A systematic review of health-related quality of life outcomes in patients with advanced breast cancer treated with palbociclib.

Aim: To evaluate the impact of palbociclib treatment on health-related quality of life (HRQoL) in patients with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer (HR+/HER2- aBC) or metastatic breast cancer (mBC) in both the clinical and real-world setting. Materials & methods: A systematic literature review was conducted to identify clinical trials and real-world evidence studies up to June 2023 that reported HRQoL outcomes in patients with HR+/HER2- aBC or mBC treated with Palbociclib. Results: 15 unique studies reported across 35 records were identified. Of these, seven were randomized controlled trials (RCTs), three were single-arm clinical trials and five were real-world evidence (RWE) studies. HRQoL was generally found to be maintained in patients with HR+/HER2- aBC or mBC across RCTs, single-arm clinical trials and RWE studies. HRQoL measures across instruments, study types and line of therapy, were largely reported to be at least maintained if not improved from baseline among patients treated with palbociclib and were observed to be comparable or better in the palbociclib group versus monotherapy control arm in RCTs. Similar results were seen for treatment-related outcomes (e.g., sexual functioning, upset by hair loss, systemic therapy side effects etc.), and important individual patient outcomes, including pain, fatigue and physical functioning. Findings were also consistent across key clinical characteristics (visceral metastases, neutropenia), as well as patient populations often underrepresented in clinical trials (Asian patients, older adults). Conclusion: Overall, current evidence suggests that HRQoL is largely preserved with the addition of palbociclib to endocrine therapy in patients with HR+/HER2- aBC or mBC across study types and populations.

Clinical Outcomes in Patients with Early Stage Node-Negative HER2-Positive Breast Cancer Receiving Upfront Surgery or Neoadjuvant Systemic Therapy.

BACKGROUND: HER2-positive breast cancer is traditionally treated with neoadjuvant systemic therapy (NST), but optimal treatment sequencing is less clear in patients with small tumors. We investigated clinicopathologic and oncologic outcomes in early stage HER2-positive breast cancer. PATIENTS AND METHODS: An institutional database was queried to identify patients with cT1-2 (≤ 3 cm) N0M0, HER2-positive breast cancer treated from 2015 to 2020 and compared upfront surgery and NST cohorts. Logistic regression was performed to identify factors predicting upstaging. Survival outcomes by group were compared using log-rank tests. RESULTS: Of 256 patients identified, 170 (66.4%) received upfront surgery and 86 (33.6%) NST. The NST cohort was younger and had more cT2 and grade 3 tumors and negative sentinel nodes. There was no significant difference in type of breast surgery or receipt of axillary lymphadenectomy. After upfront surgery, 4 (2.4%) patients had upstaging to pT > 3 cm and 18 (10.6%) to pN1-3. No factors predicted upstaging. After NST, 47 (54.7%) achieved pathologic complete response and 3 (3.5%) had upstaging to ypN1-3 with older age (OR 1.08, p = 0.004) and hormone receptor-positive status (OR 7.07, p = 0.002) identified as predictors. At median follow-up of 3.55 years, 10 (3.9%) patients had recurrence and 5 (2.0%) patients died. There were no significant differences in oncologic outcomes between groups. CONCLUSIONS: Patients with cT1-2 (≤ 3 cm)N0 HER2-positive breast cancer selected for NST have higher-risk disease. Low rates of pathologic upstaging were observed with no difference in surgical treatments and overall excellent oncologic outcomes in both groups. These findings may guide decision-making regarding treatment sequencing for patients with early stage HER2-positive disease.

Patient-reported convenience and effectiveness of telehealth for breast cancer management.

BACKGROUND: Before the coronavirus disease 2019 (COVID-19) pandemic, telehealth was rarely used for breast cancer management at tertiary care centers. We sought to examine patient satisfaction, experiences, preferences, and perceived effectiveness and technical quality of telehealth visits in follow-up patients receiving routine outpatient care in the breast medical oncology practice at The University of Texas MD Anderson Cancer Center. METHODS: We administered a survey to 60 follow-up patients for a duration of 9 months (January 5, 2021 to October 27, 2021) who had at least one telehealth consultation during the COVID-19 pandemic, from April 10, 2020 to October 21, 2021. Descriptive statistics were then generated for each question, each domain, and overall survey scores. Subgroup comparisons within patient populations were done using the chi-square or t-test when appropriate. RESULTS: Among the 60 participants, 49 (82%) were undergoing standard follow-up during active treatment for either early-stage or metastatic breast cancer. Telehealth and in-person office visits were considered equivalent in terms of quality of communication by 43 participants (72%). Most participants (n = 49, 82%) felt equally cared for during telehealth and in-person visits, and 40 participants (67%) reported feeling connected to their healthcare professional during both telehealth and in-person visits. In addition, 28 participants (47%) felt that the duration of telehealth visits was similar to in-person visits, 46 (77%) found both telehealth and in-person visits equally comfortable for discussing sensitive topics, 39 (65%) considered telehealth visits convenient, and 42 (70%) perceived the overall quality of care for telehealth to be similar to that of in-person visits. Participants expressed high satisfaction with telehealth appointments, with 42 (70%) rating their experience as very satisfying. Most participants (n = 44, 73%) expressed a strong likelihood of participating in telehealth appointments for breast cancer follow-up care in the future. CONCLUSIONS: Our results indicate that telehealth can serve as an effective and satisfactory approach for delivering healthcare services to patients with breast cancer requiring follow-up care. The positive experiences and willingness to continue using telehealth indicate its potential for improving access to care and patient outcomes.

Outcomes of older adults with early-stage triple-negative breast cancer (TNBC) receiving chemotherapy: a single-institution experience.

BACKGROUND: Despite lower chemotherapy use in older triple-negative breast cancer (TNBC) patients, their outcomes match younger counterparts. We compared outcomes in early-stage TNBC patients by age receiving chemotherapy at a major cancer center with a national TNBC database. METHODS: Retrospective study using institutional data on stage I-III TNBC (ER/PR < 10%) women with neoadjuvant/adjuvant chemotherapy. Based on their ages at diagnosis, patients were stratified into four categories: ≤40, 41-59, 60-69, and ≥ 70 years. Demographic and clinical characteristics recorded included race, disease stage, ER/PR positivity, treatment regimen, lymphatic or vascular invasion (LVI), histologic grade, Ki-67 level, body mass index (BMI), and pathologic complete response (pCR) following neoadjuvant treatment and are summarized using descriptive statistics. The primary endpoints were overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS); all were estimated using the Kaplan-Meier method. Both univariate and multivariate (MV) Cox regressions were applied to evaluate the impact of important covariates on these time-to-event endpoints. RESULTS: Of the 2336 patients studied, 492 (21.1%) were ≤ 40 years old, 1239 (53.1%) were 41-59, 461 (19.7%) were 60-69, and 144 (6.2%) were ≥ 70. In the univariate regression model of OS/DFS/DDFS, age ≥ 70 was significantly associated with worse OS (p = 0.0217); other factors associated with worse OS were non-anthracycline-based chemotherapy, higher tumor stage, and neoadjuvant chemotherapy. The multivariate Cox regression model, adjusted for race and stage, showed no significant effects of age on OS; however, patients ≥ 70 years old who received non-anthracycline treatment combinations had worse DFS (hazard ratio = 0.349 vs. 1.049, p = 0.0293) and DDFS (hazard ratio = 0.317 vs. 1.016, p = 0.0251) than patients ≤ 40 years old. DFS from MV model after adjusting for age, race, and disease stage, the hazard ratio between anthracycline + taxane treatments and anthracycline + other treatments in patients ≥ 70 years old was statistically significantly lower than in patients ≤ 40 years old (hazard ratios [HRs] = 0.349 vs. 1.049, p = 0.0293). CONCLUSIONS: Our findings indicate that outcomes such as DFS are less favorable in older compared to younger patients with early-stage TNBC, primarily in those who did not receive an anthracycline based chemotherapy regimen.

Outcomes of male patients with HR+/HER2- advanced breast cancer receiving palbociclib in the real-world POLARIS study.

PURPOSE: Data on treatments for male breast cancer patients are limited owing to rarity and underrepresentation in clinical trials. The real-world POLARIS study gathers data on palbociclib use for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in female and male patients. This sub-analysis describes real-world palbociclib treatment patterns, clinical outcomes, and quality of life (QoL) in male patients. METHODS: POLARIS is a prospective, noninterventional, multicenter, real-world study of patients with HR+/HER2- ABC receiving palbociclib. Assessments included medical record reviews, patient QoL questionnaires (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30), site characteristics questionnaires, and physician treatment selection surveys. Variables included demographics, disease history, global health status/QoL, clinical assessments and adverse events. Analyses were descriptive in nature. For clinical outcomes, real-world tumor responses and progression were determined by physician assessment in routine clinical practice. Real-world progression-free survival (rwPFS) was described using the Kaplan-Meier method. RESULTS: At data cutoff, 15 male patients were enrolled (median age, 66 years). Nine patients received palbociclib as a first-line treatment and 6 as a second-line or later treatment. Patients received a median of 20 cycles of palbociclib. Neutropenia was experienced by 2 patients and grade ≥ 3 adverse events were reported in 11 patients. Global health status/QoL scores remained generally consistent during the study. One patient (6.7%) achieved a complete tumor response, 4 (26.7%) a partial response, and 8 (53.3%) stable disease. Median rwPFS was 19.8 months (95% CI, 7.4-38.0). Median follow-up duration was 24.7 months (95% CI, 20.0-35.7). CONCLUSION: This real-world analysis showed that palbociclib was well tolerated and provides preliminary data on treatment patterns and outcomes with palbociclib in male patients with HR+/HER2- ABC, helping inform the use of palbociclib in this patient subgroup. TRIAL IDENTIFIER: NCT03280303.

Measures of functional status in older patients treated with palbociclib for advanced breast cancer.

INTRODUCTION: Limited data are available on the effects of treatment for advanced breast cancer (ABC) in older patients because this population has limited enrollment in clinical trials. Data generated from the prospective, noninterventional POLARIS study of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative ABC may help bridge the gap in our understanding of the tolerability and outcomes in this vulnerable population. MATERIALS AND METHODS: We evaluated measures of geriatric impairments and activities of daily living in patients with ABC aged ≥70 years in POLARIS to evaluate the change within six months of palbociclib initiation. Geriatric impairments and activities of daily living (functional) status were assessed using the Geriatric 8 (G8) and Activities of Daily Living (ADL) screening tools. The G8, ADL, and Eastern Cooperative Oncology Group performance status (ECOG PS) scores were assessed at baseline and month six through end of treatment with palbociclib. ECOG PS scores were also stratified by G8 and ADL score severity subgroups (G8: ≤14 = impaired subgroup; >14 = not at all impaired subgroup; ADL: <18 = dependent subgroup, 18 = independent subgroup). RESULTS: At data cutoff in November 2020, of 1282 POLARIS patients of all ages, 287 (22.4%) were ≥ 70 years old and completed ≥6 months of palbociclib therapy. At baseline, 117 (45%; n = 260) of these patients had an ECOG PS score of 0, 143 (55%; n = 260) had ECOG PS score > 0, 248 (86%) had G8 scores (mean [SD] 13.6 [2.14]), and 256 (89%) had ADL scores (17.7 [1.03]) among the available 287 patients. At six months, 102 (40%; n = 255) had an ECOG PS score of 0, 153 (60%; n = 255) had ECOG PS score > 0, 198 (69%) had G8 scores (13.6 [1.99]), and 211 (74%) had ADL scores (17.6 [1.22]) among the 287 available patients. There was no mean change (standard deviation) from baseline to 6 months in mean ECOG PS scores (0.0 [0.61], P = 0.24), G8 scores (0.0 [2.17], P = 0.89), or ADL scores (0.0 [1.00], P = 0.62). DISCUSSION: In this subgroup analysis of older patients with ABC from POLARIS, functional status and impairment outcomes were preserved in older patients receiving palbociclib. G8, ADL, and ECOG PS scores were generally maintained during the first six months of palbociclib therapy. CLINICALTRIALS: govidentification number. NCT03280303.

Real-World Analysis of Clinical and Demographic Characteristics, Treatment Patterns, and Outcomes in Predominantly Older Patients with HR+/HER2- Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients. METHODS AND MATERIALS: This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2- mBC receiving abemaciclib in US-based community oncology settings (1 September 2017 to 30 September 2019). Patients with other primary malignancies, clinical trial enrollment, and incomplete charts were excluded. Patient characteristics, treatment attributes and patterns, and real-world outcomes (clinical benefit rate [CBR] and stable disease among patients with response data available, time to chemotherapy [TTC], time to treatment discontinuation [TTD], and progression-free survival [PFS]) were summarized. Multivariable models evaluated the association between demographic/clinical characteristics and outcomes. RESULTS: Of the 448 final patients, 99% were female, with a median age of 67 years (25% were ≥ 75 years) and median follow-up of 11 months; most (60%) initiated abemaciclib within 2 years of mBC diagnosis. Patients received a median of 1 (P25 = 0, P75 = 3) prior line of therapy for mBC before abemaciclib, including other CDK4 & 6is (48%) and prior chemotherapy (31%); most (57%) had visceral disease. The CBR for the overall population was 53%, with 48% achieving stable disease. The median TTC was not reached; median TTD was 249 days (95% confidence interval [CI]: 202, 304). The median PFS was 329 days (95% CI 266, 386). The discontinuation rate of abemaciclib owing to adverse events (30%) trended higher with age (years) (P = 0.027): 18-49 (n = 42; 19%), 50-64 (n = 155; 25%), 65-74 (n = 138; 32%), 75-84 (n = 82; 37%), ≥ 85 (n = 31; 49%); only 23% of patients overall had a dose hold or reduction prior to discontinuation. CONCLUSIONS: These patients were older than those in the MONARCH studies with substantial visceral disease, and prior chemotherapy and CDK4 & 6i use. Discontinuation rates were higher than in previous real-world studies (11.9%), highlighting the need for proactive management to optimize outcomes, particularly in older patients with mBC.

A phase II study of neoadjuvant atezolizumab and nab-paclitaxel in patients with anthracycline-resistant early-stage triple-negative breast cancer.

PURPOSE: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489). METHODS: Patients with stage I-III, AC-resistant TNBC, defined as disease progression or a < 80% reduction in tumor volume after 4 cycles of AC, were eligible. Patients received atezolizumab (1200 mg IV, Q3weeks × 4) and nab-paclitaxel (100 mg/m2 IV,Q1 week × 12) as the second phase of NAT before undergoing surgery followed by adjuvant atezolizumab (1200 mg IV, Q3 weeks, × 4). A two-stage Gehan-type design was employed to detect an improvement in pCR/residual cancer burden class I (RCB-I) rate from 5 to 20%. RESULTS: From 2/15/2016 through 1/29/2021, 37 patients with AC-resistant TNBC were enrolled. The pCR/RCB-I rate was 46%. No new safety signals were observed. Seven patients (19%) discontinued atezolizumab due to irAEs. CONCLUSION: This study met its primary endpoint, demonstrating a promising signal of activity in this high-risk population (pCR/RCB-I = 46% vs 5% in historical controls), suggesting that a response-adapted approach to the utilization of neoadjuvant immunotherapy should be considered for further evaluation in a randomized clinical trial.

Characteristics and Outcomes in Cases of US Male Patients with Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Breast cancer in males constitutes approximately 1% of all breast cancer cases globally. Despite extensive treatment experience with abemaciclib in women with metastatic breast cancer (MBC), real-world evidence in male MBC is lacking. METHODS: This analysis was a part of a broader, retrospective study that analyzed electronic medical records and charts of 448 men and women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) MBC who initiated an abemaciclib-containing regimen from January 2017 through September 2019. Data were collected from the Florida Cancer Specialists & Research Institute and the Electronic Medical Office Logistics Health Oncology Warehouse Language™ databases and summarized descriptively. Real-world best response was described: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). RESULTS: Data for six male patients with MBC who were treated with abemaciclib in combination with an aromatase inhibitor (AI) or fulvestrant are presented. Four patients were aged ≥ 75 years, and four patients had ≥ 3 metastatic sites, including visceral involvement. Abemaciclib was initiated in/after third-line (≥ 3L) in four patients, and patients had history of treatment with AI (n = 4), chemotherapy (n = 3), and/or prior cyclin-dependent kinase 4 and 6 inhibitors (n = 2) in the metastatic setting. Abemaciclib + fulvestrant was the most common abemaciclib-containing regimen (n = 4). Best response was documented in four patients: 1 each with CR, PR, SD, and PD. CONCLUSION: Prevalence of male MBC in this dataset was consistent with expected prevalence in the broader population. Most male patients received an abemaciclib-containing regimen in ≥ 3L, with anti-cancer activity observed despite heavy metastatic burden and prior treatments in a metastatic setting.

Evaluation of Alisertib Alone or Combined With Fulvestrant in Patients With Endocrine-Resistant Advanced Breast Cancer: The Phase 2 TBCRC041 Randomized Clinical Trial.

Importance: Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i-resistant MBC is unknown. Objective: To assess the effect of adding fulvestrant to alisertib on objective tumor response rates (ORRs) in endocrine-resistant MBC. Design, Setting, and Participants: This phase 2 randomized clinical trial was conducted through the Translational Breast Cancer Research Consortium, which enrolled participants from July 2017 to November 2019. Postmenopausal women with endocrine-resistant, ERBB2 (formerly HER2)-negative MBC who were previously treated with fulvestrant were eligible. Stratification factors included prior treatment with CDK 4/6i, baseline metastatic tumor ERα level measurement (<10%, ≥10%), and primary or secondary endocrine resistance. Among 114 preregistered patients, 96 (84.2%) registered and 91 (79.8%) were evaluable for the primary end point. Data analysis began after January 10, 2022. Interventions: Alisertib, 50 mg, oral, daily on days 1 to 3, 8 to 10, and 15 to 17 of a 28-day cycle (arm 1) or alisertib same dose/schedule with standard-dose fulvestrant (arm 2). Main Outcomes and Measures: Improvement in ORR in arm 2 of at least 20% greater than arm 1 when the expected ORR for arm 1 was 20%. Results: All 91 evaluable patients (mean [SD] age, 58.5 [11.3] years; 1 American Indian/Alaskan Native [1.1%], 2 Asian [2.2%], 6 Black/African American [6.6%], 5 Hispanic [5.5%], and 79 [86.8%] White individuals; arm 1, 46 [50.5%]; arm 2, 45 [49.5%]) had received prior treatment with CDK 4/6i. The ORR was 19.6%; (90% CI, 10.6%-31.7%) for arm 1 and 20.0% (90% CI, 10.9%-32.3%) for arm 2. In arm 1, the 24-week clinical benefit rate and median progression-free survival time were 41.3% (90% CI, 29.0%-54.5%) and 5.6 months (95% CI, 3.9-10.0), respectively, and in arm 2 they were 28.9% (90% CI, 18.0%-42.0%) and 5.4 months (95% CI, 3.9-7.8), respectively. The most common grade 3 or higher adverse events attributed to alisertib were neutropenia (41.8%) and anemia (13.2%). Reasons for discontinuing treatment were disease progression (arm 1, 38 [82.6%]; arm 2, 31 [68.9%]) and toxic effects or refusal (arm 1, 5 [10.9%]; arm 2, 12 [26.7%]). Conclusions and Relevance: This randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase ORR or PFS; however, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and CDK 4/6i-resistant MBC. The overall safety profile was tolerable. Trial Registration: ClinicalTrials.gov Identifier: NCT02860000.