Modified IPCW model: A method for adjusting for bias in the estimation of overall survival due to the use of second and third line therapies in locally advanced or metastatic pancreatic cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15787-e15787
Author(s):  
N. E. Iznaga Escobar ◽  
Patricia Lorenzo Luaces ◽  
Lizet Sanchez Valdes ◽  
Carmen Valenzuela Silva ◽  
Tania Crombet Ramos ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Cox Regression ◽  
Locally Advanced ◽  
Secondary Analysis ◽  
Metastatic Pancreatic Cancer ◽  
Fixed Dose ◽  
Line Treatment ◽  
Newly Diagnosed

e15787 Background: Nimotuzumab, a unique and affinity differentiated anti-EGFR antibody had been used in combination with gemcitabine on the treatment of pancreatic cancer patients. The aim of the study was to evaluate overall survival. Methods: Patients with newly diagnosed, locally advanced or metastatic pancreatic cancer, KPS ≥ 70 %, 18-72 years old, with adequate renal and liver function were included. Pts received gemcitabine 1000 mg/m2and nimotuzumab or placebo fixed dose of 400 mg once a wk, for 3 wks, followed by a 1-wk rest (d1, 8, 15, q28) until disease progression or unacceptable toxicity. The primary endpoint was OS and secondary PFS, ORR, CBR, safety and QoL. For OS determination, a KM log-rank test was used and a modified IPCW with a cox regression as a secondary analysis. On this evaluation using a modified IPCW model, 41.7% of pts from treatment arm and 42.7% from control arm who received 2nd and 3rd line treatment were censored after progression, while pts that did not receive 2nd and 3rd line treatment were weighted to compensate for the bias created by censoring switchers to 2nd and 3rd line treatment. Results: 192 pancreatic cancer pts were recruited. Ninety-six pts (62 male and 34 female) with a median age of 67 years, range (31, 83) were randomized to treatment arm and 96 pts (57 male and 39 female) with a median age of 64 years, range (41, 82) were randomized to control arm. In the primary analysis, median OS [95% CI] in the treatment arm was 8.57 mo [5.93, 10.90] vs 6.03 mo [4.97, 7.60] in the control arm. The HR [95% CI], 0.83 [0.62, 1.12] and p = 0.23 and when a modified IPCW model as a secondary analysis was used to remove the effect of 2nd and 3rd line therapies, the median OS was statistically significant with a HR [95% CI], 0.81 [0.67, 0.98] and a p = 0.030. The median PFS [95% CI] was 4.43 mo [3.67, 6.00] in the treatment arm vs 3.47 mo [2.60, 4.03] in the control arm with a HR [95% CI] 0.68 [0.51, 0.92] and p = 0.012. Conclusions: A modified IPCW model had proven that addition of nimotuzumab to gemcitabine increases median overall survival of newly diagnosed chemotherapy-naïve locally advanced or metastatic pancreatic cancer patients. Clinical trial information: NCT00561990.

A phase II study of lapatinib and capecitabine in first-line treatment of metastatic pancreatic cancer (ICORG 08- 39).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 315-315 ◽  
Author(s):  
R. S. McDermott ◽  
P. Calvert ◽  
M. Parker ◽  
G. Webb ◽  
B. Moulton ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Survival Duration ◽  
Synergistic Activity ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]

scholarly journals Impact of New Chemotherapy Regimens on the Treatment Landscape and Survival of Locally Advanced and Metastatic Pancreatic Cancer Patients

2020 ◽  
Vol 9 (3) ◽  
pp. 648 ◽  
Author(s):  
Markus Kieler ◽  
Matthias Unseld ◽  
Daniela Bianconi ◽  
Martin Schindl ◽  
Gabriela V. Kornek ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Survival Rates ◽  
Cox Proportional Hazards Model ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
First Line

Background: New chemotherapy regimens for the treatment of metastatic pancreatic cancer have changed the therapy paradigm. We aimed to assess their impact on the treatment landscape and clinical outcome at our academic institution. Methods: In this single institutional posthoc registry analysis, we assessed characteristics and survival rates from all patients with locally advanced and metastatic pancreatic cancer who started a systemic treatment between 01/2011 and 12/2017. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model. Results: A total of 301 patients started a systemic treatment in the observation period. In the first line treatment, we observed a shift from the four different main regimens (gemcitabine/nab-paclitaxel, modified FOLFIRINOX, gemcitabine/oxaliplatin +/− erlotinib or gemcitabine alone) to gemcitabine/nab-paclitaxel and modified FOLFIRINOX that add up to more than 80% of administered first line treatments in each of the time cohorts (2011–2013 vs. 2014–2017). The rate for first line modified FOLFIRINOX treatment was balanced between the two groups (19% and 15%). Median overall survival differed significantly between the two time cohorts (8.89 versus 11.9 months, p = 0.035). Survival rates for different first to second line treatment sequences (modified FOLFIRINOX to gemcitabine/nab-paclitaxel, gemcitabine/nab-paclitaxel to fluoropyrimidines plus nanoliposomal irinotecan, or gemcitabine/nab-paclitaxel to fluoropyrimidines plus oxaliplatin) were not significantly different and median overall survival ranged from 14.27 to 15.64 months. Conclusion: Our study provides real-world evidence for the effectiveness of the new chemotherapy regimens and underscores the importance of the choice of the front-line regimen when considering different sequencing strategies.

scholarly journals Immunological predictors of overall survival in treatment naïve metastatic pancreatic cancer patients

2015 ◽  
Vol 3 (S2) ◽  
Author(s):  
Matthew R Farren ◽  
Thomas Mace ◽  
Susan Geyer ◽  
Sameh Mikhail ◽  
Christina Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Metastatic Pancreatic Cancer ◽  
Treatment Naïve

205 SPARC gene variants predict survival of locally advanced and metastatic pancreatic cancer patients treated with chemotherapy

2015 ◽  
Vol 51 ◽  
pp. S28
Author(s):  
C. Arqueros ◽  
D. Paez ◽  
J. Salazar ◽  
E. Del Rio ◽  
M.J. Arranz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Metastatic Pancreatic Cancer ◽  
Gene Variants

Overall survival with preoperative biliary drainage in patients with resectable pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 314-314
Author(s):  
Tobin Joel Crill Strom ◽  
Sarah E. Hoffe ◽  
Shivakumar Vignesh ◽  
Jason Klapman ◽  
Cynthia L. Harris ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Size ◽  
Biliary Drainage ◽  
Cox Regression ◽  
Neoadjuvant Treatment ◽  
Preoperative Biliary Drainage ◽  
Resectable Pancreatic Cancer ◽  
Pathologic Features

314 Background: Resectable pancreatic cancer patients often present with obstructive jaundice necessitating the placement of biliary stents or percutaneouse drainage catheters. We sought to evaluate whether preoperative biliary drainage affects recurrence and survival. Methods: An IRB-approved study was conducted on our institutional tumor registry to identify pancreatic cancer patients who were treated with upfront surgery between 2000 and 2012. Patients were then stratified by preoperative use of endoscopically placed stents (ERCP), percutaneous catheters (PTC), or no biliary drainage (NBD). The primary endpoint was overall survival (OS). Survival curves were calculated using the Kaplan-Meier method and the log-rank test. Multivariate analysis (MVA) was performed with a Cox regression model. Results: We identified 202 patients for the study (21 PTC; 89 ERCP; 92 NBD). Key differences between the 3 groups were mean pathologic tumor size (p=0.005), pathologic T3/4 (p =0.01), and pathologic N1 (p=0.007) status, with more aggressive pathologic features in PTC patients. PTC patients had a non-significant increase in rate of hepatic recurrences compared with ERCP and NBD patients (47.4% vs. 26.6% vs. 28.7%, respectively; p=0.20). PTC patients also had worse median and 3 year survival (21 months and 16%) compared to ERCP (23.3 months and 39%) and NBD patients (29 months and 45%, p=0.02). MVA revealed that PTC was an independent predictor of worse overall survival (HR 2.3[95% CI 1.3-4.0], p=0.005), along with pathologic tumor size (HR 1.1[1.0-1.3], p=0.008), nodes positive (HR 1.1[1.1-1.2], p=0.001), and post-operative CA19-9 >90 (HR 2.6[1.5-4.4], p=0.001). Conclusions: Patients with resectable pancreatic cancer who require a pre-operative PTC drain had a non-significant increase in hepatic recurrence rate and worse overall survival than patients who either had an ERCP stent placed or no biliary decompression prior to surgery. Given their worse prognosis, patients who require PTC placement might also benefit from neoadjuvant treatment with restaging prior to surgery.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors for locally advanced pancreatic cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 326-326
Author(s):  
Byung Min Lee ◽  
Seung Yeun Chung ◽  
Jee Suk Chang ◽  
Kyong Joo Lee ◽  
Si Young Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Pre Treatment

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR < 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR < 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR < 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR < 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR < 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR > 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.

Correlation of neutrophil lymphocyte ratio, platelet lymphocyte ratio and rate of change of CA 19.9 in predicting outcome for metastatic pancreatic cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 326-326
Author(s):  
Andrew Peter Dean ◽  
Dom Higgs ◽  
Adarsh Das ◽  
Madeline Rogers-Seeley ◽  
Sean Fennessy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Rate Of Change ◽  
Cox Proportional Hazards Model ◽  
Metastatic Pancreatic Cancer ◽  
Lymphocyte Ratio ◽  
Daily Rate ◽  
Ca 19.9

326 Background: CA19.9, NLR and PLR have all been proposed as prognostic in pancreatic cancer. We analysed correlation between NLR, PLR and rate of change of CA19.9. Methods: A total of 63 metastatic pancreatic cancer patients were identified from our database and evaluated retrospectively for blood count, NLR, PLR and serial CA19.9 levels during treatment. Daily Rate of Change of CA19.9 levels were calculated for the first 90 days (DRC90) of the patient’s treatment. Kaplan-Meir curves, univariate and multivariate Cox-regression analyses were calculated to assess the effects of these 3 markers on overall survival. Results: In a univariate analysis, PLR > 240, NLR > 5 and DRC90 > 0.4% were all significantly associated with deceased overall survival. The Cox proportional hazards model showed that NLR < 5 (HR 0.475, 95% CI 0.259 to 0.873, P = 0.017), PLR < 240 (HR 0.444, 95% CI 0.229 to 0.861, P = 0.016), and a DRC90 < 0.4% (HR 0.294, 95% CI 0.102 to 0.851, P = 0.024) were independent predictors of good prognosis (22.6 months vs. 9.6 months, 22.3 months vs 12.4 months and 23.9 months vs. 9.3 months respectively). In multivariate analysis, only a DRC90 < 0.4% was independently associated with a longer survival (HR 0.239, 95% CI 0.076 to 0.752, P = 0.014). The formula (F) {PLR + (NLRxNLR) + (DRC90 x 100)} was predictive for survival, as patients with F > 190 (HR 3.295, 95% CI 1.232 to 8.807, P = 0.017), having a significantly lower survival rate than patients with F < 190 (25.1 months vs. 10.6 months, log-rank P = 0.009). Conclusions: These findings indicate the prognostic utility of the rate of CA 19.9 decline - measured as a standardised daily percentage change in value over 90 days. Our data validates daily rate of change of CA 19.9 over 90 days as an independent variable that correlates with prognosis, independent of PLR and NLR. We also identified a novel formula - PLR + (NLRxNLR) + (DRC90 x 100) - as being predictive for survival. We would like to increase the sample size to further validate our initial findings and investigate possible relationships in combining these variables for better prognostication in metastatic pancreatic cancer.

Patient reported abdominal pain as a surrogate of the clinical benefit of tipifarnib in pancreatic cancer patients.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 275-275
Author(s):  
Antonio Gualberto ◽  
Catherine Rose Scholz ◽  
Eric Van Cutsem
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Abdominal Pain ◽  
Cancer Patients ◽  
Clinical Benefit ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Study Entry ◽  
Primary Study ◽  
Patient Reported

275 Background: Tumor CXCL12 expression identifies patients who may benefit from tipifarnib therapy. In pancreatic cancer, CXCL12 is known to decrease abdominal pain by inducing the migration of pain suppressing Schwann cells to tumor lesions. Given the association between CXCL12 and pain suppression, we investigated whether the absence of patient reported abdominal pain could be a surrogate of clinical benefit from tipifarnib in pancreatic cancer patients. Methods: We conducted a retrospective analysis of a randomized placebo-controlled trial comparing gemcitabine plus tipifarnib (GT) versus gemcitabine plus placebo (GP) in pancreatic adenocarcinoma patients. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine at standard dosing. Primary study end point was overall survival. Results: 688 patients were enrolled of whom 155 (22.5%) reported no abdominal pain at study entry, 81 received GT and 74 GP. Baseline characteristics were balanced in the subset of patients with no reported abdominal pain (GT,GP): median age (63,59), female gender (35%,43%), ECOG 0-1 (89%,90%), metastatic disease (64%,70%), 6-month weight loss >10% (48%,39%), 6-month jaundice history (51%,45%), and prior Whipple surgery (16%,13%). Subjects receiving GT who did not report abdominal pain at study entry had higher frequency of locally advanced disease (36% vs 24%) and 6-month jaundice (51% vs 38%), and lower frequency of lung (6% vs 14%) and peritoneum (4% vs 13%) metastases than those reporting pain. No differences in survival were observed in the overall study. Median overall survival for GT was 193 vs 182 days for GP. Notably, absence of abdominal pain at study entry was associated with higher median survival in the GT arm (no pain, pain): 305 vs 176 days, HR=0.52, p<0.0001, whereas no significant effect was observed in the control arm: 184 vs 182 days. A trend for better survival with GT was observed in subset of patients with no abdominal pain at study entry (GT,GP): 305 vs 184 days, p=0.058. Conclusions: Absence of abdominal pain may serve as a surrogate of clinical benefit from tipifarnib in pancreatic cancer. (Van Cutsem et al. JCO 2004;22:1430-8; NCT00005648; Trial Sponsor: J&J PRD). Clinical trial information: NCT00005648.

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