scholarly journals A real-world comparative analysis of carfilzomib and other systemic multiple myeloma chemotherapies in a US community oncology setting

2019 ◽  
Vol 10 ◽  
pp. 204062071881669 ◽  
Author(s):  
Robert M. Rifkin ◽  
Rohan Medhekar ◽  
E. Susan Amirian ◽  
Kathleen M. Aguilar ◽  
Thomas Wilson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Real World Data ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Community Oncology ◽  
First Relapse ◽  
Line Of Therapy

Background: Most multiple myeloma (MM) patients ultimately progress, with remission duration decreasing after first relapse. Recently, novel agents have been approved for the treatment of relapsed MM. There is a paucity of real-world data on these treatments. We sought to compare time to next treatment (TTNT) in MM patients in their second line of therapy (LOT2), treated with common proteasome inhibitor (PI)-based triplets. Methods: Adult MM patients who received carfilzomib (K) between 1 November 2013 and 29 February 2016 at US Oncology Network (USON) clinics utilizing iKnowMed™ electronic health records (EHRs) were identified. Patients were included if they were ⩾18 years of age, not enrolled in clinical trials, had ⩾2 visits at a USON clinic and received LOT2 regimens consisting of: K+lenalidomide with steroid (KRd), bortezomib+lenalidomide with steroid (VRd), or bortezomib+cyclophosphamide with steroid (VCyd). TTNT was estimated from LOT2 initiation to LOT3 initiation using the Kaplan–Meier method, and hazard ratios (HRs) were estimated using Cox modeling. Results: A total of 718 patients received a K-containing regimen sometime during their MM treatment (LOT1 to LOT5). Of these, 156 patients received: KRd ( n = 112; 71.8%), VRd ( n =27; 17.3%), or VCyd ( n = 17; 10.9%). Baseline characteristics were similar between groups (mean age: 64.8 years; 58% male). Median TTNT was longest for KRd [25.3 months; 95% confidence interval (CI): 19.71–NR], versus VRd or VCyd (VRd median TTNT: 10.2 months, 95% CI: 4.24–12.71; VCyd: 6.5 months, 95% CI: 3.02–12.78; log-rank p < 0.0001). The adjusted HR for KRd was 0.19 (95% CI: 0.11–0.37), compared with VRd. Conclusions: Considering the real-world nature of these data, the median TTNT observed with KRd was relatively consistent, with progression-free survival (PFS) for KRd observed in the phase III ASPIRE trial (median PFS: ITT population = 26.3 months; LOT2 = 29.6 months). Patients who received KRd at first relapse had significantly longer TTNT, compared with those on VRd or VCyd, confirming the value of KRd as an important treatment option for relapsed MM.

scholarly journals Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real-world chart review study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shebli ATRASH ◽  
Philippe THOMPSON-LEDUC ◽  
Ming-Hui TAI ◽  
Shuchita KAILA ◽  
Kathleen GRAY ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Outcomes ◽  
Real World ◽  
Chart Review ◽  
Response Rate ◽  
Progression Free Survival ◽  
Treatment Patterns ◽  
Free Survival ◽  
Kaplan Meier ◽  
Line Of Therapy

Abstract Background Daratumumab, a CD38 monoclonal antibody, has demonstrated efficacy as monotherapy and combination therapy across several indications, both among newly-diagnosed and refractory patients with multiple myeloma (MM). However, there is limited evidence on treatment patterns and effectiveness of daratumumab in the real-world setting, particularly in first line (1 L). This study aimed to describe real-world treatment patterns and clinical outcomes among patients initiating daratumumab across different lines of therapy. Methods A retrospective chart review of adult patients with MM initiating daratumumab between November 2015 and March 2021 was conducted at two clinical sites in the United States. De-identified patient-level data were abstracted in an electronic case report form. Patient characteristics and treatment patterns were described. Clinical outcomes including overall response rate (ORR), progression-free survival, and time to next line of therapy were reported using descriptive statistics and stratified by line of therapy (1 L, second line [2 L] or third line or later [3 L+]). A sub-group analysis evaluated treatment patterns and ORR among patients re-treated with daratumumab. Results A total of 299 patients were included in the study (mean age: 68 years; 55% male). Among them, 26 were 1 L patients, 66 were 2 L patients, and 207 were 3 L+ patients; 110 patients (36.8%) received a stem cell transplant prior to daratumumab initiation. The mean duration of follow-up was 10 months among 1 L patients and 19 months among 2 L and 3 L+ patients. Patients who initiated daratumumab in 1 L had a 100% ORR, while those initiating in 2 L and 3 L+ had an ORR of 78.8 and 65.2%, respectively. Among re-treated patients, ORR was 66.7% during the first treatment segment, and 52.9% during the second treatment segment. Kaplan-Meier rates of progression-free survival at 12 months were 89.9, 75.2, and 53.1% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Kaplan-Meier rates of time to next line of therapy at 12 months were 94.1, 73.4, and 50.0% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Conclusions These findings suggest that daratumumab-based regimens are an effective treatment option across all lines of therapy, with highest response rate in 1 L.

scholarly journals Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World “POWERFUL” Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1509
Author(s):  
Evangelos Terpos ◽  
Panagiotis Repousis ◽  
Chrysavgi Lalayanni ◽  
Evdoxia Hatjiharissi ◽  
Theodora Assimakopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Low Dose ◽  
Safety Data ◽  
Progression Free Survival ◽  
Routine Care ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Line Of Therapy

The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan–Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade  ≥  3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.

scholarly journals Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US

2021 ◽  
Author(s):  
Faith Davies ◽  
Robert Rifkin ◽  
Caitlin Costello ◽  
Gareth Morgan ◽  
Saad Usmani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Comparative Effectiveness ◽  
Proteasome Inhibitors ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
The Us ◽  
Cox Proportional Hazard Models ◽  
Comparative Effectiveness Analysis ◽  
Line Of Therapy

AbstractMultiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum’s deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

The occurrence of grade 4 adverse events and survival outcomes in patients with nonsquamous non-small cell lung cancer receiving bevacizumab with chemotherapy in the phase III PointBreak and AVAiL studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19022-e19022
Author(s):  
Liza Cosca Villaruz ◽  
Mark A. Socinski ◽  
Jyoti D. Patel ◽  
Larry Leon ◽  
Sebastien Hazard ◽  
...  
Keyword(s):  
Cox Model ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
End Point ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

e19022 Background: Progression-free survival (PFS) is a key trial end point for clinical practice, as it relates to a change of treatment line. Grade 4 progression-free survival (G4PFS; defined as time from treatment start to the earlier of progressive disease [PD], onset of a G4 adverse event [AE], or death from any cause) is a composite end point incorporating a measure of tolerability to PFS. This post hoc analysis evaluates G4PFS and the effect of G4 AEs on PFS and overall survival (OS) in patients (pts) enrolled in PointBreak (PB) and AVAiL. Methods: Pts in PB were randomized to bevacizumab (BEV) 15 mg/kg q3w with carboplatin and paclitaxel (CP) or pemetrexed (CPem) for ≤4 cycles. Eligible pts received either BEV or BEV + Pem q3w until PD or unacceptable toxicity. Pts in AVAiL received cisplatin and gemcitabine for ≤6 cycles and either placebo or BEV (7.5 or 15 mg/kg) q3w until PD. AEs were graded via NCI-CTCAE v3.0. Kaplan-Meier and Cox model methods were used to estimate medians and hazard ratios (HRs) for PFS, G4PFS, and OS. PFS and OS were also compared in each arm for pts with occurrence of a G4 AE before week 12 of treatment vs those without. Results: Of those receiving BEV, ~30% of AVAiL pts and 38% of PB pts had a G4 AE. Uncomplicated neutropenia was the most common G4 AE in the CP + BEV arm of PB (26%) and in the BEV arms of AVAiL (11%). PFS, G4PFS, and outcomes by G4 AE occurrence are shown (Table). Conclusions: In both the PB and AVAiL trials, median G4PFS was numerically shorter than median PFS. G4 AE occurrence, however, did not affect subsequent PFS or OS in either trial. Clinical trial information: NCT00762034 and NCT00806923. [Table: see text]

Comparison of lenalidomide plus dexamethasone therapy used at first relapse versus later salvage therapy in relapsed or refractory multiple myeloma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8594-8594
Author(s):  
E. A. Stadtmauer ◽  
D. M. Weber ◽  
R. Nieszvizky ◽  
A. Belch ◽  
H. M. Prince ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Response Rate ◽  
Early Stage ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Duration Of Treatment ◽  
Refractory Multiple Myeloma ◽  
Prior Therapy ◽  
First Relapse

8594 Background: The benefit of initiating lenalidomide plus dexamethasone at first relapsed was evaluated in this subset analysis from phase III studies in patients with relapsed or refractory multiple myeloma (MM). Methods: Patients from the randomized, multicenter clinical trials MM-009 and MM-010 who had received at least 1 prior treatment and were not resistant to dexamethasone were treated with lenalidomide (25 mg daily for 21 days of every 28 day cycle) plus dexamethasone (40 mg on days 1–4, 9–12, and 17–20 every 28 days for 4 months, then 40 mg on days 1–4 every cycle thereafter until disease progression or intolerance), or dexamethasone (same dose and schedule) plus placebo. Baseline characteristics such as age, sex, ECOG score, and baseline β2-microglobulin levels between the 2 patient groups were similar, however, median time from diagnosis and prior therapy were statistically different. Results: Multivariate analysis showed that more prior therapies is associated with shorter time-to-progression (TTP). Patients who received 1 prior therapy demonstrated a significant improvement in outcomes such as TTP, progression-free survival (PFS), overall response rate (ORR), complete response/very good partial response rate (CR/VGPR), median duration of treatment and overall survival (OS) after first relapse compared with those who received ≥ 2 prior therapies ( Table ). Toxicity, rate of dose reduction, or treatment discontinuation in the cohort with 1 prior therapy did not increase, despite longer treatment. Conclusions: When used at first relapse compared with salvage therapy, lenalidomide plus dexamethasone treatment resulted in significantly prolonged TTP, PFS, and OS, and an improved quality of response. Lenalidomide plus dexamethasone should be considered at an early stage of therapy for patients with MM. [Table: see text] [Table: see text]

Prospective, multicenter, noninterventional and registry clinical study of apatinib in patients with advanced gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 137-137 ◽  
Author(s):  
Chunmei Bai ◽  
Diansheng Zhong ◽  
Ruixing Zhang ◽  
Xiubao Ren ◽  
Likun Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Efficacy Evaluation ◽  
Real World Data ◽  
Skin Reactions

137 Background: The aim of this study was to observe the safety of apatinib in the real world with wider inclusion criteria. The efficacy of apatinib was evaluated including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Methods: This trial enrolled patients from 32 centers in china with advanced gastric adenocarcinoma who had progressed after undergoing at least two lines of systemic chemotherapy, or patients who were considered to benefit from the treatment. We recommended starting from oral administration of 500mg qd, 28 days for a cycle. Dose could be appropriately adjusted according to the patients’ physical condition. Results: Between March 2015 and September 2017, 326 patients were enrolled. The average age was 62 years old, and the ratio of male to female was about 2:1. Patients received perioperative, first-line, second-line, and third-line or more treatment were 1,39,69 and 217 people respectively. There were 192 patients received efficacy evaluation, 9 patients achieved partial response(PR), 125 had disease stability(SD). The ORR and DCR were 4.6% and 69.8% respectively. The median PFS and median OS were 3.7 months and 7.3 months respectively. In the 326 patients, there were 153 patients with initial dose of 500 mg, 3 and 55 patients achieved PR and SD, respectively. The ORR and DCR were 3.3% and 63.7%, respectively. The median PFS and median OS were 3.5 months and 8.4 months, respectively. There were 237 patients in all 326 patients received safety analysis. Common adverse events were hypertension (57%), hand-foot skin reactions (26.6%), fatigue (29.5%), proteinuria (19.0%), bleeding (10.1%) and diarrhea (8.0%). The grade 3 to 4 adverse events were hypertension (6.3%), hand-foot skin reactions (3.8%), proteinuria(3.0%) and bleeding (2.1%). Conclusions: This real-world data in which more patients were given apatinib 500mg or less qd showed similar efficacy to Phase III clinical trial (850mg qd).The incidence of adverse events was consistent with that of Phase III clinical data,there was no new adverse events had been seen. Clinical trial information: NCT02668380.

Isatuximab, carfilzomib and dexamethasone (Isa-Kd) for the management of relapsed multiple myeloma

2021 ◽  
Author(s):  
Rahul Banerjee ◽  
Mimi Lo ◽  
Thomas G Martin
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Trial Experience ◽  
The Usa ◽  
Clinical Trial Experience ◽  
Line Of Therapy

The treatment of relapsed multiple myeloma remains challenging. Based on interim data from the randomized Phase III IKEMA study demonstrating a progression-free survival benefit with a combination of isatuximab (Isa, a CD38-targeted monoclonal antibody) and carfilzomib/dexamethasone (Kd) versus Kd alone, Isa-Kd recently received regulatory approval in the USA and Europe for patients with multiple myeloma who have received at least one prior line of therapy (in the USA, up to three prior lines). In this review we discuss the rationale and clinical trial experience to date with Isa-Kd. Although final IKEMA results are pending, Isa-Kd has emerged as an effective and tolerable therapy for patients with relapsed multiple myeloma. Given the growing number of antibody-containing triplet regimens in this setting, potential niches and limitations for Isa-Kd are also discussed.

Relation Between Cereblon Expression and Survival in Patients with Newly Diagnosed Multiple Myeloma Treated with Thalidomide

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3973-3973
Author(s):  
Annemiek Broyl ◽  
Rowan Kuiper ◽  
Mark van Duin ◽  
Bronno van der Holt ◽  
Laila el Jarari ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Hazard Ratios

Abstract Abstract 3973 Introduction: Cereblon (CRBN) expression has been described to be essential for the activity of Thalidomide and Lenalidomide. This suggests that presence and possibly increased level of CRBN expression would be associated with better outcome in Thalidomide/Lenalidomide treated patients. The aim of this study was to evaluate CRBN expression in relation to outcome in patients receiving Thalidomide maintenance. Patients and methods: The HOVON-65/GMMG-HD4 trial is a multi-center, phase III trial, comparing Bortezomib in induction and post-intensification vs. conventional chemotherapy and daily Thalidomide 50 mg for 2 years post-intensification in newly diagnosed MM patients. This trial demonstrated that Bortezomib during induction and maintenance improved CR and achieved superior PFS and OS (Sonneveld et al., JCO, July 16, 2012). Gene expression profiling was performed at the start of the trial by Affymetrix U133 Plus 2.0 GeneChip, and was available for 96 patients which started Thalidomide maintenance. CRBN expression levels were based on a combined value of probe sets 218142_s_at and 222533_at. CRBN expression was validated using real-time PCR. All survival analyses were performed in SPSS, with survival time taken from the start of maintenance. Results: In patients receiving Thalidomide maintenance, increased CRBN expression was significantly associated with longer progression free survival (p=0.005, hazard ratio = 0.7) and longer overall survival (p=0.04, hazard ratio= 0.7). Using Kaplan-Meier analysis for visualization and using the median expression to define high and low expression, a significant separation was found for PFS (Log rank p=0.009) but not for OS (Log rank p=0.13). No association was observed between CRBN expression and PFS/OS after Bortezomib maintenance (PFS, p=0.4, hazard ratio=1.1; OS, p=0.7, hazard ratio=1.1). Multivariate Cox regression analysis was performed using the covariates ISS, CRBN and high-risk cytogenetics, defined as having del(17p) and/or 1q gain and/or t(4;14). Higher CRBN levels remained significantly related to longer PFS (hazard ratio 0.7, p=0.03), but not OS (hazard ratio of 0.8, p=0.3). High-risk cytogenetics and ISS were both significant in both PFS and OS multivariate models, with hazard ratios of 2.8 and 3.6, for high-risk cytogenetics and 2.5 and 5.5, for ISS stage 3, respectively (p=0.0004, p=0.003, high-risk cytogenetics and p=0.01 and p=0.005, ISS stage 3, respectively). Conclusion: These data suggest use of CRBN as a biomarker for thalidomide outcome, but further analysis in other Thalidomide trials is required to validate this finding. Disclosures: Lokhorst: Genmab: Consultancy. Sonneveld:Onyx: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; celgene: Honoraria, Research Funding.

scholarly journals 53 Predictors of response to immune checkpoint inhibitor therapy in metastatic solid tumors: real world evidence

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A57-A58
Author(s):  
Aasems Jacob ◽  
Jianrong Wu ◽  
Jill Kolesar ◽  
Eric Durbin ◽  
Aju Mathew ◽  
...  
Keyword(s):  
Real World ◽  
Immune Checkpoint Inhibitor ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Real World Data ◽  
Free Survival ◽  
Mutational Burden ◽  
Kaplan Meier ◽  
Tumor Mutational Burden ◽  
Study Population

BackgroundImmune checkpoint inhibitor (ICI) therapy is increasingly being used in oncology and novel predictive biomarker for efficacy and side effects are an unmet need.1 2 The study aims to do a comprehensive analysis of factors affecting outcome from ICI therapy with real-world data and identify potential predictive biomarkers in diverse populations.MethodsWe performed a retrospective analysis of patients with metastatic solid tumors who received ICI and underwent molecular profiling with FoundationOne® CDx panel between 2016 and 2020 at Markey Cancer Center, Lexington KY. Progression-free survival (PFS), radiological response, and autoimmune side effects were analyzed and compared with various molecular biomarkers (figure 1). Logistic regression, Fisher’s exact test, Kaplan-Meier method, log-rank test, and Cox regression were used to analyze clinical features and efficacy outcomes.Abstract 53 Figure 1Mutational analysis of patients receiving immunotherapy grouped based on radiologic response, in the order of mutational load and frequency of mutationsAbstract 53 Figure 2Kaplan-Meier graphs depicting progression free survival in patients based on tumor samples showing (a) High TMB and low/intermediate TMB; (b) PDL1 expression; (c) Presence of IRAEs; (d) Presence of PIK3 mutation; (e) Presence of FGFR mutation; (f) Presence of BRAF mutationAbstract 53 Table 1Baseline characteristics of the study populationAbstract 53 Table 2Treatment and biomarker characteristics of study populationAbstract 53 Table 3ORR based on various factors with odds ratio calculated using logistic regression modelAbstract 53 Table 4Identified PIK3 mutations in tumor samples, with their chromosomal position and protein changesResults69 patients were included in the study (tables 1 and 2). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR=2.51. 95%CI 1.23, 5.14; table 3 and figure 2). This was independent of tumor mutational burden (TMB) status or PDL1 expression status (HR 3.24, p=0.016). PIK3 mutants had a higher overall response rate (ORR) than the wild type (69.6% vs. 43.5%, OR 0.34; p=0.045; tables 3 and 4). PIK3 mutants had a higher risk of developing immune-related adverse events (IRAEs) (73.9% vs. 37%, p=0.004). PIK3 mutation did not associate with TMB, PDL1 expression or microsatellite stability status. Median PFS was higher in the high TMB cohort compared to the low-intermediate group and reached statistical significance (median not reached vs. 26 weeks; HR=0.37. 95%CI 0.13, 1.05). PDL1 expression had no significant effect on the radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended towards statistical significance (median 18 vs. 40 weeks. HR=1.43. 95%CI 0.93, 4.46). BRAF mutation conferred shorter PFS (median 17 vs. 39 weeks. HR=0.35. 95%CI 0.14, 0.91) (figure 2).ConclusionsHigh tumor mutational burden and PIK3 mutation conferred better progression-free survival with immunotherapy across cancer types. The improvement in PFS in PIK3 mutated patients was independent of PDL1 status or TMB. The results should prompt further evaluation of these potential biomarkers and more widespread real-world data publications to help determine biomarkers that could benefit specific populations.Ethics ApprovalThe study was approved by University of Kentucky Institutional Review Board, approval number 49450ReferencesTopalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–2454.Spencer KR, Wang J, Silk AW, Ganesan S, Kaufman HL, Mehnert JM. Biomarkers for Immunotherapy: Current Developments and Challenges. Am Soc Clin Oncol Educ Book. 2016; 35:e493–503.

Real-world duration of maintenance therapy in 2nd-line and later ovarian cancer (OC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17103-e17103
Author(s):  
David Garofalo ◽  
Ebru Aydin ◽  
Monica Labrador ◽  
Jennifer Webster ◽  
Joseph Donaldson ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Real World ◽  
Data Exchange ◽  
Maintenance Treatment ◽  
Observation Time ◽  
Time Interval ◽  
Real World Data ◽  
Community Oncology ◽  
Significant Difference ◽  
Line Of Therapy

e17103 Background: Recurrent OC patients may benefit from maintenance therapy, with the goal of inducing a lasting remission or extending the time interval before progression without any deleterious impact on quality of life1. This analysis, based on real world data sourced from US community oncology practices, was designed to compare the time to next treatment of available maintenance treatment options in recurrent OC. Methods: This analysis utilized the Integra Data Exchange (DTX) database, a deidentified data source from community oncology practice systems (EMR, claims). This retrospective study included 3,629 OC patients with at least two visits between 7/16/16 and 4/16/18. 1,767 patients started at least one 2nd line or later line of therapy and 577 of these patients had at least one line of maintenance treatment. Maintenance options were monotherapy PARP inhibitors, Bevacizumab, or non-platinum-chemotherapy. Patients who did not receive maintenance were categorized as observation. Time to next treatment (start of maintenance to start of next line of therapy) was compared through ANOVA and paired T-test analyses. Results: A statistically significant difference was seen in time to next treatment between PARPi (n = 151) and bevacizumab maintenance (n = 212) (p = < 0.0125) and between PARPi and cytotoxic maintenance (n = 163) (p = < 0.0001). Bevacizumab and PARPi maintenance had significantly longer duration when compared to observation (n = 1,626) (p = < 0.0001). Cytotoxic maintenance duration was not significantly different than observation (p = 0.93). Conclusions: Our real world analysis found that there was a statistically significant increase in time to subsequent lines of therapy when certain maintenance treatment (PARPi, Bevacizumab) is utilized following 2nd line and later treatment in OC. Further, between available maintenance options, PARPi had the longest time to next treatment when compared to other maintenance options.[Table: see text]

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