scholarly journals POS0619 MODELLING OF DISEASE ACTIVITY IN PATIENTS WITH INFLAMMATORY ARTHROPATHIES TREATED WITH ETANERCEPT ORIGINATOR OR BIOSIMILAR AS FIRST-LINE BIOLOGIC IN AN AUSTRALIAN REAL-WORLD DATASET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Data ◽  
Real World ◽  
Rank Test ◽  
P Value ◽  
Continuous Variables ◽  
Linear Quadratic ◽  
First Line ◽  
Modest Improvement ◽  
Over Time

Background:The availability of biosimilars as non-proprietary versions of established biologic disease-modifying anti-rheumatic drugs (bDMARDs) is enabling greater access for patients with rheumatic diseases to effective medications at a lower cost. Since April 2017 both the originator and a biosimilar for etanercept (trade names Enbrel and Brenzys, respectively) have been available for use in Australia.Objectives:[1]To model effectiveness of etanercept originator or biosimilar in reducing Disease Activity Score 28-joint count C reactive protein (DAS28CRP) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with either drug as first-line bDMARD[2]To describe persistence on etanercept originator or biosimilar as first-line bDMARD in patients with RA, PsA or ASMethods:Clinical data were obtained from the Optimising Patient outcomes in Australian rheumatoLogy (OPAL) dataset, derived from electronic medical records. Eligible patients with RA, PsA or AS who initiated etanercept originator (n=856) or biosimilar (n=477) as first-line bDMARD between 1 April 2017 and 31 December 2020 were identified. Propensity score matching was performed to select patients on originator (n=230) or biosimilar (n=136) with similar characteristics in terms of diagnosis, disease duration, joint count, age, sex and concomitant medications. Data on clinical outcomes were recorded at 3 months after baseline, and then at 6-monthly intervals. Outcomes data that were missing at a recorded visit were imputed.Effectiveness of the originator, relative to the biosimilar, for reducing DAS28CRP over time was modelled in the matched population using linear mixed models with both random intercepts and slopes to allow for individual heterogeneity, and weighting of individuals by inverse probability of treatment weights to ensure comparability between treatment groups. Time was modelled as a combination of linear, quadratic and cubic continuous variables.Persistence on the originator or biosimilar was analysed using survival analysis (log-rank test).Results:Reduction in DAS28CRP was associated with both time and etanercept originator treatment (Table 1). The conditional R-squared for the model was 0.31. The average predicted DAS28CRP at baseline, 3 months, 6 months, 9 months and 12 months were 4.0 and 4.4, 3.1 and 3.4, 2.6 and 2.8, 2.3 and 2.6, and 2.2 and 2.4 for the originator and biosimilar, respectively, indicating a clinically meaningful effect of time for patients on either drug and an additional modest improvement for patients on the originator.Median time to 50% of patients stopping treatment was 25.5 months for the originator and 24.1 months for the biosimilar (p=0.53). An adverse event was the reason for discontinuing treatment in 33 patients (14.5%) on the originator and 18 patients (12.9%) on the biosimilar.Conclusion:Analysis using a large national real-world dataset showed treatment with either the etanercept originator or the biosimilar was associated with a reduction in DAS28CRP over time, with the originator being associated with a further modest reduction in DAS28CRP that was not clinically significant. Persistence on treatment was not different between the two drugs.Table 1.Respondent characteristics.Fixed EffectEstimate95% Confidence Intervalp-valueTime (linear)0.900.89, 0.911.5e-63Time (quadratic)1.011.00, 1.011.3e-33Time (cubic)1.001.00, 1.007.1e-23Originator0.910.86, 0.960.0013Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platform.Supported in part by a research grant from Investigator-Initiated Studies Program of Merck & Co Inc, Kenilworth, NJ, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co Inc, Kenilworth, NJ, USA.Disclosure of Interests:Claire Deakin: None declared, Geoff Littlejohn Consultant of: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus., Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Tegan Smith: None declared, Catherine OSullivan: None declared, Paul Bird Speakers bureau: Eli Lilly, abbvie, pfizer, BMS, UCB, Gilead, Novartis

scholarly journals Utility of routinely collected electronic health records data to support effectiveness evaluations in inflammatory bowel disease: a pilot study of tofacitinib

2021 ◽  
Vol 28 (1) ◽  
pp. e100337
Author(s):  
Vivek Ashok Rudrapatna ◽  
Benjamin Scott Glicksberg ◽  
Atul Janardhan Butte
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pilot Study ◽  
Disease Activity ◽  
Real World ◽  
Bowel Disease ◽  
P Value ◽  
Health Records ◽  
Real World Evidence ◽  
Inflammatory Bowel

ObjectivesElectronic health records (EHR) are receiving growing attention from regulators, biopharmaceuticals and payors as a potential source of real-world evidence. However, their suitability for the study of diseases with complex activity measures is unclear. We sought to evaluate the use of EHR data for estimating treatment effectiveness in inflammatory bowel disease (IBD), using tofacitinib as a use case.MethodsRecords from the University of California, San Francisco (6/2012 to 4/2019) were queried to identify tofacitinib-treated IBD patients. Disease activity variables at baseline and follow-up were manually abstracted according to a preregistered protocol. The proportion of patients meeting the endpoints of recent randomised trials in ulcerative colitis (UC) and Crohn’s disease (CD) was assessed.Results86 patients initiated tofacitinib. Baseline characteristics of the real-world and trial cohorts were similar, except for universal failure of tumour necrosis factor inhibitors in the former. 54% (UC) and 62% (CD) of patients had complete capture of disease activity at baseline (month −6 to 0), while only 32% (UC) and 69% (CD) of patients had complete follow-up data (month 2 to 8). Using data imputation, we estimated the proportion achieving the trial primary endpoints as being similar to the published estimates for both UC (16%, p value=0.5) and CD (38%, p-value=0.8).Discussion/ConclusionThis pilot study reproduced trial-based estimates of tofacitinib efficacy despite its use in a different cohort but revealed substantial missingness in routinely collected data. Future work is needed to strengthen EHR data and enable real-world evidence in complex diseases like IBD.

scholarly journals POS0942 THE NEGATIVE IMPACT OF UNDIAGNOSED DEPRESSION IN AXIAL SPONDYLOARTHROPARTHY: RESULTS OF A SCREENING STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 734.1-734
Author(s):  
S. Maguire ◽  
F. B. O’shea
Keyword(s):  
Disease Activity ◽  
Negative Impact ◽  
Depression Scale ◽  
Clinic Visit ◽  
Categorical Variables ◽  
P Value ◽  
Continuous Variables ◽  
Numerical Result ◽  
Co Morbidity ◽  
Patient Reported

Background:Previous research in axial spondyloarthropathy(axSpA) has shown this population to have a high prevalence of depression. This co-morbidity has been previously shown to impact disease activity in patients with rheumatic disease.Objectives:The purpose of this study was to screen for early signs of depression using two validated tools, the Patient Health Questionaire-9 (PHQ-9) and the Hospital Anxiety and Depression Scale for depression (HADs-D) in patients with known axSpA.Methods:AxSpA patients attending the Rheumatology department in St James’ Hospital between February and October 2020 were invited to take a self-administered survey which included the PHQ-9 and the HADs-D. Scores from the HADs-D yielded a numerical result which was then categorised as normal, borderline or abnormal. PHQ-9 numerical results were categorised as normal, mild, moderate, moderate/severe or severe. Patients with a known diagnosis of depression were excluded. In addition to baseline demographics, patient reported outcomes from the clinic visit were also recorded.Data analysis was performed using IBM SPSS version 26. Continuous variables were recorded as means, categorical variables as frequencies with percentages. A one-way analysis of variance analysis (ANOVA) was used to determine significance of variation in outcomes between patient outcomes as determined by the HADs-D and PHQ-9. A p-value of <0.05 was deemed significant. Consent was obtained prior to participation. Approval was received from the St James’/Tallaght Hospital Joint Ethics Committee.Results:In total 71 axSpA patients took part in the survey. The population was 70.4%(50) males and 29.5%(21) female, with an average age 47.9 years and mean disease duration 19.7 years (mean outcomes: BASDAI 4.08, BASFI 3.62, BASMI 3.54, ASQoL 6.79). Overall, 7 (9.9%) participants recorded abnormal HADs-D scores, while 17 (23.9%) recorded moderate to severe PHQ-9 scores indicative of underlying depression. AxSpA females had higher mean HADs-D scores (7.5 vs 4.8, p=0.01) than males, with abnormal scores in 19%(4) of females and 6% (3) of males. No significant differences were found in PHQ-9 scores between genders.Analysis revealed significantly worse BASDAI (6.27 vs 3.42, p<0.01) and AQoL scores (12.57 vs 5.26, p<0.01) in axSpA patients with abnormal compared to normal HADs-D scores. No significant differences were noted in BASFI, BASMI or baseline demographics. A similar pattern was noted on analysis of PHQ-9 scores, with significantly worse BASDAI (7.9 vs 2.55, p<0.01), BASFI (8.05 vs 2.33, p<0.01) and ASQoL (19.5 vs 2.62, p<0.01) noted in those scoring as severe compared to normal. No significant differences were detected in BASMI scores or baseline demographics.Conclusion:A high percentage of axSpA patients recorded high HADs-D and PHQ-9 scores concerning for undiagnosed depression. These patients were noted to have significantly worse disease activity and quality of life as compared to patients with normal scores. Clinicians treating axSpA should consider screening for depression in this population.Disclosure of Interests:Sinead Maguire Speakers bureau: Speaker fee from Jassen, Grant/research support from: Recipient of the Gilead Inflammation Fellowship Grant, Finbar Barry O’Shea: None declared

scholarly journals AB0337 TOFACITINIB MONOTHERAPY OR COMBINED WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS SHOW SIMILAR RETENTION OVER FOUR YEARS. REPORT FROM RHUMADATA ®

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1467.1-1467
Author(s):  
D. Choquette ◽  
L. Bessette ◽  
L. Choquette Sauvageau ◽  
I. Ferdinand ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Treatment Initiation ◽  
Retention Rate ◽  
Janus Kinase ◽  
P Value ◽  
Research Support ◽  
Medication Discontinuation ◽  
Kaplan Meier

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

Sequence decision making for cabazitaxel (Cbz) versus abiraterone (Abt) or enzalutamide (Enz) post-docetaxel (Dtx) in a publicly funded health care system.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 57-57
Author(s):  
Alexander Watson ◽  
Richard Gagnon ◽  
Eugene Batuyong ◽  
Nimira S. Alimohamed ◽  
Richard M. Lee-Ying
Keyword(s):  
Real World ◽  
Performance Status ◽  
Patient Choice ◽  
Rank Test ◽  
First Line ◽  
Chi Square ◽  
The Real ◽  
Therapeutic Decisions ◽  
Chi Square Test ◽  
Castrate Resistant

57 Background: The TROPIC trial demonstrated an overall survival (OS) benefit of Cbz after Dtx in metastatic castrate-resistant prostate cancer (mCRPC). However, the novel anti-androgens (NAA) Abi and Enz have demonstrated similar improvements post-Dtx. The recent CARD trial suggests Cbz may provide the greatest OS benefit in selected patients who were rapid progressors ( < 12 months, RP) on first NAA, however Cbz use and efficacy in the real-world is uncertain. We sought to quantify the real-world use of Cbz and evaluate outcomes post-Dtx. Methods: mCRPC patients who received Dtx at the two tertiary referral centres in the Canadian province of Alberta from October 2012 (Cbz funding approval) to December 31st 2017 were assessed. We examined Cbz eligibility per TROPIC and CARD trial criteria, tracked therapies received, and documented objective and subjective reasoning for therapeutic decisions. OS was measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes. The Chi-Square test was used to compare relative therapy utilization. Results: 463 mCRPC patients received Dtx over the study period, including 83 (18%) for castrate sensitive disease. At Dtx progression, 262 patients (56%) were eligible for Cbz per TROPIC trial criteria, while only 162 (62%) of those were RP on first NAA. Post-Dtx OS was lower among TROPIC-eligible patients receiving Cbz compared to those receiving Abi or Enz (9.1 vs 14.2 months, p = 0.001). This OS difference was not demonstrated among RP patients (11.2 vs 12 months, p = 0.664). The most common reasons for TROPIC ineligibility were Dtx intolerance (13%), serious comorbidities (12%), unacceptable blood counts (11%), performance status (9%) or, for CARD ineligible patients, no progression within 12 months on first NAA (38%). The most common agent immediately post-Dtx was Abi (n = 180, 39%), followed by Enz (n = 129, 28%). Significantly fewer patients (n = 56, 12%) received Cbz immediately post-Dtx (p = 0.001), and 149 (32%) received Cbz overall. First line post-Dtx, 286 patients (62%) did not have a documented discussion about Cbz, and in 172 cases (38%) consideration of Cbz was never documented. Patient choice against Cbz chemotherapy was recorded in 15% of discussions. Conclusions: In a real-world cohort of mCRPC patients, Cbz was a significantly less common choice than Abi or Enz after progression on Dtx. In a majority of these cases, no first line discussion of Cbz was documented, and in documented discussions, patient choice was the driving factor in a minority. OS post-Dtx in patients who met TROPIC trial criteria was lower for those receiving Cbz, noting that, unlike in TROPIC, these patients also received NAAs. This OS difference was not seen in those who also progressed rapidly on first NAA. These data suggest ongoing hesitation towards Cbz use in mCRPC and support careful selection of patients who may obtain benefit.

Rituximab (Mabthera) Improves the Treatment Results of DHAP-VIM-DHAP and ASCT in Relapsed/Progressive Aggressive CD20+ NHL. A Prospective Randomized HOVON Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 328-328 ◽  
Author(s):  
Edo Vellenga ◽  
Annelise Notenboom ◽  
Mars van ‘t Veer ◽  
Josée Zijlstra ◽  
Willem E. Fibbe ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Response Duration ◽  
Rank Test ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Post Transplantation ◽  
Free Survival ◽  
Significant Difference ◽  
First Line Treatment

Abstract A total of 239 patients with relapsed/progressive aggressive CD20+ NHL after/during adriamycin containing regimens, were recruited to the randomized HOVON-44 trial comparing DHAP-VIM-DHAP followed by BEAM and autologous stem cell re-infusion (ASCT)(“DHAP-arm”) with DHAP-VIM-DHAP in conjunction with Rituximab (375 mg/m2) and ASCT (“R-DHAP arm”). Of the included patients, 202 were evaluable and randomized to the DHAP arm (n=101) or R-DHAP arm (n=101). Only patients with CR/PR after two courses of intensive chemotherapy were eligible for ASCT. Patients were well balanced for risk factors. In both arms the majority of patients had not been exposed to Rituximab during first line treatment. As of July 2006, median follow-up of all patients still alive is 24.5 months. After two courses of chemotherapy PR/CR was obtained in 49 % of the patients in the DHAP arm and 77% in the R-DHAP arm (p=<.01;intention to treat analysis). Post-transplantation PR/CR was obtained in 41% and 58% of the patients respectively (p=.40). A significant difference between both arms was observed for failure free survival (FFS), disease free survival (DFS) and overall survival (OS) in favor of the Rituximab arm (p<.05, table 1). The less pronounced difference in OS between both arms is most likely due to the fact that non-responding or relapsing patients in the DHAP arm received salvage treatment with a Rituximab containing regimen. Additionally, a subgroup analysis was performed according to type of response to first-line treatment:1) Response duration more than 3 months (n=138); 2) Progression or response duration less than 3 months (n=64). Within both subgroups, the hazard ratio’s for the endpoints were of equal magnitude (.40–.60), indicating that the beneficial effect of Rituximab existed in both subgroups. In conclusion these results demonstrate that the addition of Rituximab to second line of chemotherapy followed by ASCT results in a significant improved FFS, DFS, and OS in patients with relapsed/progressive aggressive CD20+ NHL. Table 1 FFS DFS OS *: 2 years estimate DHAP-arm* 21% 46% 48% R-DHAP arm* 52% 82% 62% Hazard ratio .40 .32 .61 p-value log rank test <0.001 0.003 0.03

Front-Line FLAG-IDA and Nove-HiDAC Chemotherapy Improves Overall Survival (OS) and Complete Remission Rates (CR) for Patients with Secondary or Therapy-Related AML Compared to 3&7

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4893-4893
Author(s):  
Sita D. Bhella ◽  
Eshetu G Atenafu ◽  
Andre C Schuh ◽  
Mark D. Minden ◽  
Aaron D. Schimmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Invasive Aspergillosis ◽  
Myeloproliferative Neoplasm ◽  
Rank Test ◽  
P Value ◽  
Front Line ◽  
First Line ◽  
Poor Risk

Abstract Background: Therapy for patients (pts) with high risk AML remains unsatisfactory. Retrospective studies have demonstrated activity of fludarabine, cytarabine, GCSF and idarubicin (FLAG-IDA) and of mitoxantrone, etoposide and cytarabine (NOVE-HiDAC) as salvage therapy in pts with relapsed or refractory AML. A recent randomized trial indicated high complete remission (CR) rates with improved relapsed-free survival when FLAG-IDA is administered as frontline induction therapy (Burnett et al. J Clin Oncol 2013). Since 01/2011, we have used FLAG-IDA as a first line therapeutic option in pts with high risk AML (poor risk cytogenetics, antecedent myeloproliferative neoplasm or myelodysplastic syndrome, and/or therapy-related AML) in an attempt to improve CR rates and permit more patients with AML to advance to allogeneic hematopoietic cell transplantation (alloHCT). Prior to 2011, either 3&7 or NOVE-HiDAC was used as first line therapy in patients with AML. Methods: We conducted a retrospective review of consecutive patients with high risk AML treated with front-line (a) FLAG-IDA between 01/2011 to 03/2015, (b) NOVE-HiDAC from 01/2006 to 12/2014, or (c) 3&7 from January 01/2011 to 12/2014 at the Princess Margaret Cancer Centre, to determine the CR rates and overall survival (OS) associated with the different regimens. Results: Patients characteristics are in Table 1. Fifty-two, 32, and 30 pts received FLAG-IDA, NOVE-HiDAC or 3&7 as first induction, respectively. Patients receiving FLAG-IDA had more high-risk features (i.e. complex cytogenetics, more azacytidine failures) compared to those receiving 3&7. Overall CR rate (i.e. CR + [CRi] + [CRp]) with FLAG-IDA, NOVE-HiDAC, and 3&7 respectively was 86% (n=42/49), 84% (n=21/25) and 50% (n=13/26), respectively. Median CR duration, censored at time of transplant, for pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 was 3 mos (0.5-15), 3.5 mos (1-9) and 5.5 mos (0.5-42), respectively. OS at 1 year with FLAG-IDA, NOVE-HiDAC and 3&7 was 61% (95% CI, 41% -75%), 55% (95% CI, 34%-72%) and 21.6% (95% CI, 7.4%-40.7%), respectively (log-rank test p-value=0.0076). On subgroup analysis, there was no statistical difference in OS for pts ≥70 years. Of those with a donor identified, 35% (n=13/37), 73% (n=11/15) and 29% (n=5/17) of pts who were treated with FLAG-IDA, NOVE-HiDAC and 3&7 underwent an alloSCT, respectively. Pts with sAML may have had a higher transplant rate due to donor searches initiated earlier. Probable and possible invasive aspergillosis infections in pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 were 50%, 34% and 33% respectively. Institution of earlier bronchoscopies led to increased fungal detection in the FLAG-IDA group. Median length of stay and ICU transfers were similar between groups. Induction deaths were secondary to sepsis, respiratory failure, invasive aspergillosis, and hemorrhage; these were similar across groups. Two pts receiving NOVE-HiDAC, with prior MPN, died of progressive splenomegaly and liver failure. Conclusions: Toxicities associated with frontline FLAG-IDA and NOVE-HIDAC induction are acceptable. FLAG-IDA and NOVE-HiDAC induction can result in durable CR, permitting patients with high risk AML to proceed to alloSCT and providing more favourable survival rates than frontline 3&7. Randomized studies are needed to confirm these findings for pts with poor-risk sAML and tAML. Table 1. Patient Characteristics FLAG-IDA(2013-2015) NOVE-HiDAC(2006-2014) 3&7(2011-2014) N=52 N=32 N=30 Median Age,y (range) Age <70 Age ≥ 70 Sex (M:F) 59.5 (21-76) 47 (90%) 5 (10%) 25:27 54.5 (24-74) 31 (97%) 1 (3%) 18:14 61.5 (20-78) 21 (70%) 9 (30%) 23:7 Cytogenetics by MRC Classification Good Intermediate Poor Not available 0 (0%) 25 (48%) 23 (44%) 4 (8%) 0 (0%) 18 (56%) 9 (28%) 5 (16%) 0 (0%) 20 (67%) 6 (20%) 4 (13%) Molecular (Pts ≤70 y with normal karyotype) FLT3-NPM1+ FLT3+ NPM1+ FLT3+ NPM1- FLT3-NPM1- 1/11 (9%) 5/11 (45%) 2/11 (18%) 3/11 (27%) 0/7 (0%) 2/7 (29%) 1/7 (14%) 4/7 (57%) 0/7 (0%) 1/7 (14%) 0/7 (0%) 6/7 (86%) WBC (x 109/L) (range) 5.15 (0.6 -239) 13 (1.3-182.4) 3.2 (0.7-164) sAML IBMFS MPN MDS Prior AZA 27 (52%) 0/27 (0%) 10/27 (37%) 17/27 (63%) 9/17 (53%) 29 (91%) 1/29 (4%) 15/29 (51%) 13/29 (45%) 2/13 (15%) 20 (67%) 2/20 (10%) 0/20 (0%) 18/20 (90%) 5/18 (28%) Therapy-Related (%) 14 (27%) 6 (19%) 15 (50%) De Novo AML with Complex Cytogenetics FLT3+ Other (ie MLL) 15 (29%) 7/15 (47%) 5/15 (33%) 3/15 (20%) 0 (0%) 0 (0%) Donor Identified (%) 37(71%) 16(50%) 17(57%) Disclosures Gupta: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.

Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA671-LBA671 ◽  
Author(s):  
Karen A. Gelmon ◽  
Frances Boyle ◽  
Bella Kaufman ◽  
David Huntsman ◽  
Alexey Manikhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Her2 Status ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

LBA671 Background: The relative efficacy of L vs T when combined with Tax chemotherapy in the first-line setting of metastatic breast cancer (BC) is unknown. Methods: MA.31 compares Tax-based therapy, paclitaxel 80mg/m2 wkly or docetaxel 75mg/m2 3 wkly for 24 wks in combination with L or T. The L dose was 1,250 mg po daily with Tax followed by 1,500 mg daily (LTax/L). After a loading dose, the T dose was 2 mg/kg wkly or 6 mg/kg 3 wkly + Tax followed by T 6 mg/kg 3 wkly (TTax/T). Stratification was by prior neo/adjuvant HER2 therapy, prior neo/adjuvant Tax, planned Tax (paclitaxel vs docetaxel), and liver metastases. The primary endpoint is ITT progression-free survival (PFS), defined as time from randomization to objective progressive disease based on RECIST criteria or death from any cause. The protocol-specified IA was performed after observing 333 PFS events; the trial was to stop if the 2-sided p-value from the stratified log-rank test was less than 0.03. The NCIC CTG’s independent DSMC reviewed IA results and recommended disclosure because the superiority boundary was crossed. A secondary analysis utilized central laboratory-confirmed HER2 + status. Results: Between July 17 2008 and Dec 1 2011, 652 pts were accrued. Data from 636 pts (525 HER2 centrally confirmed) were included in the IA with clinical cutoff date of Nov 7 2011 and database lock of Apr 13 2012. Median follow-up was 13.6 mos, 12.9 mos for LTax/L pts and 14.0 mos for TTax/T patients. In the ITT analysis, PFS was inferior with LTax/L compared to TTax/T hazard ratio (HR) =1.33; 95% CI 1.06-1.67; p=0.01. LTax/L had median PFS 8.8 mos (95% CI 8.3-10.6) compared to TTax/T 11.4 mos (95% CI 10.8-13.7). PFS in the centrally confirmed HER2+ had HR 1.48 (95%CI 1.15-1.92; p=0.003) (LTax/L to TTax/T). No difference in overall survival was detected (LTax/L to TTax/T) HR= 1.1 (95% CI 0.75-1.61; p=0.62). More grade 3-4 diarrhea and rash was observed with LTax/L (p<0.001). Conclusions: LTax/L therapy is associated with a shorter PFS compared to TTax/T as first line therapy for HER2+ metastatic BC. ClinicalTrials.gov: NCT00667251. CCSRI grant: 021039. Supported by GlaxoSmithKline.

Efficacy of pertuzumab in combination with trastuzumab and a taxane in first-line treatment for metastatic breast cancer (MBC): A multicenter, retrospective, observational study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12504-e12504 ◽  
Author(s):  
Teresa Gamucci ◽  
Lucia Mentuccia ◽  
Isabella Sperduti ◽  
Alain Gelibter ◽  
Loretta D'Onofrio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Observational Study ◽  
Real World ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Rank Test ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

e12504 Background: Pertuzumab (P) , Trastuzumab (T) and Docetaxel (D) is standard first-line treatment in patients (pts) with HER2 + metastatic breast cancer (MBC). This multicenter retrospetive observational study was performed to evaluate the activity of P and T in combination with D or Paclitaxel (Tx) in real world HER2 + MBC pts. Methods: We identified HER2 + MBC pts treated with P, T and D or Ptx optionally followed by P, T and endocrine therapy (ET) maintenance in hormone positive (HR+) BC, in 17 Italian cancer centres between 09/2012 and 08/2016. Overall Survival (OS) and Progression Free Survival (PFS) were calculated by the Kaplan-Meier product-limit method. Log-rank test was used to assess differences between subgroups. Results: 191 pts were included in our analysis. Pts characteristics: median age 54 years (range 29-80); PS 0 in 127 (67%) pts and PS 1 in 54 (28%); 107 (56%) had visceral metastases (mts), 23 (12%) only bone mts and 28 (15%) brain mts, 130 (68%) were ER/PgR +. 76 pts (40%) were metastatic at diagnosis; 148 (78) were treated with D while 43 (22%) with Tx. The ORR was 78% (CI 95% 72-84), RC 18% and RP 60%, only 10 (5%) had PD. To date, of the 54 pts treated with ET maintenance, 26% had a further improvement of response (7 pts had RC). At median follow-up of 17 months (mo) (range 6- 52), median PFS was 20 mo (95% CI 14-26) and median OS at 2 years was 80%. No differences in PFS were found for age (p = 0.92), PS (p = 0.18), receptor status (p = 0.57), visceral mts (p = 0.54) and chemotherapy (cht) type (p = 0.47), whereas number of mts site (1 vs > 1) affected PFS (28 vs 16 mo, p = 0.002). Moreover median PFS in naïve pts and in pts pretreated with only cht was 28 mo (95% CI, 20-36) and 27 mo (95% CI, 16-38) respectively, whereas in pts pretreated with T it was 12 mo (95% CI 16-38 p 0.002). In HR+ pts ET maintenance together with P and T had an impact on PFS (28 vs 15 mo, p = 0.01). Conclusions: Our analysis confirms, in real world HER2 MBC pts, the efficacy of P, T and a taxane combination in first line treatment; in this population PFS was shorter in pts pretreated with T. ET maintenance in association with P and T in HR+ pts improved PFS. Data collection is ongoing and update results will be presented.

Activity of second line axitinib in metastatic renal cell carcinoma (mRCC) patients treated with sunitinib: Results from SAX Italian real world trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16054-e16054
Author(s):  
Sabrina Rossetti ◽  
Francesco Jacopo Romano ◽  
Carmine D'Aniello ◽  
Carla Cavaliere ◽  
Salvatore Pisconti ◽  
...  
Keyword(s):  
Real World ◽  
Medical Records ◽  
Kinase Inhibitor ◽  
Univariate Analysis ◽  
P Value ◽  
World Population ◽  
Second Line ◽  
First Line ◽  
Primary Endpoints ◽  
Significant Difference

e16054 Background: Axitinib, a selective tyrosine kinase inhibitor (TKI), is currently approved for the treatment of mRCC after failure of prior treatment with sunitinib or cytokine, according to AXIS trial results. The best sequence hasn’t been established: both axitinib and everolimus (a mTOR inhibitor) are viable therapeutic options, although recently immunotherapy agents entered this setting. This Italian multi-institutional retrospective analysis evaluated outcomes of Axitinib in exclusive sequence after sunitinib in second line treatment of mRCC Methods: Medical records of 148 patients treated with Axitinib from 21 Italian Oncology Centers were retrospectively assessed: PFS, OS, ORR DCR, and safety profile of axitinib were primary endpoints. Results: Median PFS and OS were 7.14 and 15.5 months, respectively. Overall, axitinib at standard schedule of 5 mg bid, was well tolerated, with no grade 4 toxicity event. Most common adverse events were hypertension (26% of the cases), fatigue (50 %), hypothyroidism (18%). At univariate analysis, when patients were stratified by Heng score, mPFS was 5.8, 7.0 and 9.0 months according to poor, intermediate and favourable risk group, respectively. When stratified by median duration of prior sunitinib therapy (≥ 13,1 mo vs < 13,1 mo), there was a statistically significant difference in PFS with 8.8 vs 6.3 months, respectively. Disease control rate (DCR) to previous sunitinib treatment was associated to longer PFS with axitinib ( 8.0 months vs4.0 months). The sequence sunitinib-axitinib was well tolerated, with a mOS of 41 months. At multivariate analysis, prognostic factors for progression were gender (p-value = 0,006), DCR to axitinib (p < 0,0001) and to previous sunitinib (p = 0,041); DCR to axitinib (p = < 0,0001), nephrectomy (p = 0,002) and Heng score (p = 0,025) independently affected overall survival. Conclusions: The preliminary SAX results in the real world population are consistent with available literature. The study confirms that Axitinib is effective and safe in routine clinical practice, and its efficacy seems to be greater in patients who most benefited from first-line sunitinib.

Real-world evidence in patient-related outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate plus prednisone (AA+P).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 196-196 ◽  
Author(s):  
Geoffrey Gotto ◽  
Vincent Fradet ◽  
Darrel Drachenberg ◽  
Robert Sabbagh ◽  
Ricardo A. Rendon ◽  
...  
Keyword(s):  
Real World ◽  
Metastatic Cancer ◽  
Abiraterone Acetate ◽  
Cognitive Status ◽  
Continuous Variables ◽  
Absolute Change ◽  
The Mean ◽  
Clinically Significant ◽  
Moca Score ◽  
Over Time

196 Background: Oral androgen biosynthesis inhibitor, abiraterone acetate plus prednisone (AA+P), has shown to improve survival and patient-related outcomes (PROs) in clinical trials. The COSMiC study (Canadian Observational Study in Metastatic Cancer of the Prostate; ClinicalTrials.gov: NCT02364531) set out to prospectively amass real-world data on mCRPC patients (pts) managed with AA+P in communities within Canada. Here, we report the interim analysis of their PROs. Methods: At planned data cutoff in Sept 2017 after a median follow-up of 33.8 months, 264 pts were enrolled in 39 sites across Canada. Their FACT-P (Functional Assessment of Cancer Therapy – Prostate) and MoCA (Montreal Cognitive Assessment) were evaluated at baseline as well as at weeks 12, 24, 48 and 72 after AA+P initiation. A 10-point decrease denotes clinically significant degradation in FACT-P and a total MoCA score of > = 26 is considered normal. Descriptive analysis was utilized with continuous variables. Changes from baseline were summarized using mean (SD). Results: At a median age of 77 among 264 pts, 230, 185, 110 and 63 pts were available for analysis at their week 12, 24, 48, and 72 assessments respectively. The mean baseline FACT-P total score was 111.2 (19.44) with a < 3-point absolute change from baseline at subsequent assessments, denoting no clinically significant change in functional status over time. The mean baseline MoCA score was 25.2 (4.50), yet all subsequent assessments scored above 26 and a mean absolute change from baseline of < 1, showing an absence of cognitive decline over time. PSA value was available for 221 pts, 64.3% (142/221) and 34.4% (76/221) achieved a PSA decline of > 50% and 90% respectively. All-grade treatment-related adverse events were reported in 63 pts, with 11% who have had AA+P discontinuation or interruption. Conclusions: COSMiC represents the largest Canadian mCRPC cohort treated with AA+P with real world prospective evaluation of PROs. This data demonstrated the maintenance in quality of life and cognitive status over the course of the study, and underscores the importance of PRO utilization in this complex patient population. Clinical trial information: NCT02364531.

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