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 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.

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.

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.

Real-world observational study of current treatment patterns and outcomes in recurrent or locally advanced/metastatic non-small cell lung cancer.

BACKGROUND: Treatment for recurrent or advanced/metastatic non-small cell lung cancer (aNSCLC) has advanced in the past 5 years with immunotherapy (IO). This study sought to describe first-line (1L) aNSCLC treatment patterns and clinical outcomes. METHODS: In this retrospective, multisite cohort study, community oncologists reported data for randomly selected stage IIIB/IV, EGFR-/ALK wild-type aNSCLC patients who initiated 1L systemic therapy from 01/01/2016 to 12/31/2019. Follow-up was through November 2020. Demographics, clinical characteristics, treatment patterns, disease response, progression, and death/last follow-up date were described. Overall response rate (ORR) was calculated using tumor measurements applying RECIST v1.1 guidelines. Progression-free survival (PFS) and overall survival (OS) were calculated from 1L initiation by Kaplan-Meier method. RESULTS: 497 patients from 46 sites were included. The most common 1L regimens (%) were platinum-doublet chemotherapy plus IO (PDC+IO) (40.6%), PDC (29.4%), IO monotherapy (20.7%), and PDC+bevacizumab (6.2%). From 2016 to 2019, 1L PDC declined from 63% to 10%, whereas 1L PDC+IO increased from 14% to 58%. The ORRs were 64.9%, 32.9%, 60.2%, and 61.3% for 1L PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab, respectively. Median 1L PFS/OS (months) was 15.6/26.5, 5.3/13.7, 17.8/not reached, 10.8/18.6, respectively, for PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab. Among patients who received only 1L treatment (n = 299), 41.5% had no further therapy and were deceased. CONCLUSIONS: Although the 1L treatment paradigm has recently shifted to IO-based regimens, 41.5% did not survive past 1L. Median 1L PFS did not exceed 1.5 years and median OS remained limited across all 1L treatment groups, illustrating continued unmet aNSCLC therapeutic needs.

The Use and Knowledge of Validated Geriatric Assessment Instruments Among US Community Oncologists.

PURPOSE: The use of a standardized geriatric assessment (GA) to inform treatment decisions in older adults with cancer improves quality of life, reduces treatment-related toxicity, and is guideline-recommended. This study aimed to assess community oncologists' knowledge and utilization of GAs. METHODS: Between September 2019 and February 2020, practicing US-based oncologists were invited to attend live meetings and complete web-based surveys designed to collect information on treatment decision making and various practice-based challenges in oncology care. RESULTS: Among the 349 oncologists surveyed, 74% practiced in a community setting. Sixty percent did not use a formal GA to inform treatment decisions for any of their older patients; the most common reasons for not using a GA were "Too cumbersome to incorporate into routine practice" (44%) and "Adds no value beyond the comprehensive history and physical exam" (36%). Validated GA instruments used in routine clinical practice included: Mini-Mental State Exam (54%), Comprehensive Geriatric Assessment (23%), Cancer and Aging Research Group toxicity tool (12%), and Chemotherapy Risk Assessment Scale for High-Age Patients tool (9%). Nineteen percent of oncologists were not aware of any validated GA instruments. Eastern Cooperative Oncology Group performance status and comorbidities were the most frequently used assessment factors to inform treatment decisions (88% and 73%, respectively). CONCLUSION: Many oncologists have not incorporated GA tools because of perceptions that GAs are difficult to implement or do not add any value. Increasing education of the benefits of GA-directed therapy could help to increase GA utilization among community oncologists.

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.

Impact of social determinants of health on cancer care: a survey of community oncologists.

OBJECTIVE: Cancer survival rates have improved over the past few decades, yet socioeconomic disparities persist. Social determinants of health (SDOH) have consistently been shown to correlate with health outcomes. The objective of this study was to characterise oncologists' perceptions of the impact of SDOH on their patients, and their opinions on how these effects could be remediated. DESIGN: Cross-sectional survey of physicians. SETTING: Web-based survey completed prior to live meetings held between February and April 2020. PARTICIPANTS: Oncologists/haematologists from across the USA. EXPOSURE: Clinical practice in a community-based or hospital-based setting. MAIN OUTCOME AND MEASURE: Physician responses regarding how SDOH affected their patients, which factors represented the most significant barriers to optimal health outcomes and how the impact of SDOH could be mitigated through assistance programmes. RESULTS: Of the 165 physicians who completed the survey, 93% agreed that SDOH had a significant impact on their patients' health outcomes. Financial security/lack of insurance and access to transportation were identified most often as the greatest barriers for their patients (83% and 58%, respectively). Eighty-one per cent of physicians indicated that they and their staff had limited time to spend assisting patients with social needs, and 76% reported that assistance programmes were not readily accessible. Government organisations, hospitals, non-profit organisations and commercial payers were selected by 50% or more of oncologists surveyed as who should be responsible for delivering assistance programmes to patients with social needs; 42% indicated that pharmaceutical manufacturers should also be responsible. CONCLUSION: Our survey found that most oncologists were aware of the impact of SDOH on their patients but were constrained in their time to assist patients with social needs. The physicians in our study identified a need for more accessible assistance programmes and greater involvement from all stakeholders in addressing SDOH to improve health outcomes.

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma.

PURPOSE: Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination. PATIENTS AND METHODS: Data were retrospectively collected from patients with R/R DLBCL treated with lenalidomide monotherapy for comparison with tafasitamab + lenalidomide-treated patients (L-MIND). Key eligibility criteria were aligned with L-MIND. Estimated propensity score-based Nearest Neighbor 1:1 Matching methodology balanced the cohorts for nine prespecified prognostic baseline covariates. The primary endpoint was investigator-assessed best overall response rate (ORR). Secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and overall survival (OS). RESULTS: Data from 490 patients going through lenalidomide monotherapy were collected; 140 qualified for matching with the L-MIND cohort. The primary analysis included 76 patients from each cohort who received a lenalidomide starting dose of 25 mg/day. Cohort baseline covariates were comparable. A significantly better ORR of 67.1% (95% confidence interval, 55.4-77.5) was observed for the combination therapy versus 34.2% (23.7-46.0) for lenalidomide monotherapy [odds ratio, 3.89 (1.90-8.14); P < 0.0001]. Higher CR rates were achieved with combination therapy compared with lenalidomide monotherapy [39.5% (28.4-51.4) vs. 13.2% (6.5-22.9)]. Survival endpoints favored combination therapy. Lenalidomide monotherapy outcomes were similar to previously published data. CONCLUSIONS: RE-MIND enabled the estimation of the additional treatment effect achieved by combining tafasitamab with lenalidomide in patients with R/R DLBCL.

Expanded Access and Right To Try Requests: The Community Oncologist's Experience.

PURPOSE: For patients with cancer who have exhausted approved treatment options and for whom appropriate clinical trials are not available, access to investigational drugs through the US Food and Drug Administration's Expanded Access (EA) program has been an alternative since the program's inception more than 30 years ago. In 2018, federal Right To Try legislation was passed in the United States, creating a second pathway-one that bypasses the US Food and Drug Administration-to obtain unapproved drugs outside of clinical trials. The use of the two programs by community medical oncologists and hematologist-oncologists has not been studied. METHODS: Between October 2019 and February 2020, community oncologists-hematologists from across the United States completed web-based surveys about EA and Right To Try pathways for accessing unapproved drugs for their patients. Physicians were asked about their utilization of, and perceptions of, the two programs. RESULTS: Of the 238 physicians who completed the survey, 46% indicated that they had attempted to gain access to an investigational drug for a patient using the EA program, whereas 14% reported attempting to use Right To Try pathway to obtain an unapproved drug for a patient. Eighty-nine percent of those who tried to use the EA program reported success in obtaining the investigational drug versus 73% of those who attempted to use the Right To Try pathway. CONCLUSION: Our survey found that most community oncologists-hematologists were aware of both the EA and Right To Try pathways, but there is room for improvement in understanding and utilization of the programs.

Comparison of Solid Tumor Treatment Response Observed in Clinical Practice With Response Reported in Clinical Trials.

Importance: In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method's application in real-world evidence research. Objective: To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice. Design, Setting, and Participants: This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020. Exposures: Undergoing treatment with immunotherapy or targeted therapy. Main Outcomes and Measures: Tumor response was classified according to RECIST guidelines (ie, change in sum diameter of target lesions) post hoc with measurements derived from imaging scans and reports. Results: Among 1308 completed electronic case report forms, 956 forms (73.1%) had adequate data to classify real-world RECIST response. The greatest difference between physician-recorded responses and real-world RECIST-based responses was found in the proportion of complete responses: 118 responses (12.3%) vs 46 responses (4.8%) (P < .001). Among 609 patients in the metastatic melanoma population, complete responses were reported in 112 physician-recorded responses (18.4%) vs 44 real-world RECIST-based responses (7.2%) (P < .001), compared with 11 of 247 responses (4.5%) to 31 of 192 responses (16.1%) across pivotal trials of the same melanoma therapies. Conclusions and Relevance: These findings suggest that comparing tumor lesion sizes and categorizing treatment response according to RECIST guidelines may be feasible using real-world data. This study found that physician-recorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.

Effectiveness of Eribulin in Metastatic Breast Cancer: 10 Years of Real-World Clinical Experience in the United States.

INTRODUCTION: Eribulin was approved in the United States (US) in 2010 for patients with metastatic breast cancer (MBC) who previously received at least two chemotherapeutic regimens, including anthracycline and taxane in the adjuvant or metastatic setting. With significant changes to the treatment landscape over the past decade, assessment of the real-world effectiveness of eribulin in clinical practice when used according to the approved US indication is valuable. METHODS: Patients with MBC were identified by community oncologists through a retrospective, multi-site patient chart review; de-identified data were abstracted into electronic case report forms. Eligible patients initiated eribulin consistent with approved US indication between 1 January 2011 and 31 December 2017. Clinical outcomes assessed included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in all patients and those with triple negative breast cancer (TNBC). RESULTS: The analysis included 513 patients (median 59.0 years; 38.8% with Eastern Cooperative Oncology Group status ≥ 2). Eribulin was third-line therapy for 78.0% of patients, and fourth-line or later for the remainder. ORR was 54.4%, median PFS was 6.1 months (95% CI: 5.8, 6.6), and median OS was 10.6 months (95% CI 9.9, 11.7) in all patients. Among the 49.9% of patients with TNBC, ORR was 55.1%, median PFS was 5.8 months (95% CI 5.1, 6.4), and median OS was 9.8 months (95% CI 8.6, 11.0). CONCLUSION: The current retrospective chart review study reinforces the clinical effectiveness of eribulin in patients with MBC, including those with TNBC, when used according to the approved US indication in real-world clinical practice.

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years.

INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for relapsed or refractory large B-cell lymphoma (LBCL) with the Food and Drug Administration (FDA) approvals of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel). Although the incidence of LBCL is highest among patients age ≥ 65, clinical trials supporting approval of these 2 products primarily enrolled younger patients. Safety data for axi-cel and tis-cel in older patients is limited. METHODS: In this analysis, we queried the FDA Adverse Events Reporting System (FAERS) database for cases associated with axi-cel or tis-cel from the FDA approval dates for the LBCL indication for each product through December 31, 2019, and compared adverse events (AEs) reported for cases involving patients aged <65 and ≥ 65. RESULTS: A total of 804 cases were retrieved, with 333 (41%) involving patients age ≥ 65. Cytokine release syndrome (CRS) was the most common AE reported in both age groups. Cases involving older patients had a significantly higher proportion of neurological AEs, including CAR T-cell-related encephalopathy syndrome (8% vs. 4%, p = 0.03). Some individual clinical features of CRS were significantly more common among younger age group cases, including pyrexia (33% vs. 23%, p < 0.01), tachycardia (10% vs. 5%, p < 0.01), and thrombocytopenia (4% vs. 2%, p = 0.03). DISCUSSION: In this age-based analysis of FAERS reports for patients treated with axi-cel or tis-cel, we identified differences in patterns of AEs experienced. This large-scale post-marketing study complements clinical trial safety data and may help inform clinicians' decision making when treating adult patients with CAR-T cell therapy.

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.

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.

Neurological adverse events following CAR T-cell therapy: a real-world analysis.

Aim: To characterize real-world neurological adverse events (AEs) associated with chimeric antigen receptor T-cell therapies in patients with refractory/relapsed large B-cell lymphomas. Materials & methods: Postmarketing case reports from the US FDA AEs reporting system involving axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for large B-cell lymphomas were analyzed. Results: Of 804 AE cases identified (637 axi-cel, 167 tisa-cel), 428 (67%) of axi-cel cases and 43 (26%) of tisa-cel cases reported neurological AEs. Compared with cases without neurological AEs, significant associations were observed between neurological AEs and use of axi-cel, age ≥65 years, and the outcome of hospitalization. Conclusion: Neurological AEs were common with chimeric antigen receptor T-cell therapy in the real world and largely reflected those reported in clinical trials.

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).