention, and completion of assessments. Secondary outcomes included symptom burden (Edmonton Symptom Assessment System-Revised Version) and anxiety (State-Trait Anxiety Inventory-State), assessed at four timepoints for each cycle: day 1, pre-education/acupuncture (T1); day 1, post-education/acupuncture (T2); day 2 (T3); and day 5 (T4). Nausea and vomiting (Multinational Association of Supportive Care in Cancer [MASCC] Antiemesis Tool) were assessed on days 2 and 5. Paired t test was used to compare patient-reported outcomes during cycle 1 (education) versus an average of outcomes during cycles 2 and 3 (acupuncture). Results: Twenty-six patients were enrolled, of which 24 completed all acupuncture sessions and 22 completed all outcome assessments. In cycles 2 and 3 versus cycle 1, participants experienced significant reductions in symptom burden (change from T1 to T4: -7.9 ± 13.6, p = 0.02), anxiety (change from T1 to T2: -3.3 ± 6.5, p = 0.02), and nausea severity on day 2 (-1.3 ± 2.6, p = 0.04). Conclusions: The delivery of auricular acupuncture during chemotherapy infusion was feasible and associated with reduction of symptom burden, anxiety, and nausea in breast cancer patients. Larger-scale clinical studies are needed to confirm these findings. Clinical Trial Registration number: NCT03170648.

Weathering the Storm: Managing Older Adults With Breast Cancer Amid COVID-19 and Beyond.

Caring for older patients with breast cancer presents unique clinical considerations because of preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the "new normal" for the approximately 30% of breast cancer patients aged 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease.

Extended therapy with letrozole and ovarian suppression in premenopausal patients with breast cancer after tamoxifen.

INTRODUCTION: In premenopausal women with breast cancer, standard adjuvant endocrine therapy has been 5 years of tamoxifen. This study sought to investigate the safety and feasibility of treating patients who remain premenopausal after adjuvant tamoxifen with gonadotropin-releasing hormone agonist (GnRH-a) concurrent with an aromatase inhibitor, mimicking the strategy that has proven effective in postmenopausal patients. PATIENTS AND METHODS: This phase II single-arm clinical trial aimed to enroll 50 premenopausal women who had completed > 4.5 years of adjuvant tamoxifen for a 2-year course of leuprolide (7.5 mg intramuscularly monthly or 22.5 mg intramuscularly every 3 months) and letrozole (2.5 mg orally daily). Zoledronic acid (4 mg intravenously every 6 months) was offered optionally to help prevent bone loss. RESULTS: Despite aggressive recruitment strategies at the 3 participating sites (including Dana-Farber Cancer Institute), poor accrual over 3.5 years ultimately led to early study closure after only 16 patients began therapy. Of the 16, 4 stopped treatment before 1 year, owing to toxicity; 5 completed 2 years of protocol-directed therapy; and 7 remained on treatment as of September 1, 2013, for an average of 53.5 weeks (SD, 17.2 weeks). Hot flashes, vaginal dryness, and pain were common toxicities. CONCLUSION: Extended therapy with GnRH-a and an aromatase inhibitor (plus optional bisphosphonate) is associated with substantial side effects in premenopausal women who have already completed > 4.5 years of adjuvant tamoxifen. This study's poor accrual suggests that young women may not be highly motivated to pursue lengthier courses of endocrine therapy and that future studies of this approach may be challenging.