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

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.

ESMO Open ◽  
2021 ◽  
Vol 6 (2) ◽  
pp. 100065
Author(s):  
G. Jeryczynski ◽  
M. Antlanger ◽  
F. Duca ◽  
C. Binder-Rodriguez ◽  
T. Reiter ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  

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


Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 178
Author(s):  
Alessandro Nota ◽  
Silvia Caruso ◽  
Shideh Ehsani ◽  
Gianmaria Fabrizio Ferrazzano ◽  
Roberto Gatto ◽  
...  

Background and objectives: The aim of this study is to evaluate mandibular elevator muscles activity and pain on palpation in the early stages of orthodontic treatment with clear aligners using surface electromyography (sEMG). Materials and methods: Surface electromyography (sEMG) activity and pain level on muscle palpation of masseter and anterior temporalis muscles were recorded in a sample of 16 adult subjects (aged 18–32 years; mean 22.5 +/− 3.5 SD) undergoing orthodontic treatment with clear aligners before the treatment (T0), after 1 month of treatment (two clear aligners) (T1), and after 3 months of treatment (T2) (six clear aligners). A chi-square test for nominal data, a Friedman test, and a Wilcoxon-signed rank test as post hoc analysis were applied. Results: No statistically significant differences in muscular pain were observed. At T1, the sEMG activity of masseter muscles at mandibular rest position showed a statistically significant reduction, but after 3 months (T2), the data appeared similar to T0 (p = 0.03 and p = 0.02). Conclusions: During the treatment with clear aligners, subjects could experience an initial reduction in the masseter basal activity after 1 month of treatment. This effect tends to decrease to baseline levels after 3 months of therapy.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8561-8561
Author(s):  
Eric S. Nadler ◽  
Anupama Vasudevan ◽  
Kalatu Davies ◽  
Yunfei Wang ◽  
Ann Johnson ◽  
...  

8561 Background: Atezolizumab plus chemotherapy was the first CIT combination regimen approved for 1L treatment of ES-SCLC in 2019. This study investigated patient characteristics and treatment patterns for patients with ES-SCLC receiving this regimen in the real-world community oncology setting. Methods: This was a retrospective study including adult patients diagnosed with ES-SCLC between 01-Oct-2018 (after IMpower 133 publication in NEJM Sep-2018) and 31-Dec-2019, with follow-up through 31-March-2020 using The US Oncology Network electronic health records data. Descriptive analyses of patient characteristics and treatment patterns were conducted, with Kaplan-Meier (K-M) methods used to assess time to treatment discontinuation (TTD) and time to next treatment/death (TTNT). Results: Of the 408 patients included in this study, 267 (71.4%) received atezo+carboplatin+etoposide (Atezo+Chemo), 80 (21.4%) received carboplatin+etoposide (Chemo only) and the rest received other regimens. The Atezo+Chemo patients in the real-world cohort compared with the IMpower 133 trial (n = 201) were older (median age 68 vs. 64 years) and included fewer males (45% vs. 64%), fewer white race (73% vs. 81%), more patients with brain metastases at baseline (23% vs. 9%), and more patients with worse ECOG (2/3) performance-status score (24% vs. 0%). The median follow-up, TTD, and TTNT in months (mo) for the real-world cohort are presented in the table alongside the best comparable measures reported for the trial. Conclusions: Most patients in this real-world ES-SCLC cohort received the Atezo+Chemo regimen in the 1L setting. While the follow-up was much shorter and patients had worse baseline characteristics (age, brain metastases, ECOG) in the real-world setting compared to the IMpower 133 trial, the real-world median TTD in this descriptive analysis was found to be in line with the median duration of treatment in the trial. Further research with longer follow-up comparing the real-world effectiveness of the CIT and chemo regimens is needed.[Table: see text]


2008 ◽  
Vol 78 (5) ◽  
pp. 935-940 ◽  
Author(s):  
Davide Mirabella ◽  
Raffaele Spena ◽  
Giovanni Scognamiglio ◽  
Lombardo Luca ◽  
Antonio Gracco ◽  
...  

Abstract Objective: To test the hypothesis that bonding with a blue light-emitting diode (LED) curing unit produces no more failures in adhesive-precoated (APC) orthodontic brackets than bonding carried out by a conventional halogen lamp. Materials and Methods: Sixty-five patients were selected for this randomized clinical trial, in which a total of 1152 stainless steel APC brackets were employed. In order to carry out a valid comparison of the bracket failure rate following use of each type of curing unit, each patient's mouth was divided into four quadrants. In 34 of the randomly selected patients, designated group A, the APC brackets of the right maxillary and left mandibular quadrants were bonded using a halogen light, while the remaining quadrants were treated with an LED curing unit. In the other 31 patients, designated group B, halogen light was used to cure the left maxillary and right mandibular quadrants, whereas the APC brackets in the remaining quadrants were bonded using an LED dental curing light. The bonding date, the type of light used for curing, and the date of any bracket failures over a mean period of 8.9 months were recorded for each bracket and, subsequently, the chi-square test, the Yates-corrected chi-square test, the Fisher exact test, Kaplan-Meier survival estimates, and the log-rank test were employed in statistical analyses of the results. Results: No statistically significant difference in bond failure rate was found between APC brackets bonded with the halogen light-curing unit and those cured with LED light. However, significantly fewer bonding failures were noted in the maxillary arch (1.67%) than in the mandibular arch (4.35%) after each light-curing technique. Conclusions: The hypothesis cannot be rejected since use of an LED curing unit produces similar APC bracket failure rates to use of conventional halogen light, with the advantage of a far shorter curing time (10 seconds).


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 275-275
Author(s):  
Carla Pires Amaro ◽  
Michael J Allen ◽  
Jennifer J. Knox ◽  
Erica S Tsang ◽  
Howard John Lim ◽  
...  

275 Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG >1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC. [Table: see text]


2020 ◽  
Author(s):  
Chao Zhang ◽  
Wen An ◽  
Yuen Tan ◽  
Huimian Xu

Abstract Background CKLF Like MARVEL Transmembrane Domain Containing 6 (CMTM6) is involved in the epigenetic regulation of genes and tumorigenesis. Programmed cell death ligand 1 (PD-L1) is closely related to the prognosis of some human cancers. CMTM6 is a key regulator of PD-L1 in many cancers. The purpose of this study was to investigate the expressions of these proteins in gastric cancer and the correlations with clinicopathological features and survival. Methods The expression levels of CMTM6 and PD-L1 were examined in 185 gastric cancer specimens by immunohistochemistry. Chi-square test was used to analyze the relationship between CMTM6 and PD-L1 expressions and clinicopathological characteristics. Kaplan-Meier method and log-rank test were used to analyze the survival data of patients.Results The positive expression rates of CMTM6 and PD-L1 were 78.38% (145/185) and 75.68% (140/185), respectively. High expression of CMTM6 and PD-L1 was correlated with Borrmann type ( P < 0.001), N stage ( P = 0.002), peritoneal metastasis ( P = 0.007) and TNM stage ( P = 0.038). The expression of CMTM6 and PD-L1 in gastric cancer tissues was positively correlated (Pearson's coefficient test, r = 0.260; P < 0.001). High expression of CMTM6 was correlated with poor prognosis (HR = 1.668; 95% CI = 1.032–2.695; P = 0.037). High expression of both CMTM6 and PD-L1 could be used as an independent factor for overall survival (HR = 1.554; 95% CI = 1.011–2.389; P = 0.044). Conclusions The combined detection of CMTM6 and PD-L1 may be used as an indicator for judging the prognosis of gastric cancer.


2019 ◽  
Vol 130 (6) ◽  
pp. 1877-1888
Author(s):  
Mark G. Bigder ◽  
Sandeep Krishnan ◽  
E. Francis Cook ◽  
Anthony M. Kaufmann

OBJECTIVEPatients with multiple sclerosis (MS)–associated trigeminal neuralgia (TN) have higher recurrence and retreatment rates than non-MS patients. The optimal management strategy and role for microsurgical rhizotomy (MSR) for MS-TN remains to be determined. The aim of this study was to report time to treatment failure (TTF) and pain scores following MSR compared to percutaneous and Gamma Knife procedures.METHODSTime to treatment failure was analyzed after MSR (n = 14) versus prior procedures (n = 53) among MS-TN patients. Kaplan-Meier curves and log-rank test were utilized to compare TTF after MSR versus prior procedures using the same cohort of patients as their own control group. Subsequent analysis compared TTF after MSR to TTF after 93 other procedures among a second cohort of 18 MS-TN patients not undergoing MSR. BNI pain scores were compared between MSR and other procedures among the MS-TN cohort using a chi-square test.RESULTSTTF was significantly longer after MSR than after other procedures in the MSR cohort (median TTF 79 vs 10 months, respectively, p < 0.0001). Similarly, TTF was longer after MSR than after prior procedures in the non-MSR cohort (median TTF 79 vs 13 months, respectively, p < 0.001). MSR resulted in a higher proportion of excellent pain scores when compared to other procedures in the non-MSR cohort (77% vs 29%, p < 0.001). Probability of treatment survival was higher after MSR than after other procedures at all time points (3, 6, 12, 24, 36, and 48 months). There were no deaths or major complications after MSR.CONCLUSIONSTTF was significantly longer following MSR compared to prior procedures in MS-TN patients. Additionally, a higher proportion of patients achieved excellent BNI pain scores after MSR.


2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-085
Author(s):  
Belqis El Ferjani ◽  
Sheenu Chandwani ◽  
Meita Hirschmann ◽  
Seydeh Dibaj ◽  
Emily Roarty ◽  
...  

Background: NSCLC is the leading cause of cancer-related mortality worldwide. Recently reported clinical trials have firmly established the role of PD-1 and PD-L1 inhibitors in the treatment of patients (pts) with metastatic NSCLC (mNSCLC). We have established the prospective, observational, real-world Advanced Non-Small Cell Lung Holistic Registry (ANCHoR) to understand how the advent of immunotherapy impacts treatment choices and clinical outcomes. Objectives: The aim of this analysis is to measure the impact of immunotherapy on the treatment choice for the first-line treatment of mNSCLC and to determine the link between PD-L1 expression and the treatment choices made in routine clinical practice at the MD Anderson Cancer Center (MDA). Methods: From May 1, 2017, to June 30, 2018, English-speaking pts with mNSCLC at MDA who provided written informed consent were enrolled in ANCHoR and longitudinally followed. The PD-L1 testing rates were captured and the treatment decisions made were also captured and tabulated. The time of data cutoff for this study is June 30, 2018. Results: Of the 296 pts enrolled in the registry at the time of data cutoff, there were 49.7% males, 82.1% white, 45.9% ≥65 years old, 69.3% smokers, 83.1% with an initial stage IV diagnosis, 87.2% with nonsquamous histology, 36.1% with bone metastasis, 29.4% with brain metastasis, 43.2% with 0–1 performance status, and 21.6% with a known EGFR or ALK mutation. A total of 233 pts had been tested for PD-L1 (78.7%). Predominant reasons for not testing (63 pts) include not having available tissue (26 pts) or the test was not requested by the physician (31 pts). As of June 30, 2018, 38.5% of patients received immunotherapy as first-line therapy either as a single agent (18.9%, 56 pts) or in combination with chemotherapy (19.6%, 58 pts). Only 35.8% of the patients received platinum doublet chemotherapy alone. Two pts received chemotherapy combined with an anti-angiogenesis agent (0.68%). Targeted therapy was utilized either as a single agent (20.6%) or in combination with immunotherapy (2.4%). Conclusion: Immunotherapy is now utilized as a single agent or in combination in more than one-third of patients with mNSCLC. These numbers are expected to increase as data from recently reported studies get incorporated into common clinical practice. Compared to historic experience, there has been a dramatic decline in the use of chemotherapy with an anti-angiogenesis agent.


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