Assessment of ethnic difference in the incidence of thrombocytopenia induced by trastuzumab emtansine (T-DM1): A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15096-e15096
Author(s):  
Jingyi Zhang ◽  
Yaning Yang ◽  
Ru Chen ◽  
Shanshan Chen ◽  
Jiayu Wang ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Data Extraction ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Cancer Type ◽  
Trastuzumab Emtansine ◽  
Cancer Disease ◽  
Asian Patients ◽  
Grade 3

e15096 Background: Trastuzumab emtansine (T-DM1) has been proved its value and efficacy in advanced metastatic cancer disease as well as in the adjuvant setting. However, there is an increasing concern in T-DM1-induced thrombocytopenia (TCP), which also showed difference of incidence in races. This meta-analysis, combining available data from all single-agent T-DM1 studies to date, aimed to evaluate the incidence of treatment-related thrombocytopenia of T-DM1 and the differences between Asian and non-Asian patients. Methods: We conducted a systematic search of the relevant published clinical studies of T-DM1 that reported safety profile including thrombocytopenia, from 1980 to March of 2020 using PubMed, Embase, and the Cochrane database. Screening and data extraction were conducted by two independent reviewers. Pooled-effect estimates calculated with fixed-effects or random-effects model were expressed as incidence with 95% CIs. Results: A total of 29 studies involving 6188 patients were included. The incidence of all-grade thrombocytopenia in Asian patients was 0.39 (95%CI 0.11-0.67) and 0.29 (95%CI 0.23-0.35) in non-Asian patients. And the incidence of the grade 3 or higher thrombocytopenia in Asians was 0.20 (95%CI 0.10-0.29), in non-Asians was 0.02 (95%CI 0.01-0.03). Gastrointestinal cancer type and the dose of 2.4 mg/kg Q3W T-DM1 treatment were both associated with the higher incidence of grade 3 or higher thrombocytopenia. Conclusions: Asian patients have the higher risk of thrombocytopenia induced by T-DM1. Clinicians should have an awareness of careful observation in platelet counts when patients receive T-DM1 therapy.

scholarly journals Ramucirumab Safety in East Asian Patients: A Meta-Analysis of Six Global, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trials

2018 ◽  
pp. 1-12
Author(s):  
Chia-Jui Yen ◽  
Kei Muro ◽  
Tae-Won Kim ◽  
Masatoshi Kudo ◽  
Jin-Yuan Shih ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Meta Analysis ◽  
East Asian ◽  
Phase Iii ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Asian Patients ◽  
Relative Risks ◽  
Phase Iii Trials ◽  
Grade 3

Purpose Several ramucirumab trials have reported a higher incidence of selected adverse events (AEs) in East Asian (EA) patients with cancer versus non-EA patients. A meta-analysis was conducted across six completed phase III trials to establish the safety parameters of ramucirumab in EA compared with non-EA patients. Materials and Methods Six global, randomized, double-blind, placebo-controlled, phase III registration trials investigating ramucirumab were assessed. Relative risks (RRs) and 95% CIs were calculated for selected all-grade and grade ≥ 3 AEs using fixed-effects and mixed-effects models. Ratio of RR and number needed to harm were calculated for AEs (all grade and grade ≥ 3) between EA and non-EA patients. Results Of 4,996 randomly assigned patients receiving ramucirumab or placebo, 802 (16.1%) were EA (ramucirumab, n = 411; placebo, n = 391) and 4,194 were non-EA (ramucirumab, n = 2,337; placebo, n = 1,857). Patient baseline characteristics were generally balanced between treatment arms in EA and non-EA patients, excluding sex and body weight. Grade ≥ 3 AEs possibly associated with ramucirumab, which were increased in EA versus non-EA patients, included neutropenia (42.1% v 25.5%, respectively) and proteinuria (3.9% v 0.6%, respectively). There was an increase in the RR of several grade ≥ 3 AEs, including hypertension and proteinuria, in ramucirumab-treated EA and non-EA patients compared with placebo. The ratio of RR revealed no significant differences between EA and non-EA patients for all-grade and grade ≥ 3 AEs. Conclusion Despite the enhanced propensity of selected AEs in EA patients relative to non-EA patients, there were no substantial differences in the RR for AEs possibly associated with ramucirumab in these phase III trials.

A Systematic Review and Meta-Analysis about the Effect of Bisphosphonates on the Risk of Skeletal-Related Event in Men with Prostate Cancer

2020 ◽  
Vol 20 (13) ◽  
pp. 1604-1612
Author(s):  
Congcong Wu ◽  
Hua Jiang ◽  
Jianghua Chen
Keyword(s):  
Prostate Cancer ◽  
Fixed Effects ◽  
Data Extraction ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Control Group ◽  
Fixed Effects Model ◽  
Related Event ◽  
Mineral Density ◽  
Skeletal Related Event

Background: Although the adjuvant therapy of bisphosphonates in prostate cancer is effective in improving bone mineral density, it is still uncertain whether bisphosphonates could decrease the risk of Skeletal- Related Event (SRE) in patients with prostate cancer. We reviewed and analyzed the effect of different types of bisphosphonates on the risk of SRE, defined as pathological fracture, spinal cord compression, radiation therapy to the bone, surgery to bone, hypercalcemia, bone pain, or death as a result of prostate cancer. Methods: A systemic literature search was conducted on PubMed and related bibliographies. The emphasis during data extraction was laid on the Hazard Ratio (HR) and the corresponding 95% Confidence Interval (CI) from every eligible Randomized Controlled Trial (RCT). HR was pooled with the fixed effects model, and preplanned subgroup analyses were performed. Results: 5 RCTs (n = 4651) were included and analyzed finally after screening 51 articles. The meta-analysis of all participants showed no significant decrease in the risk of SRE when adding bisphosphonates to control group (HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536) with low heterogeneity (I2 = 0.0% (d.f. = 4) p = 0.679). There was no significant improvement on SRE neither in the subgroups with Metastases (M1) or Castration-Sensitive Prostate Cancer (CSPC) (respectively HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536, I2 = 0.0% (d.f. = 4) p = 0.679; HR = 0.954, 95% CI = 0.837 - 1.088, p = 0.484, I2 = 0.0% (d.f. = 3) p = 0.534). Conclusion: Our study demonstrated that bisphosphonates could not statistically significantly reduce the risk of SRE in patients with prostate cancer, neither in the subgroups with M1 or CSPC.

scholarly journals A Comparative Meta-Analysis of the Effects of Concussion on a Computerized Neurocognitive Test and Self-Reported Symptoms

2017 ◽  
Vol 52 (9) ◽  
pp. 834-846 ◽  
Author(s):  
Bara Alsalaheen ◽  
Kayla Stockdale ◽  
Dana Pechumer ◽  
Steven P. Broglio ◽  
Gregory F. Marchetti
Keyword(s):  
Test Performance ◽  
Fixed Effects ◽  
Data Extraction ◽  
Meta Analysis ◽  
Cognitive Testing ◽  
Cognitive Test ◽  
Fixed Effects Model ◽  
Symptom Scale ◽  
Additional Information ◽  
Neurocognitive Test

Context:  Meta-analyses examining construct-specific cognitive impairment concurrently with self-reported symptoms postconcussion are sparse. Objective:  To review the literature on the effects of concussion on construct-specific neurocognitive declines and to compare them with self-reported symptoms before 1 week and between 1 and 3 weeks postconcussion. Data Sources:  Relevant studies in PubMed, CINAHL, and PsycINFO published from January 1, 1999 through November 30, 2015. Study Selection:  Studies were included if participants completed the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) before and after concussion and if test performance and Postconcussion Symptom Scale (PCSS) scores were reported at both times. Data Extraction:  After reviewing the full texts, we extracted data from 17 studies consisting of 29 independent samples; therefore, this meta-analysis consisted of 1777 unique participants. Data Synthesis:  The Hedges g effect size (ES) was estimated. A random-effects or fixed-effects model was used based on heterogeneity findings. When heterogeneity was present, we used meta-regression to assess unexplained between-studies variance. Within the first week of injury, the ESs were small to moderate for cognitive declines, ranging from −0.43 (95% confidence interval [CI] = −0.52, −0.35) to −0.67 (95% CI = −0.77, −0.58), and large for the PCSS score (Hedges g = −0.81; 95% CI = −0.91, −0.71). After 1 week, the ESs for cognitive declines (Hedges g range = −0.25 [95% CI = −0.35, −0.15] to −0.37 [95% CI = −0.55, −0.19]) and PCSS score (Hedges g = −0.38; 95% CI = −0.53, −0.22) were also small. Within 2 weeks of injury, PCSS score and time since injury weakly moderated the cognitive ES. Conclusions:  When a neurocognitive test was administered within 1 week of injury, the ES was larger for self-reported symptoms than for ImPACT scores generated at the same session. After 1 week of injury, the ESs for ImPACT and PCSS scores were comparable. If the athlete reports symptoms within 1 week of injury, administering a cognitive test does not appear to offer additional information to the clinician. However, if the athlete does not report symptoms postconcussion, cognitive testing may inform the clinical management of the injury.

scholarly journals Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for Patients With Advanced Breast Cancer: a Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng
Keyword(s):  
Breast Cancer ◽  
Randomized Controlled Trials ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Parp Inhibitors ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Grade 3

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P＜0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.

scholarly journals Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592090540 ◽  
Author(s):  
Victor H. F. de Jesus ◽  
Marcos P. G. Camandaroba ◽  
Vinicius F. Calsavara ◽  
Rachel P. Riechelmann
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
Advanced Pancreatic Adenocarcinoma

Background: There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity. Methods: We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions. Results: Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 versus 8.4%; p = 0.038) and DCR (53.5 versus 30.5%; p < 0.001) compared with single-agent gemcitabine. Median PFS ranged from 1.9 to 6.4 months and numerically favored gemcitabine plus nab-paclitaxel. Conclusions: Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421).

Risk of mineralocorticoid excess syndrome with CYP17 inhibitor abiraterone in prostate cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15140-e15140
Author(s):  
Sandy Ann Itwaru ◽  
Arun Gopal ◽  
Omer Bashir ◽  
Joomee Shim ◽  
Xiaolei Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Side Effects ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Abiraterone Acetate ◽  
Fixed Effects Model ◽  
Starting Dose ◽  
Grade 3 ◽  
American Society

e15140 Background: CYP17 inhibitor abiraterone acetate has been used for the treatment of patients with metastatic castration-refractory prostate cancer (CRPC). Hypertension, hypokalemia and edema are the major side effects associated with its use, and may be secondary to the excess of mineralocorticoids due to CYP17 inhibition. We performed a systematic review and meta-analysis of published clinical trials to determine the effect of abiraterone on the development of these side effects. Methods: Databases including Pubmed (July, 1966 to July, 2011), Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings from 2008 to 2011 were searched to identify relevant studies. Eligible studies were prospective clinical trials of patients with prostate cancer receiving abiraterone acetate at the starting dose of 1,000 mg daily with available data on hypertension, hypokalemia and edema. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model. Results: A total of seven studies including 1,387 patients with CRPC were selected for analysis. The incidences of all-grade hypertension, hypokalemia, and edema were 13.3% (95% CI: 8.3 to 20.5%), 31.4 % (95% CI: 12.5-59.5%), and 23.4 % (95% CI: 15.6-33.5%) respectively. The incidences of high-grade (grade 3 and above) toxicity were low, with a rate of 3.6% (95% CI: 2.6-5.1%), 2.8 % (95% CI: 0.9 to 8.2%), and 2.1% (95%CI: 1.3-3.2%) for hypertension, hypokalemia, and edema respectively. The risk of hypertension and edema did not change with and without the addition of prednisone (p=0.48 and p=0.40, respectively); however, the risk of hypokalemia was significantly reduced with the addition of prednisone (p = 0.003). In comparison with prednisone alone, the addition of abiraterone did not increase the risk of hypertension (RR 1.22, 95% CI: 0.82 – 1.83, p=0.31), but significantly increased the risk of edema (RR 1.36, 95% CI: 1.10-1.69, p=0.004) and hypokalemia (RR 2.04, 95% CI: 1.42–2.92, p<0.001). Conclusions: There were differential effects of abiraterone on the development of hypertension, hypokalemia, and edema in patients with advanced prostate cancer. Further studies are recommended for optimal treatment.

Incidence of severe nephrotoxicity with cisplatin vs. non-cisplatin regimens: A meta-analysis with sub-group analyses based on renal eligibility criteria.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15549-e15549
Author(s):  
Arati Dahal ◽  
Brandon Kyle Bellows ◽  
Guru Sonpavde ◽  
Matt D. Galsky ◽  
Neeraj Agarwal
Keyword(s):  
Renal Function ◽  
Fixed Effects ◽  
Literature Search ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Exclusion Criterion ◽  
Eligibility Criteria ◽  
Subgroup Analyses ◽  
Grade 3 ◽  
Re Methods

e15549 Background: Serum Creatinine (SCr) is commonly used to screen patients for eligibility in trials of the nephrotoxic drug cisplatin despite the fact that glomerular filtration rate (GFR) is known to better estimate renal function. The objective of this meta-analysis was to indirectly compare incidence of nephrotoxicity in trials using cisplatin for treatment of solid tumors when renal function was assessed using SCr or GFR for eligibility criteria. Methods: A literature search was conducted in PubMed to identify randomized trials comparing cisplatin to non-cisplatin containing chemotherapy regimens. Studies were included if they were performed from 1990-2010, used SCr or GFR as eligibility criteria, and reported incidence of WHO or NCI grade ≥3 nephrotoxic events for both treatment arms. Review articles, non-randomized trials, observational, phase I, studies without a comparator group, or not reported in English were excluded. The relative risk (RR) of grade ≥3 nephrotoxicity associated with cisplatin vs. non-cisplatin regimens was examined using inverse variance weighted fixed effects (FE) and random effects (RE) methods. Subgroup analyses of studies using SCr, GFR, and either SCr or GFR for screening were performed. Results: The literature search identified 2,359 studies, and 42 studies met all inclusion and exclusion criterion (N=9,521 patients). SCr was used as eligibility criteria in 20 studies (N=4,704), GFR was used by 9 studies (N=1,650), and either SCr or GFR was used by 13 studies (N=3,167). The overall RR for developing nephrotoxicity with cisplatin vs. non-cisplatin treatment was 1.75 (95%CI 1.18-2.58, p=0.005). Results from subgroup analyses showed the RR was 2.60 (95%CI 1.34-5.03, p=0.005) when SCr was used as eligibility criteria compared to 1.50 (95%CI 0.82-2.74, p=0.19) when GFR was used and 1.26 (95%CI 0.55-2.85, p=0.59) when either SCr or GFR was used. Results did not vary between FE and RE methods. Conclusions: Cisplatin based therapy is associated with a significant increase in severe nephrotoxicity. The risk of severe nephrotoxicity is higher in trials that utilize SCr as eligibility criteria compared to those that utilize GFR.

Cisplatin-associated nephrotoxicity in clinical trials using serum creatinine (SCr) versus calculated glomerular filtration rate (GFR) as inclusion criterion: A meta-analysis.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 272-272
Author(s):  
Arati Dahal ◽  
Brandon Kyle Bellows ◽  
Guru Sonpavde ◽  
Matt D. Galsky ◽  
Neeraj Agarwal
Keyword(s):  
Renal Function ◽  
Fixed Effects ◽  
Literature Search ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Inclusion Criteria ◽  
Who Grade ◽  
Increased Risk ◽  
Grade 3 ◽  
Re Methods

272 Background: Treatment with cisplatin (CIS) is associated with increased risk of nephrotoxicity and SCr is commonly used to screen patients for renal dysfunction prior to enrollment in trials using CIS. However, GFR is known to better estimate renal function than SCr. The objective of this trial-level meta-analysis was to indirectly compare incidence of WHO grade ≥3 nephrotoxicity associated with CIS therapy when renal function was assessed using SCr vs. calculated GFR during screening for these trials. Methods: A PubMed literature search was used to identify randomized trials comparing treatment regimens including CIS to those without CIS. Studies were included if they were performed between 1990 and 2005, reported SCr or GFR as inclusion criteria, and reported WHO grade ≥3 nephrotoxic events for both the CIS and non-CIS treatment arms. Studies were excluded if they were review articles, observational, phase 1, non-randomized, did not have a comparator group, or were not reported in English. Inverse variance weighted fixed effects (FE) and random effects (RE) methods were used to estimate the relative risk (RR) associated with CIS vs. non-CIS containing regimens with sub-group analyses of studies using SCr, GFR, and either SCr or GFR for screening. Results: The literature search identified 2359 studies. After exclusion criteria, 549 were reviewed and 24 studies (N=5524 patients) met all inclusion criteria for analysis. Of these, 16 studies used SCr (N=3955), 3 used GFR (N=692), and 5 used SCr or GFR (N=877) for screening. Overall incidence proportion of nephrotoxicity was higher for CIS vs. non-CIS regimens (2.1% vs. 0.7%). Overall RR for CIS vs. non-CIS regimens was 2.49 (95%CI 1.37-4.51, p=0.003). In sub-group analyses, the RR was 2.63 (95%CI 1.29-5.39, p=0.008) for SCr compared to 2.39 (95%CI 0.53-10.64, p=0.26) for GFR and 2.03 (95%CI 0.46-9.02, p=0.35) for either SCr or GFR. The RRs did not differ between the FE and RE methods. Conclusions: This indirect comparison meta-analysis shows CIS is associated with a higher likelihood of nephrotoxicity vs. non-CIS regimens, and may be higher when SCr is used instead of GFR as eligibility criteria.

3-weekly daratumumab-IMiD-dexamethasone is highly efficacious and cost-effective in relapsed/refractory multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19521-e19521
Author(s):  
James Chim ◽  
Vincent Wong ◽  
Elaine AU ◽  
Yok-Lam Kwong
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Cost Effective ◽  
Median Number ◽  
Infusion Reaction ◽  
Immunomodulatory Agents ◽  
Asian Patients ◽  
Best Response ◽  
Rapid Responses ◽  
Grade 3

e19521 Background: Daratumumab (dara) with immunomodulatory agents (IMiD) and dexamethasone (dex) is highly effective in relapsed multiple myeloma (MM). The recommended schedule of dara is weekly for 8 doses, followed by 2-weekly for 8 doses, and then every 4-weekly thereafter. Given the high cost and the long half-life as an antibody, a 3-weekly dosing of dara was used together with IMiD/dexamethasone. Methods: Dara at 16mg/kg was used every 3-weekly with lenalidomide or pomalidomide. Patient achieving best response received single agent IMiD maintenance until disease progression. Results: Fourteen relapsed MM patients were enrolled. One had received weekly dara from a private oncologist, hence was excluded from analysis. Thirteen patients at a median age of 63 years (range: 50-84 years) were studied. The median number of previous therapies was 2 (range: 1-5), with nine patients (69.2%) having undergone autologous stem cell transplantation. Three patients (23.1%) were refractory to bortezomib, seven patients (53.8%) to lenalidomide, and eight patients (61.5%) to last treatment. At relapse, two (15.4%) had high LDH, eight (61.5%) impaired renal function, and three (23.1%) extramedullary disease. Treatment was dara-lenalidomide-dex in six (46.2%), and dara-pomalidomide-dex in seven (53.8%). Responses after four cycles included CR in 5 patients (38.5%), VGPR in five patients (38.5%), and PR in three patients (23.1%). After a median of four dara infusions (range: 3-10), the best responses included CR in seven patients (53.8%), nCR in two patients (15.4%), VGPR in two patients (15.4%), and PR in two patients (15.4%). Median time to VGPR was one month. At 10 months, the OS was 90%, and PFS 54.7%. Three patients progressed, one of whom died of ruptured hepatic plasmacytoma. The most frequent toxicity was haematological especially neutropenia (all grades: 92.3%, Grade ¾: 76.9%), infusion reaction (38.5%, all grade ½), neuropathy (38.5%, all grade ½), gastrointestinal (all grades: 38.5%, grade ¾: 7.7%), and sepsis (all grades: 30.8%; grade ¾: 23.1%). Neutropenia was effectively prevented with prophylactic G-CSF. Conclusions: In conclusion , a 3-weekly dara-IMiD-dex regimen is highly efficacious, inducing deep and rapid responses, hence cost-effective for less affluent countries. In view of prevalent grade 3/4 neutropenia despite less frequent dara, 3-weekly dara might be more suitable for Asian patients.

Systemic therapy for nonmetastatic castrate-resistant prostate cancer (M0 CRPC): A systematic review and network meta-analysis (NMA).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 113-113
Author(s):  
Ellen Cusano ◽  
Richard M. Lee-Ying ◽  
Devon J. Boyne ◽  
Darren Brenner ◽  
Marcus Vaska
Keyword(s):  
Fixed Effects ◽  
Meta Analysis ◽  
Cochrane Collaboration ◽  
Similar Efficacy ◽  
Risk Of Bias ◽  
Fixed Effects Model ◽  
Castrate Resistant Prostate Cancer ◽  
Grade 3 ◽  
Castrate Resistant ◽  
The Cochrane Collaboration

113 Background: The treatment landscape for M0 CRPC has changed following the demonstrated efficacy of new agents in recent randomized control trials (RCT). However, the comparative effectiveness of these novel agents is unknown. This NMA indirectly compared the efficacy and safety of available therapies for M0 CRPC. Methods: A literature search of MEDLINE (Ovid), EBM Reviews, HealthSTAR, PubMed, PubMed Central, CINAHL, and TRIP Database was performed. Studies were screened by two independent reviewers. Hazard ratios (HR) and confidence intervals were extracted for the primary outcome metastasis-free survival (MFS) and the secondary outcomes overall survival (OS) and grade 3 or higher adverse events (AE). Bone MFS was used as a surrogate for MFS when MFS was not reported. Risk of bias was assessed using the Cochrane Collaboration tool. A Bayesian NMA was performed using a fixed-effects model. Results: Four RCT were analyzed (n=5549). Each trial compared either apalutamide (APA), enzalutamide (ENZA), darolutamide (DARO), or denosumab (DENO) plus androgen deprivation therapy (ADT) to placebo plus ADT. Risk of bias was low. For MFS, APA and ENZA had similar efficacy (Table), and Surface Under the Cumulative Ranking Analysis demonstrated a 59% probability that APA was preferred for MFS, followed by ENZA (41%). There was a trend for improved OS for APA, DARO and ENZA, but no meaningful differences between these agents. APA, ENZA, and DARO had a similar risk of AEs and all had a greater risk of AEs compared to DENO. Conclusions: APA and ENZA appear to be the most efficacious treatments for MFS in M0 CRPC, though more data for OS is required. Compared to DARO, APA and ENZA’s demonstrated efficacy is not at the expense of added toxicity.[Table: see text]

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