Magnitude of progression-free survival (PFS) improvement and treatment (Tx) duration in metastatic colorectal cancer (mCRC) for bevacizumab (BV) in combination with oxaliplatin-containing regimens: An analysis of two phase III studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
B. J. Giantonio ◽  
N. J. Meropol ◽  
P. J. Catalano ◽  
V. Ng ◽  
R. Oliver ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Two Phase ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Phase Iii Studies

4073 Background: In trials of BV with FOLFOX (fluorouracil, leucovorin, oxaliplatin) for mCRC, variability in the magnitude of PFS improvement has been reported [HR=0.61 in E3200 vs HR= 0.83 (FOLFOX or CAPOX (capecitabine and oxaliplatin)) in NO16966]. We propose that differences in rates of treatment discontinuation (D/C) for adverse events (AE) between these studies may have resulted in differences in the observed benefits associated with BV. We explored Tx duration (proportion of patients on Tx) and Tx D/C data at median PFS for the BV containing arms of each study. Methods: ECOG study E3200 randomized previously treated patients with mCRC to FOLFOX ± BV (10 mg/kg). NO16966 employed a 2x2 design that randomized previously untreated patients with mCRC to CAPOX vs FOLFOX and to BV (5 mg/kg) or placebo. In both trials, study Tx was defined as any component of the prescribed regimen. PFS was estimated from Kaplan-Meier curves, and hazard ratios (HR) for PFS were estimated by Cox regression. Results: Median PFS for the BV containing arm of the study: 30 weeks for E3200; 42 weeks for NO16966 Conclusion: These data suggest possible differences between the two studies in Tx duration and Tx D/C patterns with a greater proportion of patients on NO16966 discontinuing Tx for any AE. Duration of study Tx might have affected both the incidence of AEs and the magnitude of PFS benefit observed for the addition of bevacizumab to oxaliplatin-based chemotherapy in these studies. Attention to Tx duration and Non-PD Tx D/C in future clinical trials will be important when considering PFS as a primary efficacy endpoint. [Table: see text] No significant financial relationships to disclose.

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]

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 Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11516-11516
Author(s):  
Chang Gon Kim ◽  
Jin-Hee Ahn ◽  
Jeong Eun Kim ◽  
Jee Hung Kim ◽  
Min Kyung Jeon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic BRCA1/2 (sBRCA) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10512-10512
Author(s):  
Felipe Batalini ◽  
Russell Madison ◽  
Dean C. Pavlick ◽  
Ethan Sokol ◽  
Tamara Snow ◽  
...  
Keyword(s):  
Cox Regression ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Free Survival ◽  
Pathogenic Variants ◽  
Kaplan Meier ◽  
Pathway Gene ◽  
Comprehensive Genomic Profiling

10512 Background: PARPi are approved for treatment of pts w/ HER2-negative mBC and germline BRCA1/2 (g BRCA) pathogenic or likely pathogenic variants (muts); however, clinical benefit has also been demonstrated in mBC pts w/ sBRCA or other HR-pathway gene muts. Using a RW Clinico-Genomic Database (CGDB), we assessed outcomes for pts w/ gBRCA muts compared to pts w/ either s BRCA or other HR-pathway muts treated w/ PARPi. Methods: 6,329 mBC pts from ̃280 US cancer clinics were included in the Flatiron Health (FH) -Foundation Medicine (FM) CGDB, which includes comprehensive genomic profiling (CGP) linked to de-identified, electronic health record (EHR)-derived clinical data. Eligible pts had mBC, received care in the FH network from 1/1/2011-9/1/2020, and had tissue CGP by FM. Pts classified as gBRCA: positive germline result in EHR and BRCA mut predicted germline per FM’s somatic, germline, zygosity algorithm (SGZ) (Sun et al PMID 29415044). Non-g BRCA: negative germline results in EHR and a somatic BRCA (s BRCA) mut per SGZ or BRCA wild-type w/ another HR mut per CGP result. Pts w/o a documented gBRCA result in EHR, unknown FM BRCA SGZ result, or conflicting results were excluded. RW overall survival (rwOS) and RW progression-free survival (rwPFS) from start of PARPi for pts w/ gBRCA and non- gBRCA mBC were compared using Kaplan-Meier analysis and Cox regression adjusted for mBC line number, prior platinum, age at PARPi initiation, race, and receptor status. Results: Among pts who received PARPi in the mBC setting, 44 had gBRCA and 18 had non -gBRCA: 9 s BRCA (5 BRCA1, 4 BRCA2), 4 PALB2, 2 ATM, and 1 each of ATM+CDK12, BARD1+FANCF+RAD54L, and CHEK2. Of HR muts 76% were confirmed biallelic: 33/44 gBRCA (11 unknown), 8/9 sBRCA, 3/4 PALB2, and 3/5 other (1 unknown). Neither median rwPFS nor rwOS from start of PARPi were significantly different between the non-g BRCA and g BRCA cohorts (rwPFS: 7.0 [4.6-11.3] vs 5.5 [4.3-7.2] months (mos), aHR: 1.19 [0.57 – 2.43]; rwOS: 15.0 [7.95-16.3] vs 11.5 [9.46-NA] mos, aHR: 0.85 [0.36-1.98]). For 9 pts w/ sBRCA mut, median rwPFS was 7.1 mos (range 1.4-12.4) and all pts had progressed by data cut off. Conclusions: Despite small pt numbers and limitations from RW data, our results suggest that pts w/ biallelic non-g BRCA mBC may derive similar benefit from PARPi when tumor CGP detects a s BRCA mut or germline or somatic mut in other HR-pathway genes. These findings are consistent w/ the results from TBCRC-048 (Tung et al PMID 33119476) and support further randomized trials exploring the efficacy of PARPi in this population.[Table: see text]

Efficacy of Daratumumab Based Regimens Compared to Standard of Care for Transplant Ineligible Newly Diagnosed Multiple Myeloma in Phase III Clinical Trials: A Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-33
Author(s):  
Zahoor Ahmed ◽  
Karun Neupane ◽  
Rabia Ashraf ◽  
Amna Khan ◽  
Moazzam Shahzad ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Standard Care ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Control Group ◽  
Two Phase ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Phase Iii Clinical Trials

Introduction: Daratumumab (Dara) is a human anti-CD38 monoclonal antibody approved for multiple myeloma (MM) treatment. Dara has a promising efficacy and a favorable safety profile in newly diagnosed MM (NDMM) patients. This study is focused on the efficacy and safety of Dara when added to the standard care regimen in transplant ineligible NDMM in phase III clinical trials. Methods: We performed a comprehensive database search on four major databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov). Our search strategy included MeSH (Medical Subject Headings) terms and key words for multiple myeloma and Dara including trade names and generic names from date of inception to May 2020. Initial search revealed 587 articles. After excluding review articles, duplicates, and non-relevant articles, two phase III clinical trials were included which reported overall response rate (ORR), and progression free survival (PFS) of transplant ineligible NDMM patients with Dara addition to standard care regimen. Odds ratios (OR) of ORR were computed and hazard ratios (HR) of PFS (along with 95% confidence intervals; CI) were extracted to compute a pooled HR using a fixed effect model in RevMan v.5.4. Results: A total of 1453 transplant ineligible NDMM patients were enrolled and evaluated in two phase III randomized clinical trials. Seven hundred and eighteen patients were in Dara group and 735 patients were in control group. Bahlis et al. (2019) studied Dara + lenolidamide (R) and dexamethasone (d) vs Rd in NDMM pts (n=737) in MAIA phase III trial. Similarly, Mateos et al. (2018) reported the role of Dara + bortezomib (V) + melphalan (M), and prednisone (P) vs VMP in NDMM pts (n=706) in a phase III trial (Alcyone). A pooled analysis of these phase III trials showed ORR (OR: 3.26, 95% CI 2.36-4.49; p &lt; 0.00001, I2 = 0%), and progression free survival (PFS) (HR: 0.53, 95% CI 0.43-0.65; p &lt; 0.00001, I2 = 0%). Achievement of minimal residual disease (MRD) negative status was significant in Dara based regimen as compared to control group (OR: 4.49, 95% CI 3.31-6.37; p &lt; 0.00001, I2 = 0%). Dara addition to standard care regimen (Rd and VMP) decreased the risk of progression/death to 42% (HR: 0.58, 95% CI 0.48-0.70; p &lt; 0.00001, I2 = 0%). The addition of Dara increased the risk of neutropenia (OR: 1.41, 95% CI 1.07-1.85; p &lt; 0.02, I2 = 44%), and pneumonia (OR: 2.25, 95% CI 1.54-3.29; p &lt; 0.0001, I2 = 37%) vs control group. However, decreased risk of anemia (OR: 0.64, 95% CI 0.49-0.85: p &lt; 0.002, I2=30%) was observed in Dara group vs control group (Figure 1). Conclusion: Addition of Dara to the standard care regimen for transplant ineligible NDMM achieved the surrogate end points with improved efficacy and MRD negative status with manageable toxicity. However, data from more randomized controlled trials is needed. Table Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Assessment of Targeted Systemic Exposure Based on Ex-Vivo Concentrations of Bendamustine and Chlorambucil and Related Clinical Outcomes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4211-4211
Author(s):  
Mona Darwish ◽  
Peter Brown ◽  
Debra M Bensen-Kennedy ◽  
Lauren Young
Keyword(s):  
Ex Vivo ◽  
Peak Plasma ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Previously Treated Patients ◽  
Previously Treated

Abstract The alkylating agent bendamustine (100 mg/m2 iv) was recently shown to be superior to chlorambucil (0.8 mg/kg po) in the treatment of patients with chronic lymphocytic leukemia, in respect to both overall response rate and progression-free survival (Knauf et al 2007). In order to better understand the greater activity exhibited by bendamustine, the ex-vivo potencies of these two drugs against primary CLL cells were compared with the peak plasma concentrations obtained in patients. Published studies indicate that ex-vivo bendamustine treatment results in a mean LD50 (dose causing 50% cell death) of 7.4 and 4.3 μg/ml in CLL cells from chemo-naive and previously-treated patients respectively (Schwanen et al 2002). This is comparable to the Cmax attained in patients: a 120 mg/m2 dose of bendamustine infused over 60 min resulted in a mean Cmax of 5.6 μg/ml in a study of lymphoma patients. In contrast, the corresponding LD50 values for chlorambucil were reported to be 12.3 and 26.2 μg/ml for chemo-naive and previously-treated CLL patients (Silber et al 1994). These concentrations are considerably higher than the plasma concentrations attained with oral administration of chlorambucil: an oral dose of 60 mg (~0.8 mg/kg) resulted in a mean Cmax of 2.2 μg/ml of parent compound and 1.1 μg/ml of the active phenylacetic acid metabolite. A higher dose of 70 mg did not result in higher plasma exposure (Hartvig et al 1988). The ability to achieve adequate therapeutic concentrations of bendamustine in CLL patients may explain, in part, the greater activity observed with this novel chemotherapy as compared to chlorambucil.

Impact of bevacizumab dose reduction on clinical outcomes for patients treated on the Eastern Cooperative Oncology Group’s Study E3200

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3538-3538 ◽  
Author(s):  
B. J. Giantonio ◽  
P. J. Catalano ◽  
P. J. O’Dwyer ◽  
N. J. Meropol ◽  
A. B. Benson
Keyword(s):  
Dose Reduction ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hazard Ratios ◽  
Previously Treated ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Colorectal Cancer Patients ◽  
Dose Modifications ◽  
Dose Reductions

3538 Background: E3200 demonstrated improved survival (OS) for previously treated metastatic colorectal cancer patients who received second-line therapy with bevacizumab (10 mg/kg) in combination with FOLFOX4. Dose reductions of bevacizumab to 5 mg/kg were allowed for: hypertension, bleeding and thrombosis of ≤ grade 2; proteinuria of > 2 grams/24 that resolved to <0.5 grams/24hrs; liver function abnormalities ≥ grade 3 that resolved to ≤ grade 1. Methods: Data on dose modifications of bevacizumab were obtained from a post-study survey of participating institutions for all participants. Median OS and progression-free survival (PFS) were determined based upon a dose reduction any time during treatment. Hazard ratios (HR) for OS and PFS were stratified by number of cycles (1–5, 6–10, 11+) to adjust for the time-varying nature of dose reductions. Results: Surveys were received on 84% of E3200 patients treated with bevacizumab. Dose reductions of bevacizumab were performed in 134 of 240 (55.8%) patients treated with FOLFOX + bevacizumab (Arm A) and 77 of 205 (37.6%) patients treated with bevacizumab alone (Arm C). The average number of cycles of bevacizumab administered at a dose reduction for Arm A is 42% and for Arm C is 52%. Conclusions: OS and PFS on E3200 were not compromised for patients who underwent dose reductions of bevacizumab. [Table: see text] [Table: see text]

Is conversion to resection possible with hepatic arterial infusion (HAI) and systemic (SYS) even in previously treated patients (pts) with unresectable colorectal liver metastases (UnCLM)?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3577-3577 ◽  
Author(s):  
Nancy E. Kemeny ◽  
Yuman Fong ◽  
Philip Paty ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
...  
Keyword(s):  
Regression Model ◽  
Cox Regression ◽  
Hepatic Arterial Infusion ◽  
Progression Free Survival ◽  
Multivariate Logistic Regression Model ◽  
Kaplan Meier ◽  
Pump Placement ◽  
Previously Treated ◽  
Portal Veins ◽  
Hepatic Portal

3577 Background: Previously, we showed thatHAI with FUDR + dexamethasone (Dex) plus SYS produced a 47 % resectability rate in a retrospective study of 49 pts with UnCLM. Methods: Prospectively evaluated UnCLM pts in a new protocol were combined with the above protocol (n=105 pts) and all were treated with HAI FUDR/Dex + Sys. Unresectability was defined as diffuse bilateral metastases, involvement of all hepatic/portal veins, and/or inability to preserve remaining liver with adequate perfusion. Factors associated with conversion were identified using a multivariate logistic regression model. Overall survival (OS) and progression free survival (PFS) were calculated from pump placement by the Kaplan-Meier method. Resectability was a time-dependent covariate in a Cox regression model. Results: 61 of the 105 pts had prior SYS (56 %with prior Oxali) and 45 (74%) were progressing at the time of pump placement. In previously treated pts, 44% underwent resection, with a median OS of 45 mos. Of 44 chemo-naïve pts, 57% underwent hepatectomy, with a median OS of 68 mos. The following were significantly associated with resection conversion: lesion number [p=0.02], baseline CEA [p=0.04], females [p=0.03] and clinical risk score (CRS) [p=0.05]. In multivariate analysis, gender and CRS remained predictive of resectability. Surgery greatly reduced the hazard of death by 67% [HR: 0.33, 95%CI: 0.17-0.61, p=0.0004], after adjusting for several risk factors (Table). Median PFS was 12 mos for all pts. Conclusions: Even in previously treated pts,HAI + SYS is an approach to convert UnCLM to resection. Gender and CRS are associated with conversion to resectability. [Table: see text]

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