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BACKGROUND: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). METHODS: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ2 test. RESULTS: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). CONCLUSIONS: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy.
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Capecitabina , Medición de Resultados Informados por el Paciente , Calidad de Vida , Neoplasias de la Mama Triple Negativas , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Capecitabina/uso terapéutico , Capecitabina/efectos adversos , Quimioterapia Adyuvante/métodos , Neoplasia Residual , Platino (Metal)/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
Geographic location of a patient directly impacts access to care, including preventive screenings and early detection. Although there is a higher prevalence of the most common cancers in urban areas, mortality rates are higher in rural communities. Notably, indigenous communities residing on tribal lands often experience heightened access issues and environmental exposure to known and probable human carcinogens. The burdens associated with a cancer diagnosis can be exacerbated by various barriers to accessing quality care; however, there are emerging best practices to overcome these barriers. Understanding the interplay between geography and a patient's access to cancer care services is crucial for addressing existing disparities and ensuring equitable health care provision across regions. By leveraging innovative policy and practice solutions, communities can begin to close care gaps and establish bidirectional trust between patients and providers across the care continuum, which is necessary to enact meaningful reforms. To advance the conversation on geographic disparities and strategies that mitigate associated barriers to care, NCCN hosted the Policy Summit "Cancer Across Geography" on June 15, 2023, at the National Press Club in Washington, DC. Through keynote addresses and multistakeholder panel discussions, this hybrid event explored care imbalances across geography, recent policy and technology advancements, and current challenges associated with cancer care. This created a forum for a diverse group of attendees to thoughtfully discuss policies and practices to advance high-quality, effective, efficient, equitable, and accessible cancer care for all. Speakers and attendees featured multidisciplinary clinicians, epidemiologists, community oncologists, researchers, payers, patient advocates, industry, providers, policymakers, and leaders representing underserved communities, among others.
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Accesibilidad a los Servicios de Salud , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/epidemiología , Neoplasias/diagnóstico , Accesibilidad a los Servicios de Salud/normas , Disparidades en Atención de Salud , Política de Salud , GeografíaRESUMEN
BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in germline BRCA1 or BRCA2 (BRCA1/2) mutation-associated metastatic breast cancer. However, studies evaluating PARP inhibitors plus platinum-based chemotherapy in germline BRCA1/2-wildtype triple-negative breast cancer are scarce. A large proportion of germline BRCA1/2-wildtype triple-negative breast cancer shows homologous recombination deficiency (HRD), resulting in a BRCA-like phenotype that might render sensitivity to PARP inhibitors. The S1416 trial assessed the efficacy of cisplatin combined with the PARP inhibitor veliparib in three predefined groups of metastatic breast cancer: germline BRCA1/2-mutated, BRCA-like, and non-BRCA-like. METHODS: S1416 was a randomised, double-blind, placebo-controlled, phase 2 trial conducted at 154 community and academic clinical sites across the USA. Eligible patients aged 18 years or older had metastatic or recurrent triple-negative breast cancer or germline BRCA1/2-associated metastatic or recurrent breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to one line of chemotherapy for metastatic disease. Patients were randomly assigned (1:1) via the National Clinical Trials Network open interactive system with dynamic balancing on number of previous cytotoxic regimens for metastatic disease to receive intravenous cisplatin (75 mg/m2, day 1) combined with either veliparib or matching placebo (300 mg orally twice a day, days 1-14) on a 21-day cycle. Investigators, patients, and the sponsors were masked to treatment assignment; the study statisticians were unmasked. Central testing after ran domisation classified patients as having mutated or wildtype germline BRCA1/2. A biomarker panel established a priori was used to classify patients with wildtype germline BRCA1/2 into BRCA-like and non-BRCA-like phenotype groups, with BRCA-like status based on at least one of the biomarkers: genomic instability score (≥42), somatic BRCA1/2 mutations, BRCA1 promoter methylation, or non-BRCA1/2 homologous recombination repair germline mutations. The primary endpoint was investigator-assessed progression-free survival, analysed separately for the three predefined biomarker groups with a prespecified α value for each analysis. Efficacy analyses were done by intention to treat and included all eligible patients. Safety analyses of toxicities attributed to treatment included all patients who received at least one dose of veliparib or placebo. The study is ongoing and registered with ClinicalTrials.gov, NCT02595905. FINDINGS: Between July 7, 2016, and June 15, 2019, 335 patients were enrolled and randomly assigned. 320 patients (n=162 to cisplatin plus veliparib, all women; and n=158 to cisplatin plus placebo, 157 women and one man) were eligible for efficacy evaluation. 247 patients were classified into the three biomarker groups: germline BRCA1/2-mutated (n=37), BRCA-like (n=101), and non-BRCA-like (n=109). 73 patients could not be classified due to missing biomarker information. Median follow-up was 11·1 months (IQR 5·6-20·8). In the germline BRCA1/2-mutated group, median progression-free survival was 6·2 months (95% CI 2·3-9·2) in the cisplatin plus veliparib group and 6·4 months (4·3-8·2) in the cisplatin plus placebo group (HR 0·79 [95% CI 0·38-1·67]; log-rank p=0·54). In the BRCA-like group, median progression-free survival was 5·9 months (95% CI 4·3-7·8) in the cisplatin plus veliparib group versus 4·2 months (2·3-5·0) in the cisplatin plus placebo group (HR 0·57 [95% CI 0·37-0·88]; p=0·010). In the non-BRCA-like group, median progression-free survival was 4·0 months (95% CI 2·5-4·7) in the cisplatin plus veliparib group versus 3·0 months (2·2-4·4) in the cisplatin plus placebo group (HR 0·89 [95% CI 0·60-1·33]; p=0·57). The most common grade 3 or worse adverse events attributed to treatment were neutropenia (71 [46%] of 155 patients in the cisplatin plus veliparib group vs 29 [20%] of 147 in the cisplatin plus placebo group), leukopenia (42 [27%] vs 11 [7%]), anaemia (35 [23%] vs 12 [8%]), and thrombocytopenia (29 [19%] vs four [3%]). Serious adverse events attributed to treatment occurred in 48 (31%) patients in the cisplatin plus veliparib group and 53 (36%) patients in the cisplatin plus placebo group. Treatment-related adverse events led to death in one patient in the cisplatin plus veliparib group (sepsis) and one patient in the cisplatin plus placebo group (acute kidney injury due to cisplatin plus heart failure from previous doxorubicin exposure). INTERPRETATION: The addition of veliparib to cisplatin significantly improved progression-free survival in patients with BRCA-like metastatic triple-negative breast cancer, but not in patients with non-BRCA-like metastatic breast cancer. PARP inhibitors combined with platinum-based chemotherapy should be explored further in BRCA-like triple-negative breast cancer. FUNDING: National Cancer Institute and National Institute of General Medical Sciences (US National Institutes of Health); AbbVie; Myriad Genetics; the Biomarker, Imaging, and Quality of Life Studies Funding Program (awarded by the National Cancer Institute); and The University of Kansas Cancer Center.
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Antineoplásicos , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Cisplatino/efectos adversos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Calidad de Vida , Recurrencia Local de Neoplasia/patología , Antineoplásicos/efectos adversos , Mutación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Método Doble CiegoRESUMEN
PURPOSE: Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN. METHODS: Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy. RESULTS: Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21). CONCLUSIONS: The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN. TRIAL REGISTRATION: Number: NCT01821833.
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Dolor Agudo , Neoplasias de la Mama , Ácidos Grasos Omega-3 , Enfermedades del Sistema Nervioso Periférico , Humanos , Femenino , Paclitaxel , Neoplasias de la Mama/tratamiento farmacológico , Proyectos Piloto , Dolor Agudo/tratamiento farmacológico , Dolor Agudo/prevención & control , Dolor Agudo/inducido químicamente , Método Doble Ciego , Ácidos Grasos Omega-3/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamenteRESUMEN
PURPOSE: CompLEEment-1 (NCT02941926) is a single-arm, open-label, multicentre phase IIIb study investigating the safety and efficacy of ribociclib plus letrozole (RIB + LET) in a large, diverse cohort who have not received prior endocrine therapy (ET) for advanced disease. We present an exploratory analysis of male patients. METHODS: Eligible patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), who had no prior ET and ≤ 1 line of prior chemotherapy for advanced disease, received RIB + LET. Male patients also received goserelin or leuprolide. Primary endpoint was safety and tolerability; efficacy was a secondary endpoint. RESULTS: In total, 39/3246 patients were male. Baseline characteristics were similar to the overall population. Male patients experienced fewer treatment-related adverse events (AEs) and treatment-related serious AEs compared with the overall population; fewer male patients had treatment-related AEs leading to discontinuation, adjustment/interruption, or additional therapy. One male patient died as a result of a serious AE that was not considered to be treatment-related. The most common AE was neutropenia; the incidence of grade ≥ 3 neutropenia in males (41.0%) was lower than in the overall population (57.2%). Median follow-up was 25.4 months; median time to progression was not reached in males versus 27.1 months for the overall population. CONCLUSION: The clinical benefit and overall response rates in males were consistent with the overall population. This analysis demonstrates the safety and efficacy of ribociclib in a close-to-real-world setting, supporting the use of RIB + LET in male patients with HR+, HER2- ABC. TRIAL REGISTRATION NUMBER: NCT02941926 (Registered 2016).
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama Masculina , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama Masculina/tratamiento farmacológico , Humanos , Letrozol/uso terapéutico , Masculino , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Purinas , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
PURPOSE: The purpose of this study was to evaluate patient, oncologist and nurse perspectives on side effects and patient reported outcomes (PROs) with the question of how to optimize side effect management and PRO tools in this unique population. METHODS: This pilot study utilized a mixed method explanatory design. Patients receiving intravenous (IV) chemotherapy from June to August 2020 were surveyed about side effect burden and PRO system preferences. Providers and nurses (PN) completed complementary surveys. Semi-structured phone interviews were conducted among a subset of each group. RESULTS: Of 90 patient surveys collected; 51.1% minority, 35.6% rural, and 40.0% income < $30,000, 48% felt side effect management was a significant issue. All patients reported access to a communication device but 12.2% did not own a cell phone; 68% smart phone, 20% cell phone, 22% landline, 53% computer, and 39% tablet. Patients preferred a response to reported side effects within 0-3 h (73%) while only 29% of the 55 PN surveyed did (p < 0.0001). Interviews reinforced that side effect burden was a significant issue, the varied communication devices, and a PRO system could improve side effect management. CONCLUSION: In a non-White, rural and low-income patient population, 87.8% of patients reported owning a cell phone. Although all agreed side effect management was a prominent issue, expectations between patients and PN differed substantially. Qualitative data echoed the above and providing concrete suggestions to inform development of a PRO program and side effect mitigation strategies among a diverse patient population.
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Etnicidad , Neoplasias , Minorías Étnicas y Raciales , Humanos , Grupos Minoritarios , Neoplasias/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Proyectos PilotoRESUMEN
Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors.
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The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer, and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for millions of women with early-stage and advanced HER2-positive breast cancer. This review discusses the treatment of primary, nonmetastatic HER2-positive breast cancer in the adjuvant and neoadjuvant settings--settings in which tremendous progress has been made. Novel approaches, including the use of combinations of HER2-targeted therapies, are examined. Future challenges include refining such treatments, reducing toxicity in those who have low-risk disease, and simultaneously developing innovative therapies for patients who remain at high risk for relapse with existing treatment options.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Receptor ErbB-2/metabolismo , Quimioterapia Adyuvante , Femenino , Humanos , Terapia Molecular Dirigida , Terapia NeoadyuvanteRESUMEN
This mixed method study developed multiple question types to understand and measure women's perceived benefit from adjuvant endocrine therapy. We hypothesis that patients do not understand this benefit and sought to develop the questions needed to test this hypothesis and obtain initial patient estimates. From 8/2022 to 3/2023, qualitative interviews focused on assessing and modifying 9 initial varied question types asking about the overall survival (OS) benefit from adjuvant endocrine therapy. Subsequent focus groups modified and selected the optimal questions. Patients' self-assessment of their OS benefit was compared to their individualized PREDICT model results. Fifty-three patients completed the survey; 42% Hispanic, 30% rural, and 47% with income < $39,999 per year. Patients reported adequate health care literacy (61.5%) and average confidence about treatment and medication decisions 49.4 (95% CI 24.4-59.5). From the original 9 questions, 3 modified questions were ultimately found to capture patients' perception of this OS benefit, focusing on graphical and prose styles. Patients estimated an OS benefit of 42% compared to 4.4% calculated from the PREDICT model (p < 0.001). In this group with considerable representation from ethnic minority, rural and low-income patients, qualitative data showed that more than one modality of question type was needed to clearly capture patients' understanding of treatment benefit. Women with breast cancer significantly overestimated their 10-year OS benefit from adjuvant endocrine therapy compared to the PREDICT model.
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Neoplasias de la Mama , Humanos , Femenino , Proyectos Piloto , Neoplasias de la Mama/tratamiento farmacológico , Etnicidad , Grupos Minoritarios , Terapia CombinadaRESUMEN
BACKGROUND: Provision of nutrition care for patients with cancer represents a key component of holistic oncology care. However, information is limited about the use and perceptions of registered dietitian-led nutrition care in the oncology setting. OBJECTIVES: This study aimed to better understand the experiences and expectations of patients and healthcare workers regarding nutrition care during outpatient cancer treatment. METHODS: Oncology care team members (N = 55) and patients (N = 90) completed a survey about their knowledge of and interest in nutrition care. A subset of participants completed semistructured interviews to capture experiences with and perspectives on nutrition care practices. FINDINGS: The majority of patients (n = 73) reported experiencing at least one nutrition impact symptom, but only 14 indicated that they frequently discussed nutrition during provider visits. In addition, 40 oncology care team members indicated frequently discussing nutrition at visits, although 13 were unaware of local nutrition resources.
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Personal de Salud , Neoplasias , Humanos , Actitud del Personal de Salud , Neoplasias/terapia , Encuestas y CuestionariosRESUMEN
Purpose: This mixed methods study developed multiple question types to understand and measure women's perceived benefit from adjuvant endocrine therapy. We hypothesis that patients do not understand this benefit and sought to develop the questions needed to test this hypothesis and obtain initial patient estimates. Methods: From 8/2022 to 3/2023, qualitative interviews focused on assessing and modifying 9 initial varied question types asking about the overall survival (OS) benefit from adjuvant endocrine therapy. Subsequent focus groups modified and selected the optimal questions. Patients' self-assessment of their OS benefit was compared to their individualized PREDICT model results. Results: Fifty-three patients completed the survey; 42% Hispanic, 30% rural, and 47% with income <$39,999 per year. Patients reported adequate health care literacy (61.5%) and average confidence about treatment and medication decisions 49.4 (95% CI 24.4-59.5). From the original 9 questions, 3 modified questions were ultimately found to capture patients' perception of this OS benefit, focusing on graphical and prose styles. Patients estimated an OS benefit of 42% compared to 4.4% calculated from the PREDICT model (p < 0.001). Conclusion: In this group with considerable representation from ethnic minority, rural and low-income patients, qualitative data showed that more than one modality of question type was needed to clearly capture patients' understanding of treatment benefit. Women with breast cancer significantly overestimated their 10-year OS benefit from adjuvant endocrine therapy compared to the PREDICT model.
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PURPOSE: To overcome resistance to antihormonal and HER2-targeted agents mediated by cyclin D1-CDK4/6 complex, we proposed an oral combination of the HER2 inhibitor tucatinib, aromatase inhibitor letrozole, and CDK4/6 inhibitor palbociclib (TLP combination) for treatment of HR+/HER2+ metastatic breast cancer (MBC). PATIENTS AND METHODS: Phase Ib/II TLP trial (NCT03054363) enrolled patients with HR+/HER2+ MBC treated with ≥2 HER2-targeted agents. The phase Ib primary endpoint was safety of the regimen evaluated by NCI CTCAE version 4.3. The phase II primary endpoint was efficacy by median progression-free survival (mPFS). RESULTS: Forty-two women ages 22 to 81 years were enrolled. Patients received a median of two lines of therapy in the metastatic setting, 71.4% had visceral disease, 35.7% had CNS disease. The most common treatment-emergent adverse events (AE) of grade ≥3 were neutropenia (64.3%), leukopenia (23.8%), diarrhea (19.0%), and fatigue (14.3%). Tucatinib increased AUC10-19 hours of palbociclib 1.7-fold, requiring palbociclib dose reduction from 125 to 75 mg daily. In 40 response-evaluable patients, mPFS was 8.4 months, with similar mPFS in non-CNS and CNS cohorts (10.0 months vs. 8.2 months; P = 0.9). Overall response rate was 44.5%, median duration of response was 13.9 months, and clinical benefit rate was 70.4%; 60% of patients were on treatment for ≥6 months, 25% for ≥1 year, and 10% for ≥2 years. In the CNS cohort, 26.6% of patients remained on study for ≥1 year. CONCLUSIONS: TLP combination was safe and tolerable. AEs were expected and manageable with supportive therapy and dose reductions. TLP showed excellent efficacy for an all-oral chemotherapy-free regimen warranting further testing. See related commentary by Huppert and Rugo, p. 4993.
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Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Letrozol , Neoplasias de la Mama/patología , Receptor ErbB-2/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antineoplásicos/uso terapéuticoRESUMEN
PURPOSE: Primary prophylactic colony-stimulating factors (PP-CSFs) are prescribed to reduce febrile neutropenia (FN) but their benefit for intermediate FN risk regimens is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) PP-CSF intervention, we conducted a substudy to evaluate the effectiveness of SOE for patients receiving intermediate-risk regimens. METHODS: TrACER was a cluster randomized trial where practices were randomized to usual care or a guideline-based SOE intervention. In the primary study, sites were randomized 3:1 to SOE of automated PP-CSF orders for high FN risk regimens and alerts against PP-CSF use for low-risk regimens versus usual care. A secondary 1:1 randomization assigned 24 intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for intermediate-risk regimens. Clinicians were allowed to over-ride the SOE. Patients with breast, colorectal, or non-small-cell lung cancer were enrolled. Mixed-effect logistic regression models were used to test differences between randomized sites. RESULTS: Between January 2016 and April 2020, 846 eligible patients receiving intermediate-risk regimens were registered to either SOE to prescribe (12 sites: n = 542) or an alert to not prescribe PP-CSF (12 sites: n = 304). Rates of PP-CSF use were higher among sites randomized to SOE (37.1% v 9.9%, odds ratio, 5.91; 95% CI, 1.77 to 19.70; P = .0038). Rates of FN were low and identical between arms (3.7% v 3.7%). CONCLUSION: Although implementation of a SOE intervention for PP-CSF significantly increased PP-CSF use among patients receiving first-line intermediate-risk regimens, FN rates were low and did not differ between arms. Although this guideline-informed SOE influenced prescribing, the results suggest that neither SOE nor PP-CSF provides sufficient benefit to justify their use for all patients receiving first-line intermediate-risk regimens.
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Neoplasias de la Mama , Carcinoma de Pulmón de Células no Pequeñas , Neutropenia Febril , Neoplasias Pulmonares , Órdenes Permanentes , Humanos , Femenino , Factores Estimulantes de Colonias/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/etiología , Neutropenia Febril/inducido químicamente , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/prevención & control , Neoplasias Pulmonares/tratamiento farmacológico , Modelos Logísticos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/etiologíaRESUMEN
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted.
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Neoplasias de la Mama , Humanos , Femenino , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Receptor ErbB-2 , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
OBJECTIVES: To assess the efficacy of the University of New Mexico Comprehensive Cancer Center's (UNMCCC's) breast cancer nurse navigator (BCNN) program in addressing gaps in cancer care for an underserved, rural, and economically disadvantaged population. SAMPLE & SETTING: 54 navigated patients under the care of the BCNN and 32 non-navigated patients whose care began prior to the start of the program. METHODS & VARIABLES: Surveys were administered anonymously to patients during regularly scheduled appointments at UNMCCC. RESULTS: Navigated patients more strongly agreed that they were prepared for the beginning of treatment and that calls were returned promptly, and showed a decreased desire for an after-treatment summary compared to non-navigated patients. IMPLICATIONS FOR NURSING: Navigated patients report better understanding of and engagement with the healthcare system when assisted by a BCNN during breast cancer treatment with curative intent, as well as desire fewer services than non-navigated peers, indicating greater satisfaction.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/terapia , Medición de Resultados Informados por el Paciente , Encuestas y Cuestionarios , Poblaciones VulnerablesRESUMEN
Importance: Colony-stimulating factors are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia. Research suggests that 55% to 95% of colony-stimulating factor prescribing is inconsistent with national guidelines. Objective: To examine whether a guideline-based standing order for primary prophylactic colony-stimulating factors improves use and reduces the incidence of febrile neutropenia. Design, Setting, and Participants: This cluster randomized clinical trial, the Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER), involved 32 community oncology clinics in the US. Participants were adult patients with breast, colorectal, or non-small cell lung cancer initiating cancer therapy and enrolled between January 2016 and April 2020. Data analysis was performed from July to October 2021. Interventions: Sites were randomized 3:1 to implementation of a guideline-based primary prophylactic colony-stimulating factor standing order system or usual care. Automated orders were added for high-risk regimens, and an alert not to prescribe was included for low-risk regimens. Risk was based on National Comprehensive Cancer Network guidelines. Main Outcomes and Measures: The primary outcome was to find an increase in colony-stimulating factor use among high-risk patients from 40% to 75%, a reduction in use among low-risk patients from 17% to 7%, and a 50% reduction in febrile neutropenia rates in the intervention group. Mixed model logistic regression adjusted for correlation of outcomes within a clinic. Results: A total of 2946 patients (median [IQR] age, 59.0 [50.0-67.0] years; 2233 women [77.0%]; 2292 White [79.1%]) were enrolled; 2287 were randomized to the intervention, and 659 were randomized to usual care. Colony-stimulating factor use for patients receiving high-risk regimens was high and not significantly different between groups (847 of 950 patients [89.2%] in the intervention group vs 296 of 309 patients [95.8%] in the usual care group). Among high-risk patients, febrile neutropenia rates for the intervention (58 of 947 patients [6.1%]) and usual care (13 of 308 patients [4.2%]) groups were not significantly different. The febrile neutropenia rate for patients receiving high-risk regimens not receiving colony-stimulating factors was 14.9% (17 of 114 patients). Among the 585 patients receiving low-risk regimens, colony-stimulating factor use was low and did not differ between groups (29 of 457 patients [6.3%] in the intervention group vs 7 of 128 patients [5.5%] in the usual care group). Febrile neutropenia rates did not differ between usual care (1 of 127 patients [0.8%]) and the intervention (7 of 452 patients [1.5%]) groups. Conclusions and Relevance: In this cluster randomized clinical trial, implementation of a guideline-informed standing order did not affect colony-stimulating factor use or febrile neutropenia rates in high-risk and low-risk patients. Overall, use was generally appropriate for the level of risk. Standing order interventions do not appear to be necessary or effective in the setting of prophylactic colony-stimulating factor prescribing. Trial Registration: ClinicalTrials.gov Identifier: NCT02728596.
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Factores Estimulantes de Colonias , Sistemas de Apoyo a Decisiones Clínicas , Neutropenia Febril , Neoplasias , Adulto , Femenino , Humanos , Persona de Mediana Edad , Factores Estimulantes de Colonias/uso terapéutico , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/prevención & control , Neoplasias/tratamiento farmacológico , AncianoRESUMEN
INTRODUCTION: Neoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC. METHODS: We conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m2 IV weekly ×12 followed by doxorubicin 24 mg/m2 IV weekly + cyclophosphamide 60 mg/m2 PO daily with G-CSF support. Response was evaluated using pCR in the breast and the CPS + EG score (clinical-pathologic scoring + estrogen receptor [ER] and grade). RESULTS: Seventy patients enrolled, and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER+ disease and 8 had triple-negative disease). When defining response as pCR and/or CPS + EG score ≤2, 31 (47%) were responders. In pateints with ER positive disease, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue. CONCLUSIONS: Neoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR; however, 47% were responders using pCR and/or CPS + EG score ≤2. ER positive patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for patients with ER positive LABC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Inflamatorias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Sunitinib/uso terapéutico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Inflamatorias de la Mama/patología , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Fatal metastasis occurs when circulating tumor cells (CTCs) disperse through the blood to initiate a new tumor at specific sites distant from the primary tumor. CTCs have been classically defined as nucleated cells positive for epithelial cell adhesion molecule and select cytokeratins (EpCAM/CK/DAPI), while negative for the common lymphocyte marker CD45. The enumeration of CTCs allows an estimation of the overall metastatic burden in breast cancer patients, but challenges regarding CTC heterogeneity and metastatic propensities persist, and their decryption could improve therapies. CTCs from metastatic breast cancer (mBC) patients were captured using the RareCyteTM Cytefinder II platform. The Lin- and Lin+ (CD45+) cell populations isolated from the blood of three of these mBC patients were analyzed by single-cell transcriptomic methods, which identified a variety of immune cell populations and a cluster of cells with a distinct gene expression signature, which includes both cells expressing EpCAM/CK ("classic" CTCs) and cells possessing an array of genes not previously associated with CTCs. This study put forward notions that the identification of these genes and their interactions will promote novel areas of analysis by dissecting properties underlying CTC survival, proliferation, and interaction with circulatory immune cells. It improves upon capabilities to measure and interfere with CTCs for impactful therapeutic interventions.
RESUMEN
Harvest for Health is a home-based vegetable gardening intervention that pairs cancer survivors with Master Gardeners from the Cooperative Extension System. Initially developed and tested in Alabama, the program was adapted for the different climate, growing conditions, and population in New Mexico. This paper chronicles the feasibility, acceptability, and preliminary efficacy of "Southwest Harvest for Health". During the nine-month single-arm trial, 30 cancer survivor-Master Gardener dyads worked together to establish and maintain three seasonal gardens. Primary outcomes were accrual, retention, and satisfaction. Secondary outcomes were vegetable and fruit (V and F) intake, physical activity, and quality of life. Recruitment was diverse and robust, with 30 survivors of various cancers, aged 50-83, roughly one-third minority, and two-thirds females enrolled in just 60 days. Despite challenges due to the COVID-19 pandemic, retention to the nine-month study was 100%, 93% reported "good-to-excellent" satisfaction, and 87% "would do it again." A median increase of 1.2 servings of V and F/day was documented. The adapted home-based vegetable gardening program was feasible, well-received, and resulted in increased V and F consumption among adult cancer survivors. Future studies are needed to evaluate the effectiveness of this program and to inform strategies to increase the successful implementation and further dissemination of this intervention.
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Supervivientes de Cáncer/educación , Jardinería/educación , Terapia Hortícola/métodos , Mentores , Verduras , Anciano , Anciano de 80 o más Años , Supervivientes de Cáncer/psicología , Dieta Saludable/estadística & datos numéricos , Ejercicio Físico , Femenino , Estilo de Vida Saludable , Terapia Hortícola/psicología , Humanos , Masculino , Persona de Mediana Edad , New Mexico , Proyectos Piloto , Calidad de VidaRESUMEN
Few diet and physical activity evidence-based interventions have been routinely used in community settings to achieve population health outcomes. Adapting interventions to fit the implementation context is important to achieve the desired results. Harvest for Health is a home-based vegetable gardening intervention that pairs cancer survivors with certified Master Gardeners from the Cooperative Extension Service with the ultimate goal of increasing vegetable consumption and physical activity, and improving physical functioning and health-related quality-of-life. Harvest for Health has potential for widespread dissemination since Master Gardener Programs exist throughout the United States. However, state- and population-specific adaptations may be needed to improve intervention adoption by other Master Gardener Programs. Our primary objective was to adapt this evidence-informed intervention that was initially incepted in Alabama, for the drastically different climate and growing conditions of New Mexico using a recommended adaptation framework. Our secondary objective was to develop a study protocol to support a pilot test of the adapted intervention, Southwest Harvest for Health. The adaptation phase is a critical first step towards widespread dissemination, implementation, and scale-out of an evidence-based intervention. This paper describes the adaptation process and outcomes, and the resulting protocol for the ongoing pilot study that is currently following 30 cancer survivors and their paired Extension Master Gardener mentors.