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.

Real-world effectiveness of palbociclib plus endocrine therapy in HR+/HER2- advanced breast cancer: final results from the POLARIS trial.

BACKGROUND: Strict eligibility criteria for participation in randomized clinical trials (RCTs) often limit the generalizability of data when applied to a more heterogeneous real-world population. Thus, evidence generated directly from real-world populations, including subgroups underrepresented in RCTs, can help inform routine clinical practice. POLARIS (NCT03280303), a prospective, observational, multicenter, cohort study, evaluated patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) receiving palbociclib + endocrine therapy (ET) in routine care. METHODS: Demographics, baseline characteristics, and treatment patterns were summarized descriptively. Real-world response and clinical benefit rates, real-world progression-free survival (rwPFS), and overall survival (OS) were summarized descriptively by line of therapy and endocrine partner in the overall cohort and various subgroups. RESULTS: Between January 2017 and October 2019, 1250 patients (median age of 64.0 years) initiated treatment with palbociclib-based therapy, including 901 in the first-line (1L) setting and 349 in the second-line or later (≥2L) settings. Real-world response and clinical benefit rates with palbociclib + ET were 34.0% and 69.4%, respectively, in 1L, and 21.8% and 57.9% in ≥2L. Median rwPFS was 20.9 (95% CI, 18.7-24.7) and 13.5 (10.6-17.1) months, and median OS was 48.5 (42.0-not estimable) and 37.2 (31.2-40.8) months, with 1L and ≥2L palbociclib + ET, respectively. CONCLUSIONS: Outcomes in this large, heterogeneous, real-world population are generally consistent with previously reported results from clinical trials and other real-world studies, further supporting the use of palbociclib + ET in patients with HR+/HER2- ABC. TRIAL REGISTRATION: NCT03280303 (ClinicalTrials.gov).

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.

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.

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.

Impact of adjuvant endocrine therapy in older patients with comorbidities and estrogen receptor-positive, node-negative breast cancer-A National Cancer Database analysis.

BACKGROUND: Data are lacking about the benefit of adjuvant endocrine therapy (ET) in older patients with multiple comorbidities. The authors sought to determine the effect of ET on the survival of older patients who had multiple comorbidities and estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, pathologic node-negative (pN0) breast cancer. METHODS: Women aged ≥70 years in the National Cancer Database (2010-2014) with Charlson/Deyo comorbidity scores of 2 or 3 who had pathologic tumor (pT1)-pT3/pN0, ER-positive/HER2-negative breast cancer were divided into 2 cohorts: adjuvant ET and no ET. Propensity scores were used to match patients based on age, comorbidity score, facility type, pT classification, chemotherapy, surgery, and radiation therapy. A Cox proportional hazards model was used to estimate the effect of ET on overall survival (OS). RESULTS: In the nonmatched cohort (n = 3716), 72.8% of patients received ET (n = 2705), and 27.2% did not (n = 1011). The patients who received ET were younger (mean age, 76 vs 79 years; P < .001) and had higher rates of breast conservation compared with those who did not receive ET (lumpectomy plus radiation: 43.4% vs 23.8%, respectively; P < .001). In the matched cohort (n = 1972), the median OS was higher in the ET group (79.2 vs 67.7 months; P < .0001). In the adjusted analysis, ET was associated with improved survival (hazard ratio, 0.70; 95% CI, 0.59-0.83). CONCLUSIONS: In older patients who have pN0, ER-positive/HER2-negative breast cancer with comorbidities, adjuvant ET was associated with improved OS, which may have been overestimated given the confounders inherent in observational studies. To optimize outcomes in these patients, current standard recommendations should be considered stage-for-stage based on life expectancy and the level of tolerance to treatment.

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer.

BACKGROUND: To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). METHODS: Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014-2019). RESULTS: Of 284 women with EBC (stage I-III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline-based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P < .001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P = .009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P = .005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline-based regimens reported MSVS hot flashes (32% vs 7%) (P = .001) and myalgia (38% vs 18%) (P = .02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P = .006) and lower percentages reported abdominal pain (13% vs 28%) (P = .02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P = .19), dose reductions (34% vs 31%; P = .50), dose delays (22% vs 25%; P = .59), or early treatment discontinuation (16% vs 16%; P = .9546). CONCLUSIONS: Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events. LAY SUMMARY: In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events.

A phase II study of Mirvetuximab Soravtansine in triple-negative breast cancer.

Folate receptor alpha (FRα) has been reported to be expressed in up to 80% of triple-negative breast cancers (TNBC) with limited expression in normal tissues, making it a promising therapeutic target. Mirvetuximab soravtansine (mirvetuximab-s) is an antibody drug conjugate which has shown promise in the treatment of FRα-positive solid tumors in early phase clinical trials. Herein, are the results of the first prospective phase II trial evaluating mirvetuximab-s in metastatic TNBC. Patients with advanced, FRα-positive TNBC were enrolled on this study. Mirvetuximab-s was administered at a dose of 6.0 mg/kg every 3 weeks. 96 patients with advanced TNBC consented for screening. FRα staining was performed on tumor tissue obtained from 80 patients. The rate of FRα positivity by immunohistochemistry was 10.0% (8/80). Two patients were treated on study, with best overall responses of stable disease in one and progressive disease in the other. Adverse events were consistent with earlier studies. The study was terminated early due to the low rate of FRα positivity in the screened patient population and lack of disease response in the two patients treated. The observed rate of FRα positivity was considerably lower than previously reported and none of the patients had a partial or complete response. Treatment with mirvetuximab-s should only be further explored in TNBC if an alternate biomarker strategy is developed for patient selection on the basis of additional preclinical data.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

BACKGROUND: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. METHODS: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. RESULTS: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. CONCLUSIONS: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

POLARIS: a prospective, multicenter, noninterventional study assessing palbociclib in hormone receptor-positive advanced breast cancer.

This report describes the rationale, purpose and design of the POLARIS study. POLARIS is an ongoing noninterventional, prospective, multicenter study. Female and male patients in the USA and Canada diagnosed with hormone receptor-positive/HER2-negative metastatic breast cancer were enrolled in the study and treated with the cyclin-dependent kinase 4/6 inhibitor palbociclib when hormone receptor-positive/HER2-negative metastatic breast cancer was deemed to be indicated by their physician. The study will provide real-world data on palbociclib prescribing and treatment patterns in routine clinical practice, associated clinical outcomes, treatment sequencing in the advanced/metastatic setting, patient quality of life and geriatric-specific assessments. The tumor genomic landscape in relation to clinical outcomes will be explored. POLARIS will identify benefits and side effects of palbociclib across multiple lines of therapy and in discrete subsets of patients. Clinical Trial Registration: NCT03280303 (ClinicalTrials.gov).

Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: Current clinical practice.

BACKGROUND: In the current study, the authors investigated the incidence of moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient-reported and clinician-assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified. METHODS: Patients completed a Patient-Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy. RESULTS: The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti-human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti-HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient-reported and clinician-assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient-reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06-2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72-4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37-0.887 [P = .01]) was found to be associated with lower CIPN severity. CONCLUSIONS: The discrepancy between patient-reported and clinician-assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose-limiting, and potentially disabling side effect of chemotherapy.

Patient-Reported Toxicities During Chemotherapy Regimens in Current Clinical Practice for Early Breast Cancer.

BACKGROUND: This study explores the incidence of patient-reported major toxicity-symptoms rated "moderate," "severe," or "very severe"-for chemotherapy regimens commonly used in early breast cancer. PATIENTS AND METHODS: Female patients aged 21 years or older completed a validated Patient-Reported Symptom Monitoring instrument and rated 17 symptoms throughout adjuvant or neoadjuvant chemotherapy. Fisher's exact tests compared differences in percentages in symptom ratings, and general linear regression was used to model the incidence of patient-reported major toxicity. RESULTS: In 152 patients, the mean age was 54 years (range, 24-77), and 112 (74%) were white; 51% received an anthracycline-based regimen. The proportion of patients rating fatigue, constipation, myalgia, diarrhea, nausea, peripheral neuropathy, and swelling of arms or legs as a major toxicity at any time during chemotherapy varied significantly among four chemotherapy regimens (p < .05). The mean (SD) number of symptoms rated major toxicities was 6.3 (3.6) for anthracycline-based and 4.4 (3.5) for non-anthracycline-based regimens (p = .001; possible range, 0-17 symptoms). Baseline higher body mass index (p = .03), patient-reported Karnofsky performance status ≤80 (p = .0003), and anthracycline-based regimens (p = .0003) were associated with greater total number of symptoms rated major toxicities (alternative model: chemotherapy duration, p < .0001). Twenty-six percent of dose reductions (26 of 40), 75% of hospitalizations (15 of 20), and 94% of treatment discontinuations (15 of 16) were in anthracycline-based regimens. CONCLUSION: Capturing multiple toxicity outcomes throughout chemotherapy enables oncologists and patients to understand the range of side effects as they discuss treatment efficacies. Continuous symptom monitoring may aid in the timely development of interventions that minimize toxicity and improve outcomes. IMPLICATIONS FOR PRACTICE: This study investigated patient-reported toxicities for 17 symptoms recorded prospectively during adjuvant and neoadjuvant chemotherapy regimens for early breast cancer. An analysis of four commonly used chemotherapy regimens identified significant differences among regimens in both individual symptoms and total number of symptoms rated moderate, severe, or very severe. Longer chemotherapy regimens, such as anthracycline-based regimens followed by paclitaxel, had higher proportions of symptoms rated major toxicities. The inclusion of patient perspectives on multiple toxicity outcomes at the same time at multiple time points during chemotherapy has the potential for improving patient-provider communication regarding symptom management, patient satisfaction, and long-term clinical outcomes.

Potentially inappropriate medication use in older patients with breast and colorectal cancer.

BACKGROUND: The objective of this study was to determine patient characteristics associated with potentially inappropriate medication (PIM) use and its impact on outcomes for patients with breast or colorectal cancer receiving adjuvant chemotherapy. METHODS: The Surveillance, Epidemiology, and End Results database, linked to Medicare claims, was used. The cohort included patients who were 66 years old or older and were diagnosed with stage II or III breast or colorectal cancer between July 1, 2007, and December 31, 2009. The Drugs to Avoid in the Elderly (DAE) list and the Beers criteria were used to identify PIM use. Univariate/multivariate logistic regression determined the association of baseline PIMs with covariates. Event-free survival (EFS) was defined as the time from chemotherapy initiation to the first emergency room (ER) visit, hospitalization, death, or a composite until 3 months after chemotherapy. Cox proportional hazards modeling determined the association of PIMs with EFS. RESULTS: The analysis included 1595 patients with breast cancer and 1528 patients with colorectal cancer. The baseline PIM frequencies were 22.2% (according to the DAE list) and 27.6% (according to the Beers criteria) in the breast cohort and 15.5% (according to the DAE list) and 24.8% (according to the Beers criteria) in the colorectal cohort. Among patients with breast cancer, 37.5% had at least 1 adverse outcome; associations included the use of ≥5 medications, an advanced stage, higher comorbidity, and prior ER visits/hospitalizations. Baseline PIM use according to the DAE list was associated with an increased risk of death in patients with breast cancer. Among patients with colorectal cancer, 45% had at least 1 adverse outcome, and associations included the use of ≥5 medications, older age, female sex, and higher comorbidity. A time-to-event analysis revealed no association between baseline PIM use and most outcomes. CONCLUSIONS: These findings require further prospective confirmation, but they support a correlation between polypharmacy and adverse outcomes for cancer patients and call into question the association with PIMs. Cancer 2018;124:3000-7. © 2018 American Cancer Society.

Fractures frequently occur in older cancer patients: the MD Anderson Cancer Center experience.

PURPOSE AND INTRODUCTION: A growing number of cancer patients are older adults aged 65 years and older. Patients with cancer are at increased risk for developing osteoporosis, falls, and fractures. We sought to identify the incidence of fractures in older adults who underwent cancer care between January 2013 and December 2015. METHODS: A comprehensive geriatric assessment was performed, and bone densitometry was measured at baseline, with a 2-year follow-up. RESULTS: In this study, among 304 patients with gastrointestinal, urologic, breast, lung, and gynecologic cancers we evaluated, and who completed the bone density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia). There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p = 0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was identified in 49% of tested cases (n = 245). Risk factors for low bone mass or osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than reported in individuals without cancer. Risk factors for fractures included advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03). CONCLUSION: Most older cancer patients studied have osteoporosis or low bone mass, resulting in an almost 3-fold increase in fracture risk as compared to epidemiologic studies. Bone health issues are commonly seen in older cancer patients, we recommend universal bone density testing. The initiation of antiresorptive treatment when findings are of osteopenia or osteoporosis will reduce the risk of fractures.

Impact of androgen receptor expression in fluoxymesterone-treated estrogen receptor-positive metastatic breast cancer refractory to contemporary hormonal therapy.

PURPOSE: The purpose of this study is to evaluate survival outcome in patients with hormone receptor (HR)-positive (+) metastatic breast cancer (MBC) who received fluoxymesterone after disease progression while receiving contemporary hormonal therapy, as well as the association between estrogen receptor (ER)/androgen receptor (AR) status and survival outcome in these patients. METHODS: We retrospectively identified 103 patients treated with fluoxymesterone for HR + MBC from 2000 to 2014 and with at least one previous hormonal therapy in a metastatic setting. RESULTS: A median of 3 (range 1-10) hormonal therapies (aromatase inhibitors, tamoxifen, and/or fulvestrant) were received before fluoxymesterone; 33 patients discontinued fluoxymesterone before progression because of physician decision or adverse events including toxicity in 14 patients. Of the remaining 70 patients, 2 (3 %) had complete response, 7 (10 %) partial response, and 21 (30 %) stable disease for at least 6 months, yielding a clinical benefit rate of 43 %. The median PFS was 3.9 months (95 % CI 3.2-5.3 months). Multivariate analysis revealed no significant association between PFS and the type or number of prior systemic treatments. All 39 patients who had archived tumor slides available for AR staining had ER + carcinoma; 10 had ≥1 % but <10 %, 18 had ≥10 %, and 11 had no AR nuclear expression. AR positivity with various cutoffs (i.e. any AR + cells, ≥1 % AR + cells, or ≥10 % AR + cells) was not significantly associated with survival outcome. CONCLUSIONS: Fluoxymesterone can be considered for patients whose ER + MBC progresses on contemporary hormonal therapy, regardless of the level of AR expression.

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.

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.

High-dose chemotherapy and autologous stem cell transplantation for nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma that is characterized by unique clinical presentation, histological appearance, and indolent disease course. The recurrent nature of disease provides an opportunity to examine the role of stem cell transplantation in its management. We report here a single-center experience of 26 patients with relapsed NLPHL treated with high-dose chemotherapy and autologous stem cell transplantation between 1990 and 2008. With a median follow-up of 50 months (range, 2-138 months), the 5-year overall and event-free survival were 76% (SE 10%) and 69% (SE 10%), respectively. Our data suggest that high-dose chemotherapy and autologous transplantation should be considered as an option for patients with relapsed NLPHL.

Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer.

BACKGROUND: The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer. METHODS: Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS. RESULTS: Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P = .019 and P < .001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively (P = .06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P = .15). A high copy number for either gene was not found to be an independent predictor of RFS. CONCLUSIONS: A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS.