scholarly journals Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis

2019 ◽  
Vol 46 (9) ◽  
pp. 1117-1126 ◽  
Author(s):  
Manuela Pardeo ◽  
Jianmei Wang ◽  
Nicolino Ruperto ◽  
Ekaterina Alexeeva ◽  
Vyacheslav Chasnyk ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Patient Characteristics ◽  
Phase Iii ◽  
Link Type ◽  
Serious Infection ◽  
Increased Risk ◽  
Serious Infections ◽  
Phase Iii Trials ◽  
Grade 3

Objective.To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ).Methods.Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112;ClinicalTrials.gov,NCT00642460) and pcJIA (n = 188;ClinicalTrials.gov,NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts.Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8–16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3–8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial.Conclusion.Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

WED 187 Infections in ocrelizumab recipients from phase III studies

2018 ◽  
Vol 89 (10) ◽  
pp. A26.3-A27
Author(s):  
Giovannoni Gavin ◽  
Hartung Hans-Peter ◽  
Comi Giancarlo ◽  
de Seze Jérôme ◽  
Hemmer Bernhard ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Phase Iii ◽  
System Organ Class ◽  
Primary Progressive Multiple Sclerosis ◽  
Upper Respiratory Tract ◽  
Infection Rates ◽  
Link Type ◽  
Serious Infection ◽  
Serious Infections ◽  
Tract Infections

BackgroundOcrelizumab Phase III study safety findings in relapsing (OPERA I/II [NCT01247324/NCT01412333]) and primary progressive multiple sclerosis (ORATORIO [NCT01194570]) were reported; infections and serious infections are reported here. Methods: Ocrelizumab patients received 600 mg intravenously every 24 weeks for 96 weeks (OPERA I/II) or ≥120 weeks (ORATORIO; 2 × 300 mg infusions 14 days apart every 24 weeks). Controls received interferon beta-1a 44 µg thrice weekly (IFNβ−1a; OPERA I/II) or placebo (ORATORIO). Infections were classified by MedDRA system organ class/preferred term.ResultsNon-serious infection rates in ocrelizumab-treated patients in OPERA were 58.4% (pooled analysis) and ORATORIO 69.8%; comparators were IFNβ−1a 52.4% and placebo 67.8%. Most infections were mild-to-moderate. Common infections (≥10% in either group) reported more in ocrelizumab treated patients were upper respiratory tract infections and either nasopharyngitis (OPERA) or influenza (ORATORIO);<1% of ocrelizumab-treated patients withdrew due to non-serious infections. Serious infections occurred in 1.3% (OPERA) and 6.2% (ORATORIO) of ocrelizumab-treated patients; comparators were IFNβ−1a 2.9% and placebo 5.9%. No infection-related deaths occurred in ocrelizumabtreated patients in OPERA; two deaths occurred in ORATORIO (aspiration pneumonia and pneumonia [unrelated per investigator, related per sponsor]). No opportunistic infections were reported.ConclusionSerious infection rates with ocrelizumab were numerically lower than with IFNβ−1a and similar compared with placebo.

066 Impact of long-term teriflunomide treatment on lymphocyte counts and infections in pooled temso and tower studies

2018 ◽  
Vol 89 (6) ◽  
pp. A27.1-A27
Author(s):  
Giancarlo Comi ◽  
Richard Macdonell ◽  
Myriam Benamor ◽  
Philippe Truffinet ◽  
Karthinathan Thangavelu ◽  
...  
Keyword(s):  
Treated Patient ◽  
Low Grade ◽  
Long Term Effects ◽  
Pooled Data ◽  
Link Type ◽  
Serious Infection ◽  
Serious Infections ◽  
Placebo Treated Patient ◽  
Grade 3

IntroductionIn TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide was associated with early reductions in mean lymphocyte counts, which remained within the normal range. Here, we analyse long-term effects of teriflunomide on lymphocyte counts and infections in pooled TEMSO/TOWER core and extension data (TEMSO extension, NCT00803049).MethodsPooled data from core studies are reported for patients receiving placebo or teriflunomide 14 mg. In the extensions, placebo-treated patients received active treatment; results from pooled core and extension studies are reported for the teriflunomide 14 mg group. Lymphocyte counts were obtained every 2 weeks until Week 24, and every 6 weeks thereafter. Lymphopenia was identified from 2 consecutive lymphocyte counts below LLN and graded by Common Terminology Criteria for Adverse Events.ResultsIn the core studies, placebo/teriflunomide-treated patients rarely experienced Grade 1 (0.7%/2.1%) or 2 (0.5%/1.4%) lymphopenia. Infections were reported in placebo-treated (40.0%/75.0%) and teriflunomide-treated (73.3%/20.0%) patients with Grade 1 or 2 lymphopenia, respectively. No patients with Grade 1 lymphopenia and 1 placebo-treated patient with Grade 2 lymphopenia developed a serious infection. In the combined core and extension studies, teriflunomide-treated patients (n=1354) experienced few Grade 1 (3.0%) or 2 (2.4%) lymphopenias; infections were reported in 25/40 (62.5%) and 19/33 (57.6%) patients, respectively, vs 718/1281 (56.0%) patients without lymphopenia. Serious infections occurred in patients without lymphopenia (47 patients [3.7%]) and in those with Grade 1 (1 [2.5%]) or Grade 2 (3 [9.1%]) lymphopenia. No Grade 3/4 lymphopenias were recorded. Despite the overall low rate of lymphopenia, occurrence and severity of lymphopenia will also be reported in subgroups of Asian and white patients.ConclusionIn long-term TEMSO and TOWER trials, low-grade lymphopenia was uncommon, with no reports of high-grade lymphopenia. Infection rates were similar in patients with or without lymphopenia, consistent with an immunomodulatory mechanism of action of teriflunomide with limited impact on protective immunity.

scholarly journals Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials

2018 ◽  
Vol 77 (12) ◽  
pp. 1710-1719 ◽  
Author(s):  
Nicolino Ruperto ◽  
Hermine I Brunner ◽  
Pierre Quartier ◽  
Tamàs Constantin ◽  
Nico M Wulffraat ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Phase Iii ◽  
Activity Score ◽  
Treatment Rate ◽  
Two Phase ◽  
Link Type

ObjectivesTo evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA).MethodsPatients (2–19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population.Results144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed.ConclusionResponse to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab.Trial registration numbersNCT00886769, NCT00889863, NCT00426218 and NCT00891046.

Longterm Safety and Effectiveness of the Anti-interleukin 6 Receptor Monoclonal Antibody Tocilizumab in Patients with Systemic Juvenile Idiopathic Arthritis in Japan

2014 ◽  
Vol 41 (4) ◽  
pp. 759-767 ◽  
Author(s):  
Shumpei Yokota ◽  
Tomoyuki Imagawa ◽  
Masaaki Mori ◽  
Takako Miyamae ◽  
Syuji Takei ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Response Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Good Tolerability ◽  
Link Type ◽  
American College Of Rheumatology ◽  
Interleukin 6 Receptor

Objective.To assess the longterm safety and effectiveness of tocilizumab (TCZ) in systemic-onset juvenile idiopathic arthritis (sJIA).Methods.The longterm extension phase of 2 pivotal studies (phase II with 11 patients and phase III with 56 patients) in patients with active sJIA was analyzed. Patients received open-label TCZ (8 mg/kg, every 2 weeks) without concomitant use of disease-modifying antirheumatic drugs.Results.In total, 67 patients were enrolled. All patients received corticosteroid at baseline. Median duration of exposure to TCZ was 3.4 years. Nine patients withdrew from the study [4 because of adverse events (AE), 4 because of the development of anti-TCZ antibodies, and 1 because of inadequate response]. Rates of AE and serious AE were 803.7/100 patient-years (PY) and 34.7/100 PY, respectively. The most common serious AE were infections (13.2/100 PY). No cases of malignancy or death were reported. Two serious infusion reactions were reported in patients testing negative for anti-TCZ antibodies. One definite macrophage activation syndrome (MAS) case and 1 potential MAS case were identified. American College of Rheumatology (ACR) response rates attained early in the TCZ treatment period were maintained throughout the study: at Week 168, JIA ACR 30, 50, 70, 90, and 100 response rates were 80.3%, 80.3%, 75.4%, 60.7%, and 18.0%, respectively. In total, 22 of 67 patients (32.8%) completely discontinued corticosteroids without flare.Conclusion.TCZ has demonstrated durability of effectiveness in the longterm treatment of children with sJIA and has shown good tolerability and a low discontinuation rate associated with AE, development of anti-TCZ antibodies, or inadequate response. (ClinicalTrials.govNCT00144599 and NCT00144612).(First Release March 15 2014; J Rheumatol 2014;41:759-67; doi:10.3899/jrheum.130690)

scholarly journals FRI0106 RISK FACTORS FOR SERIOUS INFECTIONS IN PATIENTS WITH RA INITIATING TREATMENT WITH BIOLOGIC DMARDS: A REAL-WORLD POPULATION-BASED OBSERVATIONAL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 632.1-633
Author(s):  
S. Suissa ◽  
P. Brassard ◽  
A. L. Dominique ◽  
T. Simon ◽  
M. Hudson
Keyword(s):  
Risk Factors ◽  
Risk Score ◽  
Real World ◽  
Treatment Initiation ◽  
Patient Characteristics ◽  
Baseline Risk ◽  
Biologic Dmards ◽  
Serious Infection ◽  
Increased Risk ◽  
Serious Infections

Background:Patients with RA are at increased risk of infection compared with the general population, but it is unclear whether this is due to the underlying disease or to immunosuppressive medications used to manage the disease.1Some biologic DMARDs (bDMARDs) have been associated with an increased risk of serious infection.2A large cohort study found no increased risk of serious infection in patients initiating abatacept compared with patients initiating other bDMARDs.3It is clinically important to identify which patients are at a higher risk of infections at the time of initiating treatment with a bDMARD. However, studies that assess risk factors for infection and derive corresponding risk scores of infection, especially at the time of bDMARD treatment initiation, are lacking or based on too few patients.4Objectives:To identify the risk factors for serious infections among patients with RA initiating treatment with a bDMARD in a real-world observational setting.Methods:The Truven MarketScan®Commercial and Supplemental Medicare databases were used to identify patients diagnosed with RA who initiated treatment with a bDMARD between January 2007 and December 2015. Patients were followed from treatment initiation until the occurrence of a serious infection requiring hospitalisation, the end of enrolment or 31 December 2015, whichever came first. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serious infection associated with baseline risk factors including demographics, the presence of co-morbidities, prior hospitalised infections and medications. An infection risk score was developed using the independent risk factors found to be significant in the model.Results:The study cohort included 84,308 patients initiating treatment with a bDMARD, mainly etanercept (36.7%), adalimumab (29.3%), infliximab (12.4%), rituximab (7.3%) and abatacept (6.8%). During a mean follow-up of 6.6 months, 1724 patients were hospitalised for a serious infection (incidence rate 3.7/100 persons per year). The baseline risk factors significantly and independently associated with serious infections were age, prior hospitalisation for infection, hypertension, diabetes, lymphoma, asthma, chronic obstructive pulmonary disease, cardiovascular disease, other autoimmune disease, corticosteroid use and antibiotic use. The infection risk score, with a possible range of 0 to 15, had a mean (SD) value of 2.6 (1.9) with range 0–12.5. The HR (95% CI) of serious infection was 1.43 (1.40–1.45) for every unit increase in the risk score. Relative to patients with a score of 0, the HR (95% CI) of serious infection for a risk score of 5 was 5.9 (5.3–6.5), and for a risk score of 10 was 34.5 (28.5–41.6).Conclusion:In this large, real-world cohort of patients with RA who were initiating treatment with a bDMARD, several patient characteristics were found to independently predict the subsequent risk of serious infection. The risk score, based on easily available patient characteristics, can be a simple and useful tool for the clinician to identify patients at higher risk of infection at the time of bDMARD initiation for the treatment of RA.References:[1]Doran MF, et al.Arthritis Rheum2002;46:2287–93.[2]Singh JA.Curr Rheumatol Rep2016;18:61.[3]Montastruc F, et al.Semin Arthritis Rheum2019;48:1053–8.[4]Jani M, et al.Curr Opin Rheumatol2019;31:285–92.Acknowledgments:Joanna Wright (editorial assistance, Caudex; funding: Bristol-Myers Squibb).Disclosure of Interests:Samy Suissa Grant/research support from: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Consultant of: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis (advisory board meetings), Speakers bureau: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Paul Brassard: None declared, Alyssa L. Dominique Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Teresa Simon Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Marie Hudson: None declared

scholarly journals 1095. Investigation of Risk Factors Associated with Serious Bacterial, Viral and Invasive Fungal Infections in Hematologic Patients on Ibrutinib

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S576-S577
Author(s):  
Thomas Holowka ◽  
Harry Cheung ◽  
Maricar F Malinis ◽  
Sarah Perreault ◽  
Iris Isufi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Fungal Infections ◽  
Antimicrobial Prophylaxis ◽  
Hematologic Malignancy ◽  
Invasive Fungal Infections ◽  
Risk Of Infection ◽  
Factors Associated ◽  
Serious Infection ◽  
Increased Risk ◽  
Serious Infections

Abstract Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p &lt; 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p &lt; 0.001), neutropenia (OR 3.6, p &lt; 0.01), lymphopenia (OR 2.4, p &lt; 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p &lt; 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures

scholarly journals COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3573
Author(s):  
Alfred Chung Pui So ◽  
Harriet McGrath ◽  
Jonathan Ting ◽  
Krishnie Srikandarajah ◽  
Styliani Germanou ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Safety Data ◽  
Vaccine Safety ◽  
Phase Iii ◽  
Solid Malignancy ◽  
Common Grade ◽  
Phase Iii Trials ◽  
Oncology Care ◽  
Grade 3 ◽  
Oncology Centre

Emergency approval of vaccines against COVID-19 provides an opportunity for us to return to pre-pandemic oncology care. However, safety data in cancer patients is lacking due to their exclusion from most phase III trials. We included all patients aged less than 65 years who received a COVID-19 vaccine from 8 December 2020 to 28 February 2021 at our London tertiary oncology centre. Solicited and unsolicited vaccine-related adverse events (VRAEs) were collected using telephone or face-to-face consultation. Within the study period, 373 patients received their first dose of vaccine: Pfizer/BioNTech (75.1%), Oxford/AstraZeneca (23.6%), Moderna (0.3%), and unknown (1.1%). Median follow-up was 25 days (5–85). Median age was 56 years (19–65). Of the patients, 94.9% had a solid malignancy and 76.7% were stage 3–4. The most common cancers were breast (34.0%), lung (13.4%), colorectal (10.2%), and gynaecological (10.2%). Of the patients, 88.5% were receiving anti-cancer treatment (36.2% parenteral chemotherapy and 15.3% immunotherapy), 76.1% developed any grade VRAE of which 2.1% were grade 3. No grade 4/5 or anaphylaxis were observed. The most common VRAEs within 7 days post-vaccination were sore arm (61.7%), fatigue (18.2%), and headaches (12.1%). Most common grade 3 VRAE was fatigue (1.1%). Our results demonstrate that COVID-19 vaccines in oncology patients have mild reactogenicity.

National Cancer Institute–United States strategy regarding intraperitoneal chemotherapy for ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 26-28 ◽  
Author(s):  
E. L. Trimble ◽  
M. C. Christian
Keyword(s):  
Ovarian Cancer ◽  
National Cancer Institute ◽  
Phase Iii ◽  
Cooperative Groups ◽  
Advocacy Organizations ◽  
Increased Risk ◽  
Phase Iii Trials ◽  
Educational Campaign ◽  
Clinically Significant ◽  
Further Development

On the basis of three large randomized phase III trials, the National Cancer Institute (NCI) issued a Clinical Announcement in January 2006 recommending that women with optimally debulked stage III ovarian cancer and their physicians consider a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy. The combination of IV and IP chemotherapy is associated with a clinically significant benefit in survival, although it does also confer an increased risk of toxicity compared to IV chemotherapy alone. The NCI Clinical Announcement was issued as part of a broader educational campaign, designed in conjunction with professional societies, cancer centers, Clinical Trials Cooperative Groups, and cancer advocacy organizations. The further development of IP chemotherapy in ovarian cancer requires additional clinical and translational research

scholarly journals Inferences About Drug Safety in Phase III Trials in Oncology: Examples From Advanced Prostate Cancer

2020 ◽  
Author(s):  
Joshua Z Drago ◽  
Mithat Gönen ◽  
Gita Thanarajasingam ◽  
Chana A Sacks ◽  
Michael J Morris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Safety ◽  
Advanced Prostate Cancer ◽  
Patient Characteristics ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Statistical Uncertainty ◽  
Cancer Disease ◽  
Disease States ◽  
Phase Iii Trials

Abstract Background Safety is a central consideration when choosing between multiple medications with similar efficacy. We aimed to evaluate whether adverse event (AE) profiles of 3 such drugs in advanced prostate cancer could be distinguished based on published literature. Methods We assessed consistency in AE reporting, AE risk in placebo arms, and methodology used for risk estimates and quantification of statistical uncertainty in randomized placebo-controlled phase III trials of apalutamide, enzalutamide, and darolutamide in advanced prostate cancer. Results Seven included clinical trials enrolled a total of 9215 participants (range = 1051-1715 per trial) across 3 prostate cancer disease states. Within disease states, baseline patient characteristics appeared similar between trials. Of 54 distinct AE types in total, only 3 (fatigue, hypertension, and seizure) were reported by all 7 trials. Absolute risks of AEs in the placebo arms differed systematically and more than twofold between trials, which was associated with visit frequency and resulted in different degrees of uncertainty in AE profiles between trials. No trial used inferential methodology to quantify statistical uncertainty in AE risks, but 6 of 7 trials drew overall conclusions. Two trials concluded that there was no elevated AE risk because of the intervention, including the trial of darolutamide, which had the greatest statistical uncertainty. Conclusions Rigorous comparison of drug safety was precluded by heterogeneity in AE reporting, variation in AE risks in the placebo arms, and lack of inferential statistical methodology, underscoring considerable opportunities to improve how AE data are collected, analyzed, and interpreted in oncology trials.

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