scholarly journals Progress and challenges of integrated drug efficacy surveillance for uncomplicated malaria in Thailand

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Prayuth Sudathip ◽  
Aungkana Saejeng ◽  
Nardlada Khantikul ◽  
Thannikar Thongrad ◽  
Suravadee Kitchakarn ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
System Integration ◽  
Treatment Guidelines ◽  
Drug Efficacy ◽  
Fiscal Year ◽  
Efficacy Rate ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

Abstract Background Integrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017–2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure. Methods Routine patient data were extracted from the malaria information system for FY2018–FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan–Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin–piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax. Results The proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). Plasmodium falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine–artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy (chloroquine efficacy) was 98.5% in FY2018 (n = 2048), 99.1% in FY2019 (n = 2206), and 99.9% in FY2020 (n = 2448), and day 90 efficacy (primaquine efficacy) was 94.8%, 96.3%, and 97.1%, respectively. Conclusions In Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.

scholarly journals Progress and Challenges of Integrated Drug Efficacy Surveillance for Uncomplicated Malaria in Thailand

2021 ◽  
Author(s):  
Prayuth Sudathip ◽  
Aungkana Saejeng ◽  
Nardlada Khantikul ◽  
Thannikar Thongrad ◽  
Suravadee Kitchakarn ◽  
...  
Keyword(s):  
System Integration ◽  
Treatment Guidelines ◽  
Drug Efficacy ◽  
Fiscal Year ◽  
Efficacy Rate ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
History Of

Abstract BackgroundIntegrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017–2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure.MethodsRoutine patient data were extracted from the malaria information system for FY2018–FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan–Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin-piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax.ResultsThe proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). P. falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine-artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy was 98.5% in FY2018 (n = 2,048), 99.1% in FY2019 (n = 2,206), and 99.9% in FY2020 (n = 2,448), and day 90 efficacy was 94.8%, 96.3%, and 97.1%, respectively.ConclusionsIn Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.

191 Association of immune related adverse events with the efficacy of immune checkpoint inhibitors in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.

scholarly journals Choosing the Right Treatment Option for the Right R/M HNSCC Patient: Should We Adhere to PFE for First-Line Therapy?

2021 ◽  
Vol 11 ◽  
Author(s):  
Katharina Lübbers ◽  
Mykola Pavlychenko ◽  
Theresa Wald ◽  
Susanne Wiegand ◽  
Andreas Dietz ◽  
...  
Keyword(s):  
Cox Regression ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Real World Evidence ◽  
Consumption Benefit ◽  
Outcome Differences ◽  
The Right ◽  
High Level

BackgroundThe landmark EXTREME trial established cisplatin, 5-fluorouracil and cetuximab (PFE) as first-line chemotherapy (1L-ChT) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We were interested in outcome differences of R/M HNSCC in 1L-ChT and factors influencing outcome in certain subgroups, especially patients receiving PFE, and the value of PFE compared to other 1L-ChT regimens to provide real world evidence (RWE).MethodsFor this retrospective monocentric study, 124 R/M HNSCC patients without curative surgical or radiotherapy options receiving at least one cycle of 1L-ChT were eligible. We analyzed their outcome using Kaplan-Meier plot and Cox regression to identify predictors for prolonged survival.ResultsSubgroups benefiting significantly from PFE were patients suffering from an index HNSCC outside the oropharynx. The PFE regimen proved to be superior to all other 1L-ChT regimens in clinical routine. Significant outcome differences between PFE treatment within or outside controlled trials were not seen.ConclusionThis retrospective analysis provides RWE for factors linked to improved outcome. Subgroup analyses highlight the lasting value of PFE among the growing spectrum of 1L-ChT. Importantly, fit smokers with high level alcohol consumption benefit from PFE; considering the patient’s lifestyle factors, PFE should not be ignored in decision-making.

Outcomes of patients with metastatic colorectal carcinoma (MCRC) treated with first and second line chemotherapy at a multicenter cancer clinic

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13529-13529
Author(s):  
H. J. Lim ◽  
C. Lohrisch ◽  
C. Kollmannsberger ◽  
S. Gill ◽  
H. Kennecke ◽  
...  
Keyword(s):  
Median Number ◽  
Second Line ◽  
First Line ◽  
Related Factors ◽  
Second Line Chemotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Group B ◽  
Line Chemotherapy

13529 Background: In British Columbia (BC), FOLFIRI and FOLFOX were approved for the treatment of MCRC in 2002. The effect on survival of various treatment and patient related factors was determined for patients with MCRC treated with sequential doublet chemotherapy. Methods: Eligible patients received either FOLFOX or FOLFIRI first-line with a cross over to the alternative regimen for second-line therapy. Patient records were retrospectively reviewed for patient and disease characteristics, treatment, toxicity and survival. Analysis of survival was performed by the Kaplan-Meier method. Results: Between March 2002 and June 2004, 106 new patients met the criteria above. Sixty five patients were treated with a sequence of FOLFOX-FOLFIRI (Group A): 67% M, median age 57y, rectal 20%. Forty-one were treated with the sequence FOLFIRI-FOLFOX (Group B): 64% M, median age 58y, 27% rectal. Survival was statistically similar in both groups. Progression requiring second line chemotherapy within 4 weeks of a first line treatment was associated with inferior survival (13 months vs. 21 months (p<0.018). Grade 3 or 4 toxicity was experienced in 27.5% of the patients treated with FOLFOX and 22% of the patients treated with FOLFIRI. Conclusions: In the general population with MCRC, the median survival achieved with sequential doublet therapy is consistent with that reported in clinical trials. A superior sequence was not identified. The median number of first line chemotherapy cycles with FOLFOX and FOLFIRI was similar, reflecting the general clinical practice in BC to give 10 - 12 cycles of therapy followed by a planned break. Patients who required initiation of second line chemotherapy within 4 weeks of stopping the first line therapy experienced an inferior prognosis. Univariate and multivariate analysis showed no significance of sex, age, site (colon versus rectal), and ECOG status as predictive factors. [Table: see text] No significant financial relationships to disclose.

Treatment-free survival (TFS) after discontinuation of first-line nivolumab (NIVO) plus ipilimumab (IPI) or sunitinib (SUN) in intention-to-treat (ITT) and IMDC favorable-risk patients (pts) with advanced renal cell carcinoma (aRCC) from CheckMate 214.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 564-564 ◽  
Author(s):  
David F. McDermott ◽  
Brian I. Rini ◽  
Robert J. Motzer ◽  
Nizar M. Tannir ◽  
Bernard Escudier ◽  
...  
Keyword(s):  
Risk Groups ◽  
First Line ◽  
Free Survival ◽  
Intention To Treat ◽  
Poor Risk ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Clinical Trial Information

564 Background: TFS characterizes the antitumor activity of immuno-oncology agents after treatment discontinuation. In CheckMate 214, pts with IMDC intermediate/poor-risk aRCC who discontinued first-line NIVO+IPI experienced significantly longer TFS than those who discontinued SUN (McDermott et al, ESMO 2018). Here, we continue the analysis of TFS from CheckMate 214 in ITT and IMDC favorable-risk pts. Methods: Pts with previously untreated, predominantly clear cell aRCC were randomized 1:1 to intravenous NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 doses followed by NIVO 3 mg/kg every 2 weeks, or oral SUN 50 mg daily for 4 weeks on, 2 weeks off (6-week cycles). TFS was defined as the time from protocol therapy cessation to the start of subsequent systemic anticancer therapy or death, whichever occurred first. TFS in pts who discontinued NIVO+IPI or SUN was compared using Kaplan–Meier methods and log-rank tests. This analysis was conducted for all ITT (NIVO+IPI, 550; SUN, 546) and IMDC favorable-risk (NIVO+IPI, 125; SUN, 124) pts in CheckMate 214. Results: Among 463 NIVO+IPI and 477 SUN ITT pts who discontinued protocol therapy, the median TFS was 3.0 months with NIVO+IPI vs 1.3 months with SUN (HR [95% CI]; 0.54 [0.46–0.62]; P<0.0001); the TFS rates 2 years post-discontinuation were 21% vs 7%, respectively. In IMDC favorable-risk pts, 111 and 94 pts discontinued from NIVO+IPI and SUN, respectively. TFS in IMDC favorable-risk pts was also significantly longer with NIVO+IPI vs SUN (median, 6.3 vs 1.1 months; HR [95% CI]; 0.47 [0.34–0.65]; P<0.0001). The TFS rates 2 years post-discontinuation in favorable-risk pts were 29% for NIVO+IPI vs 13% for SUN. Conclusions: Similar to the TFS benefit seen in intermediate/poor-risk pts with aRCC, first-line therapy with NIVO+IPI resulted in reduced need for second-line therapy in ITT and IMDC favorable-risk pts compared with SUN. The durable TFS benefit across risk groups despite discontinuation of therapy provides further evidence of the encouraging benefit-risk profile of NIVO+IPI over SUN in pts with previously untreated aRCC. Clinical trial information: NCT02231749.

Survival outcomes with the use of immunotherapy (IO) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) at a large hybrid cancer institute.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21192-e21192
Author(s):  
Joanna Alyse Young ◽  
Christina Clarkson ◽  
Jiaxian He ◽  
Daniel Slaughter ◽  
Daniel Ernest Haggstrom ◽  
...  
Keyword(s):  
Real World ◽  
Smoking Status ◽  
Driver Mutations ◽  
First Line ◽  
Cox Models ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Treatment Type ◽  
Former Smokers

e21192 Background: Landmark trials have shown increased survival in pts who receive IO for NSCLC as compared to chemotherapy (chemo). Median overall survival (mOS) ranged from 17-26 months (mo); however, mOS in several published “real-world” retrospective studies are lower, ranging from 8-12 mo, with about 4-5 months on IO treatment. We sought to define mOS of pts with mNSCLC who received IO as monotherapy or in combination with chemo as first line therapy at Levine Cancer Institute. Methods: We retrospectively reviewed 315 adult pts with mNSCLC without driver mutations diagnosed between 2016 and 2019. The Kaplan-Meier method was used to estimate and compare OS between IO and IO + chemo. Univariate and multivariate Cox models were used to evaluate risk factors (RF) for OS. RFs considered included age, sex, race, smoking status, histology, first-line treatment type, and metastatic (mets) sites. Results: Baseline pt characteristics were: 40% female, 77% white, 20% Black, 34% current smokers and 60% former smokers. Median age was 69 years (45-88) in pts receiving IO alone and 63 years (28-84) in pts receiving IO + chemo. Tumor characteristics were: 76% adenocarcinoma and 17% squamous cell carcinoma. PD-L1 TPS distribution was: 39% for 0%, 22% for 1-49%, and 39% for ≥50%. Distribution of mets was 10% adrenal, 40% bone, 30% brain, 14% liver, 31% lung. mOS for pts receiving IO and IO + chemo as first line therapy was 17 and 14.8 mos, respectively (P = .209). Median duration of IO received was 4.25 months (0 to 43.6). mOS as stratified by PD-L1 TPS was 14.5 mos for PD-L1 0%, 13.3 mos for PD-L1 1-49%, and 19.5 mos for PD-L1 ≥50% (P = .163). OS was significantly different between IO and IO + chemo after adjusting for age. No OS differences were seen between white and Black or between all pts vs pts with brain mets (brain-specific interventions not reviewed). The table summarizes significant findings only (P < 0.05). Conclusions: Pts with mNSCLC treated first-line with IO either alone or with chemo at Levine Cancer Institute lived longer than those in similar published “real-world” cohorts. Median OS was highest in patients with PD-L1 TPS ≥50%, although not statistically significant. While not unusual to identify worse outcomes in those with bone and liver mets, interestingly brain metastasis was not associated with worse survival. In this cohort, when adjusted for age, IO alone trends toward improved survival. Although there was no OS difference based on race, further investigation will seek to uncover any other disparities contributing to outcomes, such as insurance status and zip code mapping. To our knowledge, this provides the largest analysis of this patient population outside of a clinical trial.[Table: see text]

scholarly journals Higher Serum Testosterone Levels Associated with Favorable Prognosis in Enzalutamide- and Abiraterone-Treated Castration-Resistant Prostate Cancer

2019 ◽  
Vol 8 (4) ◽  
pp. 489 ◽  
Author(s):  
Shinichi Sakamoto ◽  
Maihulan Maimaiti ◽  
Minhui Xu ◽  
Shuhei Kamada ◽  
Yasutaka Yamada ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Serum Testosterone ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Favorable Prognosis ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy ◽  
Kaplan Meier

Testosterone plays a significant role in maintaining the tumor microenvironment. The role of the target serum testosterone (TST) level in enzalutamide- (Enza) and abiraterone (Abi)-treated castration-resistant prostate cancer (CRPC) patients was studied. In total, 107 patients treated with Enza and/or Abi at Chiba University Hospital and affiliated hospitals were studied. The relationships between progression-free survival (PFS), overall survival (OS), and clinical factors were studied by Cox proportional hazard and Kaplan–Meier models. In the Abi and Enza groups overall, TST ≥ 13 ng/dL (median) (Hazard Ratio (HR) 0.43, p = 0.0032) remained an independent prognostic factor for PFS. In the Enza group, TST ≥ 13 ng/dL (median) was found to be a significant prognostic factor (HR 0.28, p = 0.0044), while, in the Abi group, TST ≥ 12 ng/dL (median) was not significant (HR 0.40, p = 0.0891). TST showed significant correlation with PFS periods (r = 0. 32, p = 0.0067), whereas, for OS, TST ≥ 13 ng/dL (median) showed no significant difference in the Abi and Enza groups overall. According to Kaplan–Meier analysis, a longer PFS at first-line therapy showed a favorable prognosis in the Enza group (p = 0.0429), while no difference was observed in the Abi group (p = 0.6051). The TST level and PFS of first-line therapy may be considered when determining the treatment strategy for CRPC patients.

scholarly journals Natural History Study of Idiopathic Multicentric Castleman Disease Identifies Effective Treatments for a Large Proportion of Patients but Treatment-Refractory Patients Remain

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1540-1540
Author(s):  
Sheila K Pierson ◽  
Yue Ren ◽  
Johnson Khor ◽  
Eric Haljasmaa ◽  
Jasira Ziglar ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Castleman Disease ◽  
Induced Response ◽  
First Line ◽  
International Consensus ◽  
Durable Response ◽  
Off Label ◽  
Multicentric Castleman Disease ◽  
First Line Therapy ◽  
Line Therapy

Background Human herpes-virus 8-negative/idiopathic multicentric Castleman disease (iMCD) is a rare inflammatory disorder involving multicentric lymphadenopathy with characteristic histopathology. Clinical presentation is heterogenous and includes cytokine-driven constitutional symptoms, cytopenias, systemic inflammation, and multi-organ dysfunction. International consensus treatment guidelines are based on a large cohort of case studies and a few clinical trials, but the available evidence is limited. Siltuximab, an anti-IL-6 therapy, is the only FDA-approved treatment for iMCD; 34% of patients achieved durable symptomatic and tumor response in the phase II trial. Tocilizumab, an anti-IL-6 receptor therapy, is frequently used off label and demonstrated promising results in an open-label study in Japan. The treatment guidelines recommend siltuximab ± corticosteroids (CS) as first-line therapy for all iMCD patients and tocilizumab as a substitute when siltuximab is not available. Rituximab, a CD20 antibody, is recommended as an alternate first-line therapy in patients who are non-severe and do not exhibit marked cytokine-driven symptoms. In all other patients, rituximab is recommended second-line; however, it has never been systematically evaluated in iMCD. Chemotherapies, immunosuppressants, and immunomodulators are recommended second- or third-line, but again, effectiveness is not well described. Better understanding of treatment effectiveness is urgently needed. Herein, we describe treatment and response in a real-world cohort of iMCD patients. Methods Data were collected and abstracted for 68 patients enrolled in an on-going IRB-approved natural history study of Castleman disease. Diagnosis is graded by an expert panel of clinicians and pathologists on an on-going basis; patients unlikely to have iMCD were excluded from analysis (N=12). Of the 56 patients included, 37 (66%) are expert panel-confirmed and 19 (34%) are awaiting confirmation. Durable response is defined as achieving ≥50% improvement in the proportion of abnormal iMCD minor clinical and laboratory diagnostic criteria sustained for ≥1 year. Small sample size prevented statistical comparisons. Results Median age at diagnosis is 33 years (range: 1-65 years). The cohort is 52.9% female, 63% white, and 4 (7%) patients died. Thirty-three unique drugs, including anti-IL-6 therapies, CS, chemotherapies, immunosuppressants, and others have been administered across the 56 patients. Rituximab is the most frequently used drug, administered to 39 (70%) patients. Siltuximab (29 patients, 52%) and tocilizumab (19 patients, 34%) are the next two most frequently used targeted therapies. There was a 52% response (15/29) to regimens inclusive of siltuximab, 50% response (9/18) to those inclusive of tocilizumab, and 25% response (9/26) to those inclusive of rituximab. Siltuximab±CS induced response in 15/24 (63%) patients, tocilizumab±CS in 4/7 (57%), and rituximab±CS in 2/13 (15%). Among the 37 expert-confirmed iMCD patients, we found a 58% response (11/19) to regimens inclusive of siltuximab, 47% (8/17) to those inclusive of tocilizumab, and 27% (7/26) to those inclusive of rituximab. Further, in these patients, siltuximab±CS induced response in 11/16 (69%), tocilizumab±CS in 3/6 (50%), and rituximab±CS in 1/6 (17%) patients. Of note, 3 of 4 deceased patients received both anti-IL-6 therapy and rituximab and all 4 received chemotherapies and immunosuppressants but did not respond to any drug. Discussion These data reveal that despite there being one FDA-approved treatment, iMCD is treated with a variety of agents. Among the full cohort, siltuximab±CS demonstrated a 63% durable response, which was higher than the response reported in the clinical trial (not statistically compared). This may reflect differences in response criteria and/or disease activity of patients in clinical trials versus real world settings. Siltuximab and tocilizumab have never been systematically compared; in this cohort they demonstrated similar response. Considering the morbidity and mortality of iMCD, these data suggest that current therapies demonstrate important activity. However, additional agents are needed for refractory patients, who have few options and are at risk of death due to disease progression. Further data are needed to compare groups and identify optimal treatment protocols. Disclosures Liu: BridgeBio Pharma: Employment, Equity Ownership. Gibson:EUSA Pharma: Employment. Kanhai:EUSA Pharma: Employment. Martin:EUSA Pharma: Employment. Srkalovic:Takeda: Speakers Bureau; Janssen: Speakers Bureau; Foundation Medicine: Speakers Bureau; EUSA Pharma: Speakers Bureau. Uldrick:Patent: Patents & Royalties: co-inventor on US Patent 10,001,483 entitled ; Celgene: Other: research support from Celgene through a CRADA at the NCI; Roche: Other: commercial research support through a CTA with Fred Hutchinson Cancer Research Center; Merck: Other: drug for a clinical trial from Merck through a CRADA with the NCI. van Rhee:Takeda: Consultancy; Sanofi Genzyme: Consultancy; Karyopharm Therapeutics: Consultancy; EUSA: Consultancy; Adicet Bio: Consultancy; Kite Pharma: Consultancy; Castleman Disease Collaborative Network: Consultancy. Fajgenbaum:Janssen Pharmaceuticals: Research Funding. OffLabel Disclosure: Tocilizumab, a monoclonal antibody directed against IL-6-receptor, is approved for use in rheumatoid arthritis in the US. It is frequently used off-label in idiopathic multicentric Castleman disease (iMCD) and is recommended as a substitute first-line therapy in the International Consensus iMCD treatment guidelines. Rituximab, a monoclonal antibody directed against CD20, is used in rheumatoid arthritis and other autoimmune and cancerous disorders. It is frequently used off-label in iMCD and is recommended as an alternate first-line or a second-line therapy in the International Consensus iMCD treatment guidelines. Corticosteroids are used broadly in iMCD and are recommended as needed as useful adjunctive therapy in the International Consensus iMCD treatment guidelines.

Efficacy of CDK4/6i in the visceral crisis setting: Result from a real-world database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1047-1047
Author(s):  
Shaheenah S. Dawood ◽  
Kaylen Brzozowski
Keyword(s):  
Real World ◽  
Metastatic Breast ◽  
Health Data ◽  
First Line ◽  
First Line Therapy ◽  
Resistant Disease ◽  
Hormone Receptor Positive ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Product Limit

1047 Background: The combination of the CDK4/6 inhibitors(CDK4/6i) and endocrine therapy has improved overall survival(OS) in patients(pts) with either endocrine sensitive or resistant disease who are not in visceral crisis. The goal of this retrospective analysis of a real world database was to look at the efficacy of CDK4/6i among pts with hormone receptor positive (HR+ve)/HER2-ve metastatic breast cancer(MBC) who present with visceral crisis at diagnosis. Methods: For this analysis, we utilized a federated network of de-identified health data representing approximately 64 million patient lives available through the TriNetX Platform. We identified 5966 pts who had HR+ve/HER2-ve MBC diagnosed between 2015 and 2020. OS was computed using the Kaplan Meier product limit method. Propensity score matching was performed on all comparisons of survival. Visceral crisis was defined as either liver metastases with liver dysfunction, lymphangitis with dyspnea or the presence of pancytopenia. Results: 906(15%) pts received CDK4/6i. OS any time after treatment among pts who did and did not receive CDK4/6i was significantly different (p=0.0002) favoring the group receiving CDK4/6i, with median OS at 59.6 months and 46.2 months and 2-year OS at 71.6% and 61.4% respectively. Among pts who received CDK4/6i versus another treatment as first line therapy, OS was significantly different(HR 0.7, 95%CI 0.57 – 0.86, p<0.0001), and median OS was 59.6 months and 41.5 months respectively. 336 pts with HR+ve mbc presented with visceral crisis at the time of diagnosis of whom 61(18%) received CDK4/6i therapy as first line therapy. Median OS among pts who did and did not have visceral crisis at diagnosis and received treatment was 8.1 months and 210 months respectively. OS any time after initial treatment was significantly different among pts with visceral crisis who did and did not receive CDK4/6i (p=0.01), with 2-year OS at 26.1% and 8.1% and median OS at 11 months and 6 months respectively Conclusions: The use of CDK4/6i in the presence of visceral crisis at diagnosis was associated with a 5 month improvement in OS compared to chemotherapy. Future clinical trials should explore the use of CDK4/6i in the setting of visceral crisis.

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