Oncologist Perceptions of Racial Disparity, Racial Anxiety, and Unconscious Bias in Clinical Interactions, Treatment, and Outcomes.

BACKGROUND: Cancer spares no demographic or socioeconomic group; it is indeed the great equalizer. But its distribution is not equal; when structural discrimination concentrates poverty and race, zip code surpasses genetic code in predicting outcomes. Compared with White patients in the United States, Black patients are less likely to receive appropriate treatment and referral to clinical trials, genetic testing, or palliative care/hospice. METHODS: In 2021, we administered a survey to 369 oncologists measuring differences in perceptions surrounding racial disparity, racial anxiety, and unconscious bias and adverse influence on clinical interactions, treatment, and outcomes for non-White patients. We analyzed responses by generational age group, sex/gender, race/ethnicity, US region, and selection of "decline to respond." RESULTS: The most significant differences occurred by age group followed by race/ethnicity. Racial disparity was perceived as moderate to very high by 84% of millennial, 69% of Generation X, and 57% of baby boomer oncologists, who were also 86% more likely than millennials and 63% more likely than Generation Xers to perceive low/nonexistent levels of racial anxiety/unconscious bias. CONCLUSIONS: Most oncologists rarely or never perceived racial anxiety/unconscious bias as adversely influencing clinical treatment or survival outcomes in non-White patients, and White oncologists were 85% more likely than non-White oncologists to perceive rare/nonexistent influence on referral of non-White patients to palliative care/hospice. The discrepancy between 62% of oncologists perceiving moderate to very high levels of racial anxiety/unconscious bias and 37% associating them with adverse influence on non-White patients shows a disconnect, especially among older oncologists (baby boomers), who were also least likely to select the decline option. Together, these factors hinder effective patient-provider communication and result in differential care and outcomes. Oncologists should uncover their own perceptions surrounding racial disparity, racial anxiety, and unconscious bias and modify their behaviors accordingly. It is this simple-and this complicated. Cancer does not discriminate, and neither should cancer care.

Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices.

BACKGROUND: The treatment landscape for advanced hepatocellular carcinoma (aHCC) is rapidly expanding beyond tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting, with multiple TKIs and immune-checkpoint inhibitors (ICIs) now being evaluated in combination. Real-world evidence describing current treatment patterns and reasons for 1L and 2L treatment selection in aHCC is sparse. PATIENTS AND METHODS: A retrospective cohort study with a cross-sectional survey element was conducted using Cardinal Health's Oncology Provider Extended Network. U.S. medical oncologists identified adult aHCC patients initiating 1L systemic therapy between January 1, 2017 and July 31, 2019 and abstracted data from patient medical records. Data included provider characteristics, patient demographics and clinical characteristics, treatment regimens, and physician rationale for treatment regimen choice. RESULTS: A total of 44 medical oncologists provided data on 284 aHCC patients. The median age at 1L initiation was 61.5 years, and the majority were male (78%) and white (66%). Nearly half (47%) initiated 1L treatment in 2019, 34% were ECOG performance status 2+, and 63% were Child-Pugh Class B/C. Among the 284 aHCC patients, TKIs were used by 94% of patients in the 1L setting, comprised predominantly of sorafenib (54%) and lenvatinib (38%). ICIs were most common among the 90 patients (66%) who received 2L treatment. CONCLUSION: In the community-oncology practice setting, nearly all aHCC patients received sorafenib or lenvatinib in the 1L setting, while the majority of patients received an ICI in the 2L setting. With recent ICI approvals in aHCC, this marks the beginning of an increased use of ICIs in the 1L setting.

Complement activation and regulation in preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome.

The complement system is critical to human health owing to its central role in host defense and innate immunity. During pregnancy, the complement system must be appropriately regulated to allow for immunologic tolerance to the developing fetus and placenta. Although some degree of complement activation can be seen in normal pregnancy, the fetus seems to be protected in part through the placental expression of complement regulatory proteins, which inhibit complement activation at different steps along the complement activation cascade. In women who develop preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, there is a shift toward increased complement activation and decreased complement regulation. There is an increase in placental deposition of C5b-9, which is the terminal effector of classical, lectin, and alternative complement pathways. C5b-9 deposition stimulates trophoblasts to secrete soluble fms-like tyrosine kinase-1, which sequesters vascular endothelial growth factor and placental growth factor. Pathogenic mutations or deletions in complement regulatory genes, which predispose to increased complement activation, have been detected in women with preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Before the disease, biomarkers of alternative complement pathway activation are increased; during active disease, biomarkers of terminal complement pathway activation are increased. Urinary excretion of C5b-9 is associated with preeclampsia with severe features and distinguishes it from other hypertensive disorders of pregnancy. Taken together, existing data link preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome with increased activation of the terminal complement pathway that, in some cases, may be influenced by genetic alterations in complement regulators. These findings suggest that the inhibition of the terminal complement pathway, possibly through C5 blockade, may be an effective strategy to treat preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, but this strategy warrants further evaluation in clinical trials.

Clinical and Demographic Risk Factors for COVID-19 during Delivery Hospitalizations in New York City.

OBJECTIVE: This study was aimed to review 4 weeks of universal novel coronavirus disease 2019 (COVID-19) screening among delivery hospitalizations, at two hospitals in March and April 2020 in New York City, to compare outcomes between patients based on COVID-19 status and to determine whether demographic risk factors and symptoms predicted screening positive for COVID-19. STUDY DESIGN: This retrospective cohort study evaluated all patients admitted for delivery from March 22 to April 18, 2020, at two New York City hospitals. Obstetrical and neonatal outcomes were collected. The relationship between COVID-19 and demographic, clinical, and maternal and neonatal outcome data was evaluated. Demographic data included the number of COVID-19 cases ascertained by ZIP code of residence. Adjusted logistic regression models were performed to determine predictability of demographic risk factors for COVID-19. RESULTS: Of 454 women delivered, 79 (17%) had COVID-19. Of those, 27.9% (n = 22) had symptoms such as cough (13.9%), fever (10.1%), chest pain (5.1%), and myalgia (5.1%). While women with COVID-19 were more likely to live in the ZIP codes quartile with the most cases (47 vs. 41%) and less likely to live in the ZIP code quartile with the fewest cases (6 vs. 14%), these comparisons were not statistically significant (p = 0.18). Women with COVID-19 were less likely to have a vaginal delivery (55.2 vs. 51.9%, p = 0.04) and had a significantly longer postpartum length of stay with cesarean (2.00 vs. 2.67days, p < 0.01). COVID-19 was associated with higher risk for diagnoses of chorioamnionitis and pneumonia and fevers without a focal diagnosis. In adjusted analyses, including demographic factors, logistic regression demonstrated a c-statistic of 0.71 (95% confidence interval [CI]: 0.69, 0.80). CONCLUSION: COVID-19 symptoms were present in a minority of COVID-19-positive women admitted for delivery. Significant differences in obstetrical outcomes were found. While demographic risk factors demonstrated acceptable discrimination, risk prediction does not capture a significant portion of COVID-19-positive patients. KEY POINTS: · COVID-19 symptoms were present in a minority of COVID-19-positive women admitted.. · COVID-19 symptomatology did not appear to differ before or after the apex of infection in New York.. · Demographic risk factors are unlikely to capture a significant portion of COVID-19-positive patients..

Comparative Effectiveness of Palliative Chemotherapy in Metastatic Breast Cancer: A Real-World Evidence Analysis.

BACKGROUND: In the absence of randomized controlled trials, real-world evidence may aid practitioners in optimizing the selection of therapy for patients with cancer. The study's aim was to determine real-word use, as well as compare effectiveness, of single-agent and combination chemotherapy as palliative treatment for female patients with metastatic breast cancer (mBC). MATERIALS AND METHODS: Using administrative claims data from the Symphony Health's Integrated Oncology Dataverse, female patients with mBC treated with at least one chemotherapy-only treatment (COT) between January 1, 2013, and December 31, 2017 were selected. The frequency of use of single-agent versus combination chemotherapy overall and by line of therapy (LOT) was calculated whereas effectiveness was measured using time to next treatment (TNT). RESULTS: A total of 12,381 patients with mBC were identified, and 3,777 (31%) received at least one line of COT. Of the 5,586 observed LOTs among the 3,777 patients, 66.5% were single-agent and 33.5% combination chemotherapy. Combination chemotherapy was most frequently used in first-line (45%) and least frequently in fifth-line (16%). Across all LOTs, median TNT was significantly longer for single-agent versus combination chemotherapy (5.3 months vs. 4.1 months, p < .0001). Comparison of median TNT by LOT showed significance in third-line and greater but not in first-line or second-line. Among single agents, the median TNT for patients receiving capecitabine was longest in comparison to all other single agents. CONCLUSIONS: The frequency of combination COT use, particularly in first-line, warrants further research given published guideline recommendations. The observed TNT difference favoring single-agent treatment in later lines supports guideline recommendations. Variance between single-agent preference and observed TNT was noteworthy. IMPLICATIONS FOR PRACTICE: Although published data from evidence- and consensus-based guidelines recommend single-agent over combination chemotherapy, the extensive list of agents available for use and a gap in the comparative effectiveness research of these agents have resulted in significant variances in patterns of care. The aim of this study was to assess real-world treatment patterns and their effectiveness during palliative therapy of metastatic breast cancer. The objective was to understand when and how chemotherapy-only treatment is used in metastatic breast cancer and whether comparative effectiveness analysis supports the observed patterns of care.

Use of Real-World Evidence to Support FDA Approval of Oncology Drugs.

OBJECTIVES: Real-world evidence (RWE) has gained increased attention in recent years as a complement to traditional clinical trials. The use of RWE to establish the efficacy of oncology drugs for Food and Drug Administration (FDA) approval has not been described. In this paper, we review 5 recent examples where RWE was submitted in support of the FDA approvals of original or supplementary indications for oncology drugs. METHODS: To identify cases where RWE was used, we reviewed drug approval packages available at Drugs@FDA for oncology drugs approved between 2017 and 2019. Five cases were selected to present a broad overview of different types of RWE, different circumstances under which RWE has been used for regulatory approvals, and how FDA evaluated the data in each case. The type of RWE submitted, the indication, limitations identified by FDA reviewers, and the outcome of the submission are discussed. RESULTS: RWE, particularly historical controls for rare or orphan indications, has been used to support both original and supplementary oncology drug approvals. Types of RWE included data from electronic health records, claims, post-marketing safety reports, retrospective medical record reviews, and expanded access studies. Small sample sizes, data quality, and methodological issues were among concerns cited by FDA reviewers. CONCLUSION: By bridging the gap between the constraints of the trial setting and the realities of clinical practice, RWE can add value to a regulatory submission. These early examples provide insight into how regulators evaluated RWE submitted as evidence of efficacy for oncology drugs.

Making the case for EGFR TKI sequencing in EGFR mutation-positive NSCLC: a GioTag study US patient analysis.

Aim: To assess time-to-treatment failure (TTF) in US patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib-osimertinib treatment in the global, observational GioTag study. Patients & methods: Patients had EGFR T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. Results: In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0-34.1). Median overall survival was 47.6 months (90% CI: 35.5-51.5). Conclusion: Sequential afatinib-osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov).

Physician treatment of metastatic triple-negative breast cancer in the immuno-oncology era: a discrete choice experiment.

Aim: Guidelines list atezolizumab with nab-paclitaxel (ANP) as the preferred first-line (1L) therapy for metastatic triple-negative breast cancer (mTNBC) with PD-L1 expression ≥1%, but which clinical attributes impact ANP prescribing? Materials & methods: Medical oncologists participated in a discrete choice experiment (DCE) with four hypothetical mTNBC clinical scenarios to assess influences of: PD-L1 expression, menopausal status, prior adjuvant therapy and bulky liver metastases. Results: A total of 47% chose ANP in 1L irrespective of menopausal status, prior adjuvant therapy or tumor bulk. PD-L1 expression was the only attribute with a significant impact on ANP preference, with 69% choosing ANP for those with ≥1% expression versus only 26% for those with <1% (p < 0.00001). Conclusion: ANP choice for 1L mTNBC deviated from guidelines.

Real-world incidence and cost of pneumonitis post-chemoradiotherapy for Stage III non-small-cell lung cancer.

Aim: To estimate the real-world incidence and timing of radiation pneumonitis following chemoradiotherapy for Stage III non-small-cell lung cancer and compare costs between patients with and without radiation pneumonitis. Methods: Retrospective analysis using the Symphony Health Integrated Dataverse. Results: Pneumonitis incidence was 12.4% with a 177-day mean time to onset. Patients with versus without pneumonitis were more frequently admitted to the hospital (33.8 vs 19.2%, p < 0.0001) and seen in the emergency room (51.9 vs 35.8%, p < 0.0001) and had higher mean total healthcare costs (US$4251 vs US$3969 per-patient per-month; p = 0.0163). Conclusion: Although pneumonitis significantly increased healthcare resource utilization and costs in chemoradiotherapy-treated Stage III non-small-cell lung cancer, the per-patient per-month differential was <10%. Such financial assessments are critical for cost-benefit analysis.

Patterns of Care Among Real-World Patients with Metastatic Neuroendocrine Tumors.

BACKGROUND: Although recent pivotal trials (PROMID, CLARINET) have established somatostatin analogs (SSAs) as first-line agents for neuroendocrine tumors (NETs), their use in clinical practice is largely unknown. We aimed to understand real-world management and treatment of gastroenteropancreatic (GEP) NETs. MATERIALS AND METHODS: Patients with metastatic GEP-NETs treated with SSAs, lanreotide depot or octreotide long-acting release (LAR), between January 1, 2015, and December 31, 2015, were identified from a U.S. claims database supplemented with chart review for a subset of patients. Descriptive statistics summarized patients' demographics, clinical characteristics, treatment patterns, and healthcare resource use. Univariate and multivariate comparisons were made across SSA groups. RESULTS: Among 548 patients treated with an SSA for metastatic GEP-NET (lanreotide = 108; octreotide = 440), demographic and clinical characteristics were similar across groups, except more patients with pancreatic NETs were treated with lanreotide (38.7% vs. 6.3%, p < .01). More octreotide patients had a diagnosis of carcinoid syndrome compared with lanreotide patients (19.8% vs. 11.1%, p = .02). Approximately 1.1% of patients received lanreotide (>120 mg every 4 weeks [Q4W]) at a dose above label compared with 12.7% of octreotide patients (>30 mg Q4W; p < .01). At 1.5 years after SSA initiation, 85.7% (95% confidence interval, 74.3%-92.3%) were still on index SSA as reported by the physician. Variances between chart review and claims data were significant. CONCLUSION: SSAs were common in first-line systemic intervention, but dose escalations and dosing deviations outside of label were noted. Variances between claims and chart review warrant additional research to compare methodologies. With an increasing focus on value-based care in oncology, it is critical to understand the use of, and outcomes with, these agents in community practices. IMPLICATIONS FOR PRACTICE: The aim of this study was to enhance understanding of real-world management and treatment of metastatic neuroendocrine tumors (NETs), with particular focus on systemic therapy with a somatostatin analog (SSA). As per published guidelines, SSAs are common in first-line systemic intervention, but dose escalations and dosing deviations outside of the label are noted for symptom control. Nevertheless, oncologists must weigh the implications of the use of above-label dosing of SSAs to manage and treat patients with metastatic NET within a value-based care framework.

Targeted agents or immuno-oncology therapies as first-line therapy for BRAF-mutated metastatic melanoma: a real-world study.

Aim: Targeted therapy (TT) and immuno-oncology (IO) drugs are approved for patients with BRAF mutant metastatic melanoma (MM). We compared real-world outcomes for first-line (1L) TT versus 1L IO to evaluate optimal sequencing. Materials & methods: Physicians-identified BRAF mutant MM patients initiating 1L TT or IO therapies and extracted treatment, disease and clinical outcomes including disease response which were compared between TT and IO and individual regimens. Results: 440 MM patients (TT = 283, IO = 157) were identified. A higher proportion of TT patients had liver metastases (46.3 vs 35.0%) and abnormal lactate dehydrogenase (61.1 vs 42.7%). IO-treated had a RECIST-determined response rate of 45.9 versus 60.1% for TT and time on treatment of 7.2 versus 11.4 months, respectively. There was no survival difference between cohorts. Conclusion: Despite higher risk patients, 1L TT resulted in higher response rate and longer treatment duration suggesting a preferred 1L sequence.

Observational study of clinical outcomes of eribulin mesylate in metastatic breast cancer after cyclin-dependent kinase 4/6 inhibitor therapy.

Aim: To examine the effectiveness of eribulin mesylate for metastatic breast cancer post cyclin-dependent kinase inhibitor (CDKi) 4/6 therapy. Materials & methods: US community oncologists reviewed charts of patients who had received eribulin from 3 February 2015 to 31 December 2017 after prior CDKi 4/6 therapy and detailed their clinical/treatment history, clinical outcomes (lesion measurements, progression, death) and toxicity. Results: Four patient cohorts were created according to eribulin line of therapy: second line, third line, per US label and fourth line with objective response rates/clinical benefit rates of 42.2%/58.7%, 26.1%/42.3%, 26.7%/54.1% and 17.9%/46.4%, respectively. Median progression-free survival/6-month progression-free survival (79.5% of all patients censored) by cohort was: 9.7 months/77.3%, 10.3 months/71.3%, not reached/70.4% and 4.0 months/0.0%, respectively. Overall occurrence of neutropenia = 23.5%, febrile neutropenia = 1.3%, peripheral neuropathy = 10.1% and diarrhea = 11.1%. Conclusion: Clinical outcome and adverse event rates were similar to those in clinical trials and other observational studies. Longer follow-up is required to confirm these findings.

Barriers to Oncology Biosimilars Uptake in the United States.

Biosimilars are biological compounds that contain an active substance that is similar to the active substance in an already approved biologic. This commentary focuses on the barriers to the use of biosimilars in the United States.

Using Response Evaluation Criteria in Solid Tumors in real-world evidence cancer research.

AIM: Real-world evidence of charted treatment responses to cancer drug therapy was compared with medical record derived radiographic measurements of target lesions per Response Evaluation Criteria in Solid Tumors (RECIST). MATERIALS & METHODS: 15 physicians treating 59 metastatic Merkel cell cancer (mMCC) patients contributed patient-level data. A comparison of medical record reported best response with radiographic measurements per RECIST of pre- and post-treatment target lesions. RESULTS: RECIST response rates were significantly lower compared with medical record reported with a concordance of 43.2% (95% CI: 28.0-58.4%). CONCLUSION: Subjective assessment of tumor response collected via traditional chart abstraction may overestimate benefit and limit the potential role of real-world evidence in value-based care research. The use of target lesion measurements presents an attractive alternative that better aligns with trial results.

Real-World Effectiveness of Dasatinib Versus Imatinib in Newly Diagnosed Patients With Chronic Myeloid Leukemia.

INTRODUCTION: Limited data exist comparing dasatinib with imatinib in clinical practice. This study assessed real-world outcomes associated with first-line (1L) dasatinib or imatinib treatment of chronic myeloid leukemia (CML). PATIENTS AND METHODS: This retrospective, observational, United States multisite cohort study analyzed electronic medical record data from adults with Philadelphia chromosome-positive (Ph+) CML in the chronic phase (CML-CP) after 1L dasatinib or imatinib between January 2014 and September 2018. Rates of and times to major molecular response (MMR) and deep molecular response (DMR) were assessed overall and in subgroups (low vs. intermediate/high risk, aged <65 vs. ≥65 years, low/normal vs. high body mass index [BMI]). RESULTS: The dasatinib cohort (n = 309) experienced higher rates of MMR (n = 304, 79% vs. 65%, P < .001) and DMR (44% vs. 25%, P < .001) vs. the imatinib cohort with shorter median times to MMR (11.9 vs. 14.7 months, P < .001) and DMR (30.3 vs. 66.1 months, P < .001). Patients with intermediate-/high-risk disease and those aged <65 years had higher MMR and DMR rates and achieved response earlier with dasatinib (P < .01). Patients with low-risk disease treated with dasatinib had higher rates of DMR (60% vs. 32%, P = .01). Across BMI strata, rates of MMR and DMR were higher with dasatinib (P < .05). CONCLUSIONS: Patients with CML-CP treated with 1L dasatinib achieved higher rates of, with shorter times to, MMR and DMR versus 1L imatinib. These clinically meaningful improvements were observed across subgroups.

Real-World Use of Fedratinib for Myelofibrosis Following Prior Ruxolitinib Failure: Patient Characteristics, Treatment Patterns, and Clinical Outcomes.

BACKGROUND: There is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice. PATIENTS AND METHODS: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. RESULTS: Twenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved ≥ 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01). CONCLUSION: Fedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib.

Better together? costs of first-line chemoimmunotherapy for advanced non-small cell lung cancer.

OBJECTIVES: Recent advances have created options for first-line (1L) treatment of advanced/metastatic non-small cell lung cancer (aNSCLC). The study objectives were to describe the utilization of 3 classes of 1L treatment-chemotherapy (CT), immunotherapy (IO), and chemoimmunotherapy (IO+CT)-and the total, third-party payer, direct health care costs. STUDY DESIGN: Retrospective, administrative claims database analysis of patients with aNSCLC who initiated 1L treatment between January 1, 2017, and May 31, 2019, with IO, CT, or IO+CT. METHODS: Microcosting enumerated health care resource utilization, including antineoplastic drug costs, using standardized costs. Generalized linear models estimated per-patient per-month (PPPM) costs during 1L treatment, and adjusted cost differences in 1L among treatment cohorts were calculated using recycled predictions. RESULTS: A total of 1317 IO-, 5315 CT-, and 1522 IO+CT-treated patients were identified. Utilization of CT declined from 72.3% to 47.6% between 2017 and 2019, replaced by use of IO+CT, which increased from 1.8% to 29.8%. Total PPPM costs in 1L were highest with IO+CT at $32,436, compared with $19,000 and $17,763 in the CT and IO cohorts, respectively. Adjusted analyses showed that PPPM costs were $13,933 (95% CI, $11,760-$16,105) higher in the IO+CT vs IO cohort (P < .001) and IO costs were $1024 (95% CI, $67-$1980) lower than CT (P = .04). CONCLUSIONS: IO+CT accounts for almost one-third of 1L aNSCLC treatment modalities, coinciding with a reduction in treatment with CT. Costs for patients treated with IO were lower than those for patients treated with both IO+CT and CT alone, driven primarily by antineoplastic drug and associated medical costs.