FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRα-Positive, Platinum-Resistant Ovarian Cancer.

On November 14, 2022, the FDA granted accelerated approval to mirvetuximab soravtansine-gynx for treatment of adult patients with folate receptor-α (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic therapies. The VENTANA FOLR1 (FOLR-2.1) RxDx Assay was approved as a companion diagnostic device to select patients for this indication. Approval was based on Study 0417 (SORAYA, NCT04296890), a single-arm, multicenter trial. In 104 patients with measurable disease who received mirvetuximab soravtansine-gynx, the overall response rate was 31.7% [95% confidence interval (CI), 22.9-41.6] with a median duration of response of 6.9 months (95% CI, 5.6-9.7). Ocular toxicity was included as a Boxed Warning in the U.S. Prescribing Information (USPI) to alert providers of the risks of developing severe ocular toxicity including vision impairment and corneal disorders. Pneumonitis and peripheral neuropathy were additional important safety risks included as Warnings and Precautions in the USPI. This is the first approval of a targeted therapy for FRα-positive, platinum-resistant ovarian cancer and the first antibody-drug conjugate approved for ovarian cancer. This article summarizes the favorable benefit-risk assessment leading to FDA's approval of mirvetuximab soravtansine-gynx.

US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer.

PURPOSE: The US Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd) for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1 + or immunohistochemistry 2+/in situ hybridization-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. PATIENTS AND METHODS: Approval was based on DESTINY-Breast04, a phase III, randomized, open-label, multicenter trial in patients with unresectable or metastatic HER2-low breast cancer, determined at a central laboratory. A total of 557 patients were randomly assigned (2:1) to receive either T-DXd 5.4 mg/kg intravenously once every 3 weeks (n = 373) or physicians' choice of chemotherapy (n = 184). RESULTS: The study met its primary efficacy end point of progression-free survival (PFS) by blinded independent central review assessment in the hormone receptor-positive (HR+) cohort (N = 494) with an estimated hazard ratio (HR) of 0.51(95% CI, 0.40 to 0.64; P < .0001). Key secondary end points were also met, including PFS in the intent-to-treat population with an HR of 0.50 (95% CI, 0.40 to 0.63; P < .0001), overall survival (OS) in the HR+ cohort with an HR of 0.64 (95% CI, 0.48 to 0.86; P = .0028) and OS in the intent-to-treat with an HR of 0.64 (95% CI, 0.49 to 0.84; P = .0010). The safety profile of T-DXd was consistent with previously approved indications, and no new safety signals were observed in this study population. CONCLUSION: The approval of T-DXd in HER2-low metastatic breast cancer was based on statistically significant and clinically meaningful PFS and OS improvements observed in the DESTINY-Breast04 trial and represents the first approved therapy specifically for the treatment of HER2-low metastatic breast cancer.

Highlights of FDA Oncology Approvals in 2022: Tissue-Agnostic Indications, Dosage Optimization, and Diversity in Drug Development.

In 2022, cancer drug development continued to progress rapidly despite the lingering COVID-19 pandemic. Highlights of U.S. drug approvals for oncology indications this year include ongoing development in rare diseases and molecular subgroups, improved dosage optimization, and updated data for drugs granted accelerated approval, with confirmatory studies demonstrating verification of clinical benefit in some instances, as well as indication withdrawal when clinical benefit was not verified.

HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane.

PURPOSE: To assess whether crofelemer would prevent chemotherapy-induced diarrhea (CID) diarrhea in patients with HER2-positive, any-stage breast cancer receiving trastuzumab (H), pertuzumab (P), and a taxane (T; docetaxel or paclitaxel), with/without carboplatin (C; always combined with docetaxel rather than paclitaxel). METHODS: Patients scheduled to receive ≥ 3 consecutive TCHP/THP cycles were randomized to crofelemer 125 mg orally twice daily during chemotherapy cycles 1 and 2 or no scheduled prophylactic medication (control). All received standard breakthrough antidiarrheal medication (BTAD) as needed. The primary endpoint was incidence of any-grade CID for ≥ 2 consecutive days. Secondary endpoints were incidence of all-grade and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; use of BTAD; and quality of life (Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea [FACIT-D] score). RESULTS: Fifty-one patients were randomized to crofelemer (n = 26) or control (n = 25). There was no statistically significant difference between arms for the primary endpoint; however, incidence of grade ≥ 2 CID was reduced with crofelemer vs control (19.2% vs 24.0% in cycle 1; 8.0% vs 39.1%, in cycle 2). Patients receiving crofelemer were 1.8 times more likely to see their diarrhea resolved and had less frequent watery diarrhea. CONCLUSION: Despite the choice of primary endpoint being insensitive, crofelemer reduced the incidence and severity of CID in patients with HER2-positive breast cancer receiving P-based therapy. These data are supportive of further testing of crofelemer in CID. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02910219, prospectively registered September 21, 2016.

Associating persistent self-reported cognitive decline with neurocognitive decline in older breast cancer survivors using machine learning: The Thinking and Living with Cancer study.

INTRODUCTION: Many cancer survivors report cognitive problems following diagnosis and treatment. However, the clinical significance of patient-reported cognitive symptoms early in survivorship can be unclear. We used a machine learning approach to determine the association of persistent self-reported cognitive symptoms two years after diagnosis and neurocognitive test performance in a prospective cohort of older breast cancer survivors. MATERIALS AND METHODS: We enrolled breast cancer survivors with non-metastatic disease (n = 435) and age- and education-matched non-cancer controls (n = 441) between August 2010 and December 2017 and followed until January 2020; we excluded women with neurological disease and all women passed a cognitive screen at enrollment. Women completed the FACT-Cog Perceived Cognitive Impairment (PCI) scale and neurocognitive tests of attention, processing speed, executive function, learning, memory and visuospatial ability, and timed activities of daily living assessments at enrollment (pre-systemic treatment) and annually to 24 months, for a total of 59 individual neurocognitive measures. We defined persistent self-reported cognitive decline as clinically meaningful decline (3.7+ points) on the PCI scale from enrollment to twelve months with persistence to 24 months. Analysis used four machine learning models based on data for change scores (baseline to twelve months) on the 59 neurocognitive measures and measures of depression, anxiety, and fatigue to determine a set of variables that distinguished the 24-month persistent cognitive decline group from non-cancer controls or from survivors without decline. RESULTS: The sample of survivors and controls ranged in age from were ages 60-89. Thirty-three percent of survivors had self-reported cognitive decline at twelve months and two-thirds continued to have persistent decline to 24 months (n = 60). Least Absolute Shrinkage and Selection Operator (LASSO) models distinguished survivors with persistent self-reported declines from controls (AUC = 0.736) and survivors without decline (n = 147; AUC = 0.744). The variables that separated groups were predominantly neurocognitive test performance change scores, including declines in list learning, verbal fluency, and attention measures. DISCUSSION: Machine learning may be useful to further our understanding of cancer-related cognitive decline. Our results suggest that persistent self-reported cognitive problems among older women with breast cancer are associated with a constellation of mild neurocognitive changes warranting clinical attention.

Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study.

PURPOSE: Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of cognition prior to adjuvant therapy and tumor aggressivity in older breast cancer patients. METHODS: Women diagnosed with non-metastatic breast cancer (n = 705) ages 60-98 were enrolled from August 2010-March 2020. Cognition was measured post-surgery, pre-systemic therapy using self-reported (FACT-Cog Perceived Cognitive Impairment [PCI]) and objective tests of attention, processing speed, and executive function (APE domain) and learning and memory [LM domain]. Linear regression tested associations of pre-treatment tumor features and cognition, adjusting for age, race, and study site. HER2 positivity and higher stage (II/III vs. 0/I) were a priori predictors of cognition; in secondary analyses we explored associations of other tumor features and cognitive impairment (i.e., PCI score < 54 or having 2 tests < 1.5 SD or 1 test < 2 SD from the mean APE or LM domain score). RESULTS: HER2 positivity and the hormone receptor negative/HER2 + molecular subtype were associated with lower adjusted mean self-reported cognition scores and higher impairment rates (p values < .05). Higher stage of disease was associated with lower objective performance in APE. Other tumor features were associated with cognition in unadjusted and adjusted models, including larger tumor size and lower PCI scores (p = 0.02). Tumor features were not related to LM. CONCLUSIONS: Pre-adjuvant therapy cognition was associated with HER2 positivity and higher stage of disease and other features of aggressive tumors. Additional research is needed to confirm these results and assess potential mechanisms and clinical management strategies.

Associations between longitudinal changes in sleep disturbance and depressive and anxiety symptoms during the COVID-19 virus pandemic among older women with and without breast cancer in the thinking and living with breast cancer study.

PURPOSE: Several studies have reported sleep disturbances during the COVID-19 virus pandemic. Little data exist about the impact of the pandemic on sleep and mental health among older women with breast cancer. We sought to examine whether women with and without breast cancer who experienced new sleep problems during the pandemic had worsening depression and anxiety. METHODS: Breast cancer survivors aged ≥60 years with a history of nonmetastatic breast cancer (n = 242) and frequency-matched noncancer controls (n = 158) active in a longitudinal cohort study completed a COVID-19 virus pandemic survey from May to September 2020 (response rate 83%). Incident sleep disturbance was measured using the restless sleep item from the Center for Epidemiological Studies-Depression Scale (CES-D). CES-D score (minus the sleep item) captured depressive symptoms; the State-Anxiety subscale of the State Trait Anxiety Inventory measured anxiety symptoms. Multivariable linear regression models examined how the development of sleep disturbance affected changes in depressive or anxiety symptoms from the most recent prepandemic survey to the pandemic survey, controlling for covariates. RESULTS: The prevalence of sleep disturbance during the pandemic was 22.3%, with incident sleep disturbance in 10% and 13.5% of survivors and controls, respectively. Depressive and anxiety symptoms significantly increased during the pandemic among women with incident sleep disturbance (vs. no disturbance) (ß = 8.16, p < 0.01 and ß = 6.14, p < 0.01, respectively), but there were no survivor-control differences in the effect. CONCLUSION: Development of sleep disturbances during the COVID-19 virus pandemic may negatively affect older women's mental health, but breast cancer survivors diagnosed with the nonmetastatic disease had similar experiences as women without cancer.

Hematologic safety of palbociclib in combination with endocrine therapy in patients with benign ethnic neutropenia and advanced breast cancer.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, are approved to treat hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) and are associated with hematologic toxicity. African American women, who are underrepresented in CDK4/6 inhibitor clinical trials, may experience worse neutropenia because of benign ethnic neutropenia. The authors specifically investigated the hematologic safety of palbociclib in African American women with HR-positive/HER2-negative ABC. METHODS: PALINA was a single-arm, open-label, investigator-initiated study of palbociclib (125 mg daily; 21 days on and 7 days off) plus endocrine therapy (ET) in African American women who had HR-positive/HER2-negative ABC and a baseline absolute neutrophil count ≥1000/mm3 (ClinicalTrials.gov identifier NCT02692755). The primary outcome was the proportion of patients who completed 12 months of therapy without experiencing febrile neutropenia or treatment discontinuation because of neutropenia. Single nucleotide polymorphism analysis was used to assess Duffy polymorphism status. RESULTS: Thirty-five patients received ≥1 dose of palbociclib plus ET; 19 had a Duffy null polymorphism (cytosine/cytosine). There were no reports of febrile neutropenia or permanent study discontinuation because of neutropenia. Significantly more patients with the Duffy null versus the wild-type variant had grade 3 and 4 neutropenia (72.2% vs 23.1%; P = .029) and required a palbociclib dose reduction (55.6% vs 7.7%; P = .008). Patients with the Duffy null versus the wild-type variant had lower overall relative dose intensity (mean ± SD, 81.89% ± 15.87 and 95.67% ± 5.89, respectively; P = .0026) and a lower clinical benefit rate (66.7% and 84.6%, respectively). CONCLUSIONS: These findings suggest that palbociclib is well tolerated in African American women with HR-positive/HER2-negative ABC. Duffy null status may affect the incidence of grade 3 neutropenia, dose intensity, and possibly clinical benefit.

Loneliness and mental health during the COVID-19 pandemic in older breast cancer survivors and noncancer controls.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had wide-ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. METHODS: The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web-based or telephone COVID-19 survey, between May 27 and September 11, 2020. Mixed-effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies-Depression [CES-D] scale) from before to during the pandemic in survivors versus controls and to test survivor-control differences in the associations between changes in loneliness and changes in mental health, including depression (CES-D, excluding the loneliness item), anxiety (the State-Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID-19 death rates, and time between assessments. RESULTS: Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor-control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor-control differences. CONCLUSIONS: Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic.

Does Scalp Cooling Have the Same Efficacy in Black Patients Receiving Chemotherapy for Breast Cancer?

LESSONS LEARNED: Despite U.S. Food and Drug Administration approval to reduce alopecia, data on efficacy of scalp cooling in Black patients with cancer are limited by lack of minority representation in prior clinical trials. Scalp cooling devices may have less efficacy in Black patients; additional studies are required to explore the possible causes for this, including hair texture and cap design. BACKGROUND: The Paxman scalp cooling (SC) device is U.S. Food and Drug Administration (FDA)-approved for prevention of chemotherapy-induced alopecia. Studies report 50%-80% success rates and high patient satisfaction, yet there have been no studies of SC in Black patients. We conducted a phase II feasibility study of Paxman SC with a planned enrollment of 30 Black patients receiving chemotherapy for stage I-III breast cancer. METHODS: Black patients who planned to receive at least four cycles of chemotherapy with non-anthracycline (NAC) or anthracycline (AC) regimens were eligible. Alopecia was assessed by trained oncology providers using the modified Dean scale (MDS) prior to each chemotherapy session. Distress related to alopecia was measured by the Chemotherapy Alopecia Distress Scale (CADS). RESULTS: Fifteen patients enrolled in the intervention before the study was closed early because of lack of efficacy. Median MDS and CADS increased after SC, suggesting increased hair loss (p < .001) and alopecia distress (p = .04). Only one participant was successful in preventing significant hair loss; the majority stopped SC before chemotherapy completion because of grade 3 alopecia (>50% hair loss). CONCLUSION: SC may not be efficacious in preventing alopecia in Black women. Differences in hair thickness, hair volume, and limitations of cooling cap design are possible contributing factors.

Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study.

BACKGROUND: Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS: The authors report on 36-month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS: All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P < .001). The burden score was related to physical, emotional, and functional well-being (eg, survivors with lower vs higher burden scores had 12.4-point higher physical well-being scores). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (P < .005). CONCLUSIONS: Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than in comparable noncancer populations, suggesting the need for surveillance and opportunities for intervention.

Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype.

BACKGROUND: Sleep disturbance and genetic profile are risks for cognitive decline in noncancer populations, yet their role in cancer-related cognitive problems remains understudied. This study examined whether sleep disturbance was associated with worse neurocognitive outcomes in breast cancer survivors and whether sleep effects on cognition varied by genotype. METHODS: Newly diagnosed female patients (n = 319) who were 60 years old or older and had stage 0 to III breast cancer were recruited from August 2010 to December 2015. Assessments were performed before systemic therapy and 12 and 24 months later. Neuropsychological testing measured attention, processing speed, executive function, learning, and memory; self-perceived cognitive functioning was also assessed. Sleep disturbance was defined by self-report of routine poor or restless sleep. Genotyping included APOE, BDNF, and COMT polymorphisms. Random effects fluctuation models tested associations of between-person and within-person differences in sleep, genotype, and sleep-genotype interactions and cognition and controlled for age, reading level, race, site, and treatment. RESULTS: One-third of the patients reported sleep disturbances at each time point. There was a sleep-APOE ε4 interaction (P = .001) in which patients with the APOE ε4 allele and sleep disturbances had significantly lower learning and memory scores than those who were APOE ε4-negative and without sleep disturbances. There was also a sleep disturbance-COMT genotype interaction (P = .02) in which COMT Val carriers with sleep disturbances had lower perceived cognition than noncarriers. CONCLUSIONS: Sleep disturbance was common and was associated with worse cognitive performance in older breast cancer survivors, especially those with a genetic risk for cognitive decline. Survivorship care should include sleep assessments and interventions to address sleep problems.

Providers' Perspectives on Adherence to Hormonal Therapy in Breast Cancer Survivors. Is there a Role for the Digital Health Feedback System?

OBJECTIVE: Despite the benefits of hormonal therapy (HT) adherence remains suboptimal in ER positive breast cancer patients. Medication adherence is challenging to assess and tends to be overestimated. The Digital Health Feedback System (DHFS) consists of an ingestible sensor attached to a pill that sends intake date and time to a smart phone or computer. Patients can share this information with health care providers and other persons. The DHFS can also send reminders. This mixed methods study examined providers' perceptions of HT medication adherence. The potential role of the DHFS in enhancing medication tracking and adherence was also explored. METHODS: We conducted semi-structured interviews with key informants (N=10). Questions examined perceptions about adherence barriers and facilitators, challenges tracking adherence, and views on the DHFS. Findings informed the development of a survey that was administered online (N=19). RESULTS: Providers emphasized the importance of fostering open and trustful communication around adherence. The most mentioned challenges to assessing adherence were the patient not disclosing discontinuation immediately (78.9%) and over-reporting adherence (57.9%). The perceived potential benefits of DHFS were the ability to track adherence better (94.7%) and reminders to take the medication (68.4%). Safety to ingest a sensor was as a major perceived barrier (8 4.2%). CONCLUSION: Interventions that target providers and doctor-patient communication are warranted to enhance adherence and reduce communication delays around HT discontinuation. PRACTICE IMPLICATIONS: DHFS has the potential to enhance HT adherence by directly targeting barriers. Future studies should also examine the feasibility of adopting the DHFS with cancer patients.

Pretreatment Psychoneurological Symptoms and Their Association With Longitudinal Cognitive Function and Quality of Life in Older Breast Cancer Survivors.

CONTEXT: Symptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied. OBJECTIVES: The objectives of this study were to identify prototypical presystemic therapy psychoneurological symptom clusters among older breast cancer survivors and determine whether these symptom clusters predicted cognition and QOL over time. METHODS: Women with newly diagnosed nonmetastatic breast cancer (n = 319) and matched noncancer controls (n = 347) aged 60+ years completed questionnaires and neuropsychological tests before systemic therapy and 12 and 24 months later. Latent class analysis identified clusters of survivors based on their pretherapy depression, anxiety, fatigue, sleep disturbance, and pain. Linear mixed-effects models examined changes in objective cognition, perceived cognition, and functional status (Instrumental Activities of Daily Living disability, functional well-being, and breast cancer-specific QOL) by group, controlling for covariates. RESULTS: Nearly one-fifth of older survivors were classified as having high pretherapy symptoms (n = 51; 16%); the remainder had low symptoms (n = 268; 84%); both groups improved over time on all outcomes. However, compared to the low symptom group and controls, survivors with high symptoms had lower baseline objective cognition and lower perceived cognition at baseline and 24 months, lower functional well-being at baseline and 12 months, greater Instrumental Activities of Daily Living disability at baseline, and lower breast cancer-specific QOL at all time points (all P < 0.05). CONCLUSION: Nearly one-fifth of older breast cancer survivors had high psychoneurological symptoms at diagnosis, which predicted clinically meaningful decrements in perceived cognition and function in the first 24 months after diagnosis. Pretreatment psychoneurological symptom clusters could identify survivors for monitoring or intervention.

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study.

PURPOSE: To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. METHODS: Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. RESULTS: Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores ( P = .05) and those initiating hormonal therapy having lower LM scores at 12 months ( P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant ( P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (-0.40; 95% CI, -0.79 to -0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures ( P < .001); frailty was associated with baseline APE and self-reported decline ( P < .001). CONCLUSION: Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning.

PALINA: A phase II safety study of palbociclib in combination with letrozole or fulvestrant in African American women with hormone receptor positive HER2 negative advanced breast cancer.

Palbociclib has been shown to be a highly effective therapy in hormone receptor positive metastatic breast cancer when used in combination with letrozole or fulvestrant. Grade 3/4 neutropenia is a common side effect although febrile neutropenia is relatively uncommon. Insufficient data exist to describe the hematological safety of palbociclib in African American women (AAW) known to have a high incidence of benign ethnic neutropenia (BEN). PALOMA 1, 2 and 3, the initial phase II/III studies that led to the U.S. Food and Drug Administration (FDA) approval of palbociclib in metastatic breast cancer, only included participants with baseline absolute neutrophil count (ANC) of 1500/mm3 or higher. African American women (AAW) were underrepresented in the PALOMA trials and this may be partially explained by strict requirements for minimal ANC ≥1500/mm3. The ANC of 1500/mm3 for initiation of treatment in those with BEN has been previously challenged. In this study, we propose to lower the ANC cutoff for enrollment to 1000/mm3. PALINA (NCT02692755) is a phase II, single arm, multicenter clinical trial that will enroll 35 patients. The primary endpoint is to assess the proportion of patients who complete therapy without the development of febrile neutropenia or treatment discontinuation due to neutropenia. The secondary endpoints include number of patients who required dose delays or dose reductions in palbociclib attributed to neutropenia, rate of grade 3/4 neutropenia, clinical benefit rate at 24 weeks, the association between metabolite and exosomal signature with disease response and the association between baseline ANC prior to cancer diagnosis and the Duffy Null polymorphism (SNP rs2814778) with hematological safety. PALINA will provide important information about the hematologic safety of palbociclib in AAW with advanced breast cancer.

Video intervention increases participation of black breast cancer patients in therapeutic trials.

There is a striking racial and ethnic disparity in incidence and mortality of cancer yet minorities remain markedly underrepresented in clinical trials. This pilot study set out to determine the impact of a 15-min culturally tailored educational video on three outcomes relating to clinical trials: likely participation, attitudes (assessed based on six barriers), and actual enrollment. Breast cancer patients with Stage I-III, if diagnosed within previous 6 months, or metastatic disease who self-identified as black or African American were invited to participate. The primary outcome measure was the decision to participate in a therapeutic clinical trial after the intervention. Patients' intention to enroll on a therapeutic clinical trial and the change in attitudes toward clinical trials were measured by the previously developed Attitudes and Intention to Enroll in Therapeutic Clinical Trials (AIET) questionnaire. Of the 200 patients that participated, 39 (19.5%) patients signed consent to participate in a therapeutic clinical trial; 27 (13.5%) patients enrolled, resulting in a 7.5% increase from our baseline comparison of 6% clinical trial enrollment rate in black cancer patients (p < .001). Pre-test versus post-test assessment demonstrated the proportion of patients expressing likelihood to enroll in a therapeutic trial following the intervention increased by 14% (p < .001). Among 31 AIET items, 25 (81%) showed statistically significant and positive change post-intervention. The findings suggest the promising utility of a culturally tailored video intervention for improving black patients' attitudes regarding clinical trial participation and resultant enrollment. Future efforts should continue to target facilitators of population-specific recruitment, enrollment, and retention in therapeutic and non-therapeutic clinical trials.

Correlates of Triple Negative Breast Cancer and Chemotherapy Patterns in Black and White Women With Breast Cancer.

BACKGROUND: Triple negative breast cancer (TNBC) tumors are estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor-negative. TNBC is responsive to chemotherapy, but chemotherapy might be underused in some patient subgroups. The goal of the present study was to characterize the patterns of chemotherapy use (uptake and completion) in TNBC patients. PATIENTS AND METHODS: Women with primary invasive, nonmetastatic breast cancer were recruited in Washington, DC, and Detroit. Data were collected using a standardized telephone survey that captured sociocultural and health care process factors. Clinical data were abstracted from the medical records. We used χ2 tests to access the association between the receipt of chemotherapy use (initiation and completion) and categorical variables, and t tests were used for continuous variables. Logistic regression models were used to evaluate the factors associated with chemotherapy uptake. RESULTS: Women with TNBC (16% of sample) were more likely to be black than white (68% vs. 32%; P < .05). Among women with TNBC, 60% underwent chemotherapy. Chemotherapy uptake was greater for black than for white women (48.3% vs. 11.7%; P = .01) and in women without (vs. with) healthcare discrimination (35% vs. 25%; P = .04). In multivariable models, only race was associated with the receipt of chemotherapy. Black women were more likely to receive chemotherapy than were white women. The odds ratio of receiving chemotherapy by race was 4.1 (95% confidence interval, 1.3-13.1). Each 1-year increase in age was associated with a lower likelihood of chemotherapy completion (odds ratio, 0.9; 95% confidence interval, 0.826-0.981; P = .02). Women with at least some college were less likely to complete chemotherapy than were those with other education levels (P = .02). CONCLUSION: A substantial number of TNBC patients failed to receive and/or complete chemotherapy. Differences in chemotherapy uptake by race and sociocultural factors diminished in multivariable models but age and stage remained significant. Suboptimal treatment among women with TNBC could contribute to adverse outcomes. Future investigations are necessary to assess whether the noninitiation and/or noncompletion of chemotherapy is clinically warranted.

Patterns of 21-gene assay testing and chemotherapy use in black and white breast cancer patients.

BACKGROUND: In women with early stage, hormone receptor (HR)-positive (HR(+)) breast cancer, the 21-gene recurrence score (RS) assay quantifies recurrence risk and predicts chemotherapy responsiveness. Recent data suggest that not all women with early-stage, HR(+) disease receive this testing. We examined sociodemographic, clinical, and attitudinal factors associated with RS testing receipt and the RS testing effect on chemotherapy use in black and white patients. PATIENTS AND METHODS: Women with newly diagnosed invasive, nonmetastatic breast cancer were recruited and interviewed to collect sociocultural and health care process data; clinical data were collected from charts. Of the sample (n = 359), 270 had HR(+) disease. Primary analysis focused on those with HR(+) node-negative disease (n = 143); secondary analyses included node-positive women. Logistic regression models evaluated factors associated with receipt of RS testing and chemotherapy. RESULTS: Among women eligible for the 21-gene assay, 62 patients [43%] received RS testing. In multivariable analysis, older age (odds ratio, 1.04 per 1 year increase; 95% confidence interval, 1.01-1.08) was associated with RS testing after adjustment for covariates. Chemotherapy use was 23%. In multivariable analysis, positive attitudes about chemotherapy and greater risk of recurrence were associated with chemotherapy use (P < .05). CONCLUSION: Patterns of genomic testing might vary according to age. Efforts to understand factors associated with low testing rates will be important.