Patient characteristics associated with delayed time to adjuvant chemotherapy among women treated for stage I-IIIA breast cancer.

For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression.

Trends in chemotherapy use for early-stage breast cancer from 2006 to 2019.

BACKGROUND: Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). FINDINGS: Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1-14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8-30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration. CONCLUSIONS: While the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning.

FDA Approval Summary: Eflornithine for High-Risk Neuroblastoma Following Prior Multiagent, Multimodality Therapy.

On December 13, 2023, the U.S. Food and Drug Administration (FDA) approved eflornithine (IWILFIN, US WorldMeds) to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. The approval was based on an externally controlled trial (ECT) consisting of a single-arm trial, Study 3(b), compared to an external control derived from a National Cancer Institute (NCI)/Children's Oncology Group (COG)-sponsored clinical trial (Study ANBL0032) and supported by confirmatory evidence. In the protocol-specified primary analysis, the event-free survival (EFS) hazard ratio (HR) was 0.48 (95% confidence interval [CI]: 0.27, 0.85) and overall survival (OS) HR was 0.32 (95% CI: 0.15, 0.70). The most common adverse reactions (≥5%) were hearing loss, otitis media, pyrexia, pneumonia, and diarrhea. Notably, this is the first oncology drug approval which relies on an ECT as the primary clinical data to support substantial evidence of effectiveness. This was made possible by a distinctly high-quality, comparable external control dataset with consistent treatment effect estimations demonstrated in multiple sensitivity and supportive analyses. Eflornithine's manageable safety profile and strong nonclinical and mechanistic data provided further support for the approval, and the evidentiary package was evaluated in the context of high unmet need in a rare, life-threatening cancer.

Methodology for Using Real-World Data From Electronic Health Records to Assess Chemotherapy Administration in Women With Breast Cancer.

PURPOSE: Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. METHODS: In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015). RESULTS: In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status. CONCLUSION: We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.

Use of quantitative bias analysis to evaluate single-arm trials with real-world data external controls.

PURPOSE: Use of real-world data (RWD) for external controls added to single-arm trials (SAT) is increasingly prevalent in regulatory submissions. Due to inherent differences in the data-generating mechanisms, biases can arise. This paper aims to illustrate how to use quantitative bias analysis (QBA). METHODS: Advanced non-small cell lung cancer (NSCLC) serves as an example, where many small subsets of patients with molecular tumor subtypes exist. First, some sources of bias that may occur in oncology when comparing RWD to SAT are described. Second, using a hypothetical immunotherapy agent, a dataset is simulated based on expert input for survival analysis of advanced NSCLC. Finally, we illustrate the impact of three biases: missing confounder, misclassification of exposure, and outcome evaluation. RESULTS: For each simulated scenario, bias was induced by removing or adding data; hazard ratios (HRs) were estimated applying conventional analyses. Estimating the bias-adjusted treatment effect and uncertainty required carefully selecting the bias model and bias factors. Although the magnitude of each biased and bias-adjusted HR appeared moderate in all three hypothetical scenarios, the direction of bias was variable. CONCLUSION: These findings suggest that QBA can provide an intuitive framework for bias analysis, providing a key means of challenging assumptions about the evidence. However, the accuracy of bias analysis is itself dependent on correct specification of the bias model and bias factors. Ultimately, study design should reduce bias, but QBA allows us to evaluate the impact of unavoidable bias to assess the quality of the evidence.

Use of External Control Cohorts in Pediatric Brain Tumor Clinical Trials.

Why, when, and how to consider external control cohorts in pediatric brain tumor clinical trials.

Assessment of breast cancer chemotherapy dose reduction in an integrated healthcare delivery system.

PURPOSE: Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear. METHODS: In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy. RESULTS: Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years. CONCLUSION: Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women.

FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum.

On April 5, 2022, FDA granted accelerated approval to alpelisib for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. Efficacy was evaluated using real-world data (RWD) from EPIK-P1 (NCT04285723), a single-arm clinical study in patients 2 years of age and older with severe or life-threatening PROS who received alpelisib as part of an expanded access program (EAP) for compassionate use. The primary endpoint was confirmed radiologic response rate at week 24 as determined by blinded independent central review (BICR), using volumetric-based criteria given the atypical growth pattern and irregular shape of PROS lesions. Radiologic response was defined as a ≥20% reduction from baseline in the sum of measurable target lesion volume in up to three lesions. Of the 37 patients in the efficacy population, 27% [95% confidence interval (CI), 14-44] had a radiologic response at week 24. Duration of response (DOR) was an additional efficacy outcome measure, and among responders, 60% had a response lasting ≥12 months. Furthermore, supportive clinical documentation suggested early signals of clinical benefit (i.e., improvement in PROS-related signs and symptoms). The most common (≥10%) adverse reactions were diarrhea, stomatitis, and hyperglycemia.

Trends in new and persistent opioid use in older adults with and without cancer.

BACKGROUND: The impact of ongoing efforts to decrease opioid use on patients with cancer remains undefined. Our objective was to determine trends in new and additional opioid use in patients with and without cancer. METHODS: This retrospective cohort study used data from Surveillance, Epidemiology, and End Results program-Medicare for opioid-naive patients with solid tumor malignancies diagnosed from 2012 through 2017 and a random sample of patients without cancer. We identified 238 470 eligible patients with cancer and further focused on 4 clinical strata: patients without cancer, patients with metastatic cancer, patients with nonmetastatic cancer treated with surgery alone ("surgery alone"), and patients with nonmetastatic cancer treated with surgery plus chemotherapy or radiation therapy ("surgery+"). We identified new, early additional, and long-term additional opioid use and calculated the change in predicted probability of these outcomes from 2012 to 2017. RESULTS: New opioid use was higher in patients with cancer (46.4%) than in those without (6.9%) (P < .001). From 2012 to 2017, the predicted probability of new opioid use was more stable in the cancer strata (relative declines: 0.1% surgery alone; 2.4% surgery+; 8.8% metastatic cancer), than in the noncancer stratum (20.0%) (P < .001 for each cancer to noncancer comparison). Early additional use declined among surgery patients (‒14.9% and ‒17.5% for surgery alone and surgery+, respectively) but was stable among patients with metastatic disease (‒2.8%, P = .50). CONCLUSIONS: Opioid prescribing declined over time at a slower rate in patients with cancer than in patients without cancer. Our study suggests important but tempered effects of the changing opioid climate on patients with cancer.

FDA Approval Summary: Ribociclib Indicated for Male Patients with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer.

On December 10, 2021, the FDA expanded the indications for ribociclib to include male patients for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Ribociclib is now indicated in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy in adult patients, or with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy (ET), in postmenopausal women or in men. The efficacy of ribociclib + AI for male patients was primarily based on previous favorable benefit-risk assessments of ribociclib from MONALEESA-2 and MONALEESA-7 trials, and supported by COMPLEEMENT-1, an open-label, single-arm, multicenter clinical trial, in which 39 male patients (n = 3,246 total patients) received ribociclib + letrozole + goserelin/leuprolide. The overall response rate (ORR) based on confirmed responses in male patients with measurable disease at baseline was 46.9% [95% confidence interval (CI), 29.1-65.3], consistent with an ORR of 43.6% (95% CI, 41.5-45.8) in the overall population. Overall, adverse reactions occurring in male patients were similar to those occurring in female patients treated with ribociclib + ET. The efficacy of ribociclib + fulvestrant for male patients was primarily based on the previous findings of a favorable benefit-risk assessment from the MONALEESA-3 trial, supported by FDA review of clinical data of a limited number of male patients treated in clinical practice receiving ribociclib + fulvestrant. The known mechanism of action, biologic rationale, and clinical information available adequately demonstrate that the efficacy and safety of ribociclib + AI/fulvestrant are similar in male and female patients. This article summarizes the FDA's decision-making and data supporting the approval of ribociclib in male patients with breast cancer, and discusses regulatory insights.

A Descriptive Cohort Study of Drug Utilization Patterns Among Patients Hospitalized With Coronavirus Disease 2019 in the United States, January 2021-February 2022.

Background: There is a dearth of drug utilization studies for coronavirus disease 2019 (COVID-19) treatments in 2021 and beyond after the introduction of vaccines and updated guidelines; such studies are needed to contextualize ongoing COVID-19 treatment effectiveness studies during these time periods. This study describes utilization patterns for corticosteroids, interleukin-6 (IL-6) inhibitors, Janus kinase inhibitors, and remdesivir among hospitalized adults with COVID-19, over the entire hospitalization, and within hospitalization periods categorized by respiratory support requirements. Methods: This descriptive cohort study included United States adults hospitalized with COVID-19 admitted from 1 January 2021 through 1 February 2022; data included HealthVerity claims and hospital chargemaster. The number and distribution of patients were reported for the first 3 drug regimen lines initiated. Results: The cohort included 51 066 patients; the most common initial drug regimens were corticosteroids (23.4%), corticosteroids plus remdesivir (25.1%), and remdesivir (4.4%). IL-6 inhibitors and Janus kinase inhibitors were included in later drug regimens and were more commonly administered with both corticosteroids and remdesivir than with corticosteroids alone. IL-6 inhibitors were more commonly administered than Janus kinase inhibitors when patients received high-flow oxygen or ventilation. Conclusions: These findings provide important context for comparative studies of COVID-19 treatments with study periods extending into 2021 and later. While prescribing generally aligned with National Institutes of Health COVID-19 treatment guidelines during this period, these findings suggest that prescribing preference, potential confounding by indication, and confounding by prior/concomitant use of other therapeutics should be considered in the design and interpretation of comparative studies.

Association between antibiotics and adverse oncological outcomes in patients receiving targeted or immune-based therapy for hepatocellular carcinoma.

Background & Aims: Immune checkpoint inhibitors (ICIs) alone or in combination with other ICIs or vascular endothelial growth factor pathway inhibitors are therapeutic options in unresectable/metastatic hepatocellular carcinoma (HCC). Whether antibiotic (ATB) exposure affects outcome remains unclear. Methods: This study retrospectively analysed an FDA database including 4,098 patients receiving ICI (n = 842) either as monotherapy (n = 258) or in combination (n = 584), tyrosine kinase inhibitor (TKI) (n = 1,968), vascular endothelial growth factor pathway inhibitors (n = 480), or placebo (n = 808) as part of nine international clinical trials. Exposure to ATB within 30 days before or after treatment initiation was correlated with overall survival (OS) and progression-free survival (PFS) across therapeutic modality before and after inverse probability of treatment weighting (IPTW). Results: Of 4,098 patients with unresectable/metastatic HCC, of which 39% were of hepatitis B aetiology and 21% were of hepatitis C aetiology, 83% were males with a median age of 64 years (range 18-88), a European Collaborative Oncology Group performance status of 0 (60%), and Child-Pugh A class (98%). Overall, ATB exposure (n = 620, 15%) was associated with shorter median PFS (3.6 months in ATB-exposed vs. 4.2 months; hazard ratio [HR] 1.29; 95% CI 1.22, 1.36) and OS (8.7 months in ATB-exposed vs. 10.6 months; HR 1.36; 95% CI 1.29, 1.43). In IPTW analyses, ATB was associated with shorter PFS in patients treated with ICI (HR 1.52; 95% CI 1.34, 1.73), TKI (HR 1.29; 95% CI 1.19, 1.39), and placebo (HR 1.23; 95% CI 1.11, 1.37). Similar results were observed in IPTW analyses of OS in patients treated with ICI (HR 1.22; 95% CI 1.08, 1.38), TKI (HR 1.40; 95% CI 1.30, 1.52), and placebo (HR 1.40; 95% CI 1.25, 1.57). Conclusions: Unlike other malignancies where the detrimental effect of ATB may be more prominent in ICI recipients, ATB is associated with worse outcomes in this study across different therapies for HCC including placebo. Whether ATB is causally linked to worse outcomes through disruption of the gut-liver axis remains to be demonstrated in translational studies. Impact and Implications: A growing body of evidence suggests the host microbiome, frequently altered by antibiotic treatment, as an important outcome predictor in the context of immune checkpoint inhibitor therapy. In this study, we analysed the effects of early antibiotic exposure on outcomes in almost 4,100 patients with hepatocellular carcinoma treated within nine multicentre clinical trials. Interestingly, early exposure to antibiotic treatment was associated with worse outcomes not only in patients treated with immune checkpoint inhibitors but also in those treated with tyrosine kinase inhibitors and placebo. This is in contrast to data published in other malignancies, where the detrimental effect of antibiotic treatment may be more prominent in immune checkpoint inhibitor recipients, highlighting the uniqueness of hepatocellular carcinoma given the complex interplay between cirrhosis, cancer, risk of infection, and the pleiotropic effect of molecular therapies for this disease.

Evaluating Pneumonitis Incidence in Patients with Non-small Cell Lung Cancer Treated with Immunotherapy and/or Chemotherapy Using Real-world and Clinical Trial Data.

Pneumonitis is a potentially life-threatening complication of anticancer therapy, and future treatment decisions may be informed by characterizing patients receiving therapies in the real-world setting. In this study, the incidence of treatment-associated pneumonitis (TAP) was compared among patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors (ICI) or chemotherapies in either of two settings: randomized clinical trials (RCT) or real world data (RWD)-based clinical practice. Pneumonitis cases were identified using International Classification of Diseases codes (for RWD), or the Medical Dictionary for Regulatory Activities preferred terms (for RCTs). TAP was defined as pneumonitis diagnosed during treatment or within 30 days of the last treatment administration. Overall TAP rates in the RWD cohort were lower [ICI: 1.9%; 95% confidence interval (CI), 1.2-3.2; chemotherapy: 0.8%; 95% CI, 0.4-1.6] than overall rates in the RCT cohort (ICI: 5.6%; 95% CI, 5.0-6.2; chemotherapy: 1.2%; 95% CI, 0.9-1.5). Overall RWD TAP rates were similar to grade 3+ RCT TAP rates (ICI: 2.0%; 95% CI, 1.6-2.3; chemotherapy: 0.6%; 95% CI, 0.4-0.9). In both cohorts, higher TAP incidence was observed among patients with a past medical history of pneumonitis than those without, regardless of treatment group. On the basis of this sizable study leveraging RWD, TAP incidence was low in the RWD cohort, likely in part due to methodology used for RWD focusing on clinically significant cases. Past medical history of pneumonitis was associated with TAP in both cohorts. Significance: Pneumonitis is a potentially life-threatening complication of anticancer treatment. As treatment options expand, management decisions become increasingly complex, and there is a greater need to understand the safety profiles of the treatment options in the real-world setting. Real-world data serve as an additional source of valuable information to complement clinical trial data and inform understanding of toxicity in patients with non-small cell lung cancer receiving ICIs or chemotherapies.

The Association Between Baseline Hepatic or Renal Function and Clinical Outcomes for Patients With Non-Small Cell Lung Cancer Treated With a PD-1/PD-L1 Blocking Antibody Using Real-World and Trial Data.

Clinical trials have demonstrated the benefit of PD-1/PD-L1 blocking antibodies for the treatment of patients with advanced non-small cell lung cancer (NSCLC) in defined patient populations that often exclude patients with moderate or severe hepatic or renal impairment. We assessed the association between overall survival (OS) and baseline organ function in patients with advanced NSCLC treated with PD-1/PD-L1 blocking antibodies in real-world data (RWD; patient-level data from electronic health records) and pooled clinical trial data submitted to the US Food and Drug Administration (FDA). The Kaplan-Meier estimator was used to estimate OS in different subgroups based on organ function. Unadjusted and adjusted Cox proportional hazards models were used to estimate the association between OS and organ function. In this hypothesis-generating study, baseline renal impairment did not appear to be associated with OS, while patients with baseline liver impairment had shorter OS. RWD provided information on a broader range of renal and hepatic function than was evaluated in clinical trials and hold promise to complement trial data in better understanding populations not represented in clinical trials.

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Increasing Inclusiveness of Patient-Centric Clinical Evidence Generation in Oncology: Real-World Data and Clinical Trials.

Rapid advancements in cancer discovery, diagnosis, and treatment options available to patients with cancer have highlighted the need for enhancements in clinical trial design. The drug development process is costly, with more than 80% of trials failing to reach recruitment targets. Historical approaches to trial design are increasingly burdensome and lack real-world application in the intent-to-treat patient population. Equitable access to clinical trials combined with increased availability of real-world data are creating new opportunities for inclusiveness, improved outcomes, and evidence-based advances in therapies that will generate more generalizable data to better inform clinical decision-making. Clinical trials need to be inclusive if lifesaving data are not to be missed and investigational therapies are to be more accessible to a broader patient base. Real-world data can facilitate the conduct of studies that are identifying and understanding where disparities exist and developing new interventions to improve patient care. The clinical trial design process should be a multistakeholder and consensus- and evidence-driven process in which stakeholders are working together across the health care industry to close the care gap and ensure elimination of barriers that prevent equal access to specialized cancer care and advanced therapies available in clinical trials. The patient voice is essential throughout the trial process; however, it is often excluded from the design process. Integrating real-world data as well as ensuring patient involvement in early trial design during drug development can enhance enrollment and retention, leading to greater diversity.