Pancreatic cancer: Survival in clinical trials versus the real world.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Reith Roy Sarkar ◽  
Rayna Matsuno ◽  
James Don Murphy
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Pancreatic Adenocarcinoma ◽  
Median Survival ◽  
Real World ◽  
Locally Advanced ◽  
The Real ◽  
Survival Differences

216 Background: Physicians often use clinical trial data to estimate expected survival for their patients, however clinical trial results may not generalize to a broader population. Given the need for accurate prognostication, we examined whether the survival of clinical trial pancreatic adenocarcinoma patients was similar to “real world” patients. Methods: We conducted a literature search using Pubmed to identify pancreatic adenocarcinoma Phase III trials published between 2005 and 2012. We excluded secondary or pooled analyses, trials with second-line treatments, and non-randomized studies. We compared clinical trial patients to a cohort of patients from the Surveillance, Epidemiology, and End Results (SEER) program, matching for diagnosis year, age and stage of disease. We evaluated for differences in median survival, 1-year survival, and 2-year survival. Results: We identified 27 trials (3 metastatic, 16 mixed metastatic and locally advanced, 3 locally advanced, and 5 resectable) that fit our search criteria, consisting of 8,438 patients. Compared to SEER the median survival was higher in 98% of the individual clinical trial arms by an average of 3.7 months (p = 0.001). The 1-year overall survival rate was higher in 100% of the clinical trial arms by an average of 12.3% (p <.0001). The 2-year overall survival was higher in 76% of the clinical trial arms by an average of 5.1% (p <.0001). The survival differences between SEER and clinical trials were greatest for patients with metastatic pancreatic cancer. Conclusions: We found that clinical trial patients have profoundly improved survival compared to patients in the SEER database, suggesting that clinical trial survival estimates may not generalize to “real world” patients with pancreatic cancer. Patient performance status, underlying comorbidity, and differences in treatment could not be assessed in SEER, though these factors likely explain a portion of the survival differences. These findings suggest that physicians should use caution when extrapolating survival estimates from clinical trials to the real world.

Survival among metastatic colorectal patients in clinical trials compared to the real world.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 673-673
Author(s):  
Ziwei Wang ◽  
Lindsay Hwang ◽  
James Don Murphy
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Median Survival ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
The Real ◽  
Clinical Trial Results

673 Background: Randomized clinical trials play a central role in clinical research though only a small fraction of patients partake in clinical studies. Questions thus arise regarding the generalizability of clinical trial results to the remainder of the population. This study evaluated whether patient survival from randomized clinical trials in metastatic colorectal cancer reflects real world outcomes. Methods: A Pubmed search was used to identify randomized phase III clinical trials of first-line treatment for metastatic colorectal cancer published between 2005 and 2010. We excluded secondary or pooled analyses, second-line treatments, non-metastatic patients, non-English language, and non-randomized studies. Thirty-one clinical trials met these criteria, comprised of 79 distinct clinical trial arms. Overall survival among clinical trial patients was compared to metastatic colorectal cancer patients within the Surveillance, Epidemiology, and End Results (SEER) program. Within SEER, we restricted the analysis time-period and age of patients to match the enrollment period and age of patients within each individual clinical trial. Results: The clinical trials enrolled a total of 16,614 patients. Among all clinical trial arms the median survival ranged from 6.7-62 months, 1-year survival ranged from 30-97%, and 2-year survival ranged from 6-88%. Compared to SEER, the median survival was higher in 95% of the individual clinical trial arms by an average of 5.4 months (p<0.0001). The 1-year survival was higher in 94% of the clinical trial arms by an average of 16.7% (p<0.0001). The 2-year survival was higher in 71% of the clinical trial arms by an average of 7.2% (p<0.0001). Conclusions: This study found substantially improved survival among clinical trial participants compared to patients in the SEER database suggesting that survival estimates from clinical trials may not generalize to the “real world.” Potential patient factors such as differences in underlying comorbidity, performance status, disease burden, as well as variation in treatment could not be addressed in this study, though these factors likely explain some of the observed survival differences.

Head-to-head comparison of first-line FOLFIRINOX versus gemcitabine plus nabpaclitaxel (GN) in advanced pancreatic cancer (APC): A target trial emulation using Canadian real-world data.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18713-e18713
Author(s):  
Devon J. Boyne ◽  
Darren Brenner ◽  
Alind Gupta ◽  
Eric Mackay ◽  
Paul Arora ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Survival ◽  
Real World ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Medical Decision ◽  
Target Trial ◽  
Real World Data ◽  
World Data

e18713 Background: When randomized trials are not available, observational real-world data can be used to emulate a (hypothetical) target trial. The procedure starts with the specification of the protocol of the target trial, whose components are then explicitly emulated using observational data. This approach prevents biases that are common when using more conventional methods for real-world data. Advanced pancreatic cancer represents an opportunity for trial emulation since two main frontline therapies, FOLFIRINOX and GN, have never been directly compared in a randomized fashion. The choice between the two regimens is largely based on physician discretion and patient preference rather than direct comparison of effectiveness. Methods: We emulated a target trial using linked data from the provincial cancer registry, electronic health records and various administrative databases from Alberta, Canada. Eligible individuals had locally advanced or metastatic pancreatic cancer diagnosed between Jan. 2015- Dec. 2018, no prior treatment, and adequate hematologic and serum creatinine values. They were followed from diagnosis until March 2020, death, or date of last known contact with the healthcare system. We estimated the effect of initiating FOLFIRINOX vs. GN within 8 weeks of diagnosis on overall survival. Cloning, artificial censoring, and inverse probability weighting were used to address unknown treatment assignment at baseline, non-adherence, and confounding. Adjusted Kaplan-Meier survival curves and hazard ratios were estimated. Results: Of 298 eligible individuals, 70 adhered to the FOLFIRINOX strategy and 147 to the GN strategy. The mean age was 65 years, 173 (58%) were male, and 247 (83%) had metastatic disease. The adjusted median survival, 1-year survival, and 2-year survival for FOLFIRNOX was 8.2 months (95% CI: 5.3 to 9.4), 36.9% (22.2 to 55.8), and 14.1% (4.8 to 32.2), respectively; and for GN was 4.8 months (3.3 to 5.3), 22.2% (13.6 to 35.9), and 4.7% (1.7 to 13.0), respectively. The adjusted difference in median survival was 3.4 months (0.6 to 11.1) and the adjusted hazard ratio was 0.79 (0.56 to 1.05). Conclusions: Target trial emulations can help to inform medical decision making in situations where head-to-head randomized trial data are unavailable or unfeasible. Findings from this real-world trial emulation suggest improved overall survival with FOLFIRINOX over GN.

Pre-SBRT metabolic tumor volume and total lesion glycolysis to predict survival in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 189-189
Author(s):  
Avani Satish Dholakia ◽  
Muhammad Ali Chaudhry ◽  
Jeffrey P. Leal ◽  
Daniel Tandel Chang ◽  
Siva P. Raman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Tumor Volume ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metabolic Tumor Volume ◽  
Total Lesion Glycolysis ◽  
Pet Scan ◽  
Locally Advanced Pancreatic Cancer

189 Background: Though prior studies have demonstrated the prognostic value of pre- and post-treatment positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer is yet to be established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiotherapy (SBRT). Methods: Thirty-two patients with LAPC received up to 3 doses of gemcitabine, followed by SBRT 6.6 Gy in 5 daily fractions, 33 Gy total, on a prospective clinical trial. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using an in-house software. Disease measurability was assessed at a threshold based on the liver standard uptake value (SUV) using the equation Livermean + (2 * Liversd). Median values of PET parameters were used as cutoffs when assessing their prognostic potential through univariate and multivariate Cox regression analyses. Results: Of the 32 patients in this study, the majority were male (N=19, 59%), 65 years or older (N=21, 66%), and had tumors located in the pancreatic head (N=27, 84%). Twenty-seven patients (85%) received induction gemcitabine prior to SBRT per protocol. Median overall survival for the entire cohort was 18.8 months (95% CI, 15.7-22.0). An MTV of 26.8 cm3 or greater (HR 4.46, 95% CI 1.64 to 5.88, p < 0.003) and TLG of 70.9 cm3 or greater (HR 3.08, 95% CI 1.18 to 8.02, p < 0.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19 to 22.21, p=0.029) and TLG (HR 3.34, 95% CI 1.07 to 10.48, p=0.038) remained independent prognostic factors for overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG yield prognostic information on overall survival in patients with LAPC and may assist in tailoring therapy. Clinical trial information: NCT01146054.

Nab-paclitaxel plus gemcitabine followed by radiotherapy with concurrent 5-FU in locally advanced unresectable pancreatic cancer: A Western Australian experience.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 430-430 ◽  
Author(s):  
Andrew Peter Dean ◽  
Nigel Spry ◽  
Alycea McGrath
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Median Survival ◽  
Locally Advanced ◽  
Radical Resection ◽  
Response To Therapy ◽  
Unresectable Pancreatic Cancer ◽  
Radical Radiotherapy ◽  
Metastatic Setting ◽  
Western Australian

430 Background: The optimal management of patients with locally advanced unresectable pancreatic cancer is unclear. In the metastatic setting, superior response rates have been seen with nab-paclitaxel plus gemcitabine compared to gemcitabine alone. We investigate the efficacy and safety of nab-paclitaxel plus gemcitabine followed by radical radiotherapy with concurrent 5-FU in patients with locally advanced unresectable pancreatic adenocarcinoma. Methods: A retrospective review was conducted of all patients with locally advanced unresectable pancreatic cancer treated with nab-paclitaxel plus gemcitabine, the majority proceeding to radical radiotherapy with concurrent 5-FU, at two large Western Australian metropolitan hospitals from January 2009 to December 2014. Charts were reviewed to obtain patient characteristics, efficacy and tolerability. Kaplan-Meier analysis was utilised to obtain survival curves. Results: Forty-two patients were identified as having locally advanced unresectable pancreatic adenocarcinoma, receiving nab-paclitaxel plus gemcitabine to a mean number of 5 cycles, the majority requiring dose reductions. Of these, thirty proceeded to radical radiotherapy; the majority receiving 3DCRT, 54 Gy, with concurrent 5-FU. Seven had sufficient response to therapy to be offered radical resection. Six went on to radical resection, all with R0 or close resection margins (2 with complete response). Median length of stay following surgery was 18 days, and there were no perioperative deaths. The median survival for patients proceeding with surgery was 30 months. Median survival was 23 months for those treated with chemoradiotherapy, and 10 months with chemotherapy alone. Conclusions: This retrospective investigation demonstrates that nab-paclitaxel plus gemcitabine followed by radical radiotherapy with concurrent 5-FU is a tolerable treatment option with encouraging results for patients with locally advanced unresectable pancreatic cancer. The R0 resection rate in patients that had adequate response to allow for radical resection is promising. Further studies are warranted.

The rate of tumor growth, g, as a biomarker for overall survival (OS) in prostate cancer (PC) in clinical trials as well as in real-world data from the Veterans Administration Medical Centers (VAMCs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5074-5074
Author(s):  
Harshraj Leuva ◽  
Mengxi Zhou ◽  
Julia Wilkerson ◽  
Keith Sigel ◽  
Ta-Chueh Hsu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Tumor Growth ◽  
Real World ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Real World Data ◽  
World Data

5074 Background: Novel assessments of efficacy are needed to improve determination of treatment outcomes in clinical trials and in real-world settings. Methods: Cancer treatments usually lead to concurrent regression and growth of the drug-sensitive and drug-resistant fractions of a tumor, respectively. We have exploited novel methods of analysis that assess these two simultaneous processes and have estimated rates of tumor growth ( g) and regression ( d) in over 30,000 patients (pts) with diverse tumors. Results: In prostate cancer (PC) we have analyzed both clinical trial and real-world data from Veterans. Using clinical trial data from 6819 pts enrolled in 15 treatment arms we have established separately and by combining all the data that g correlates highly (p<0.0001) with overall survival (OS) – slower g associated with better OS. In PC, abiraterone (ABI) and docetaxel (DOC) are superior to placebo, prednisone and mitoxantrone. ABI (median g =0.0017) is superior to DOC ( g=0.0021) in first line (p=0.0013); and ABI in 2nd line ( g=0.0034) is inferior to ABI in 1st line ( g=0.0017; p<0.0001). Finally, using combined clinical trial data as a benchmark we could assess the efficacy of novel therapies in as few as 30-40 patients. Amongst 7457 Veterans, the median g on a taxane ( g=0.0022) was similar to that from clinical trials ( g=0.0012). Although only 258 Veterans received cabazitaxel (CAB), g values for CAB ( g=0.0018) and DOC ( g=0.0023) were indistinguishable (p=0.3) consistent with their identical mechanism of action. Finally, outcomes with DOC in African American (AA) ( g=0.00212) and Caucasian ( g=0.00205) Veterans were indistinguishable (p=0.9) and comparable across all VAMCs. Conclusions: The rate of tumor growth, g, is an excellent biomarker for OS both in clinical trials and in real-world settings. g allows comparisons between trials and for large trial data sets to be used as benchmarks of efficacy. Real-world outcomes in the VAMCs are similar to those in clinical trials. In the egalitarian VAMCs DOC efficacy in PC is comparable in AA and Caucasian Veterans -- indicating inferior outcomes reported in AAs are likely due to differential health care access, not differences in biology.

Real-world treatment and outcomes of frontline chemotherapy in patients with metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16249-e16249
Author(s):  
Salwan Al Mutar ◽  
Muhammad Shaalan Beg ◽  
Eric Hansen ◽  
Andrew J. Belli ◽  
Maegan Vaz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Real World ◽  
Univariate Analysis ◽  
The United States ◽  
Metastatic Pancreatic Cancer ◽  
Future Research ◽  
Real World Data ◽  
The Real ◽  
The Impact

e16249 Background: The difference between the FOLFIRINOX and gemcitabine/nab-paclitaxel (GnP) regimens’ clinical trial designs limit the ability to generate cross-study comparisons. Therefore, there is a significant need to understand the impact of various demographic and clinical characteristics on the effectiveness of these systemic therapies in the real-world treatment setting. This study seeks to compare the real-world outcomes of patients with metastatic pancreatic cancer treated with frontline FOLFIRINOX or GnP. Methods: Patients with primary metastatic pancreatic cancer who received first-line (1L) FOLFIRINOX or GnP were identified in the COTA real-world database. The COTA database is a de-identified database of real-world data (RWD) derived from the electronic health records of healthcare providers in the United States. Real-world overall response rate (rwORR) was calculated as the proportion of patients achieving complete response (CR) or partial response (PR). Overall survival (OS) was calculated using the Kaplan-Meier method and multivariate analyses utilized Cox proportional hazards. Results: The overall qualified cohort (n=236) was stratified by 1L FOLFIRINOX (n=109) or GnP (n=127). Select patient characteristics are shown in table. Patients treated with 1L FOLFIRINOX showed greater rwORR as compared to those treated with GnP (68.8% vs. 55.9%, p=0.04). Additionally, patients treated with 1L FOLFIRINOX had longer median OS (14.4 vs 11.4 mos, respectively). In univariate analysis, patients treated with GnP had a greater chance of mortality (HR: 1.3, 95% CI: 1.0, 1.8, p=0.05). This relationship strengthened in multivariate analysis (GnP treated HR: 1.6, 95% CI: 1.1, 2.1, p=0.01). Conclusions: Due to lack of enrollment of representative patients in clinical trials and in the absence of a comparative clinical trial, real-world experience with chemotherapy regimens provide critical insights on the outcome of treatments. In our cohort, patients treated with frontline GnP had a significantly greater chance of mortality as compared to patients treated with frontline FOLFIRINOX. The FOLFIRINOX cohort also showed greater rwORR. Future research will continue to expand on treatment patterns in subsequent lines of therapy, as well as emerging therapy types, in order to better understand the optimal treatment sequence in metastatic pancreatic cancer.[Table: see text]

scholarly journals Conversion Therapy of Unresectable Pancreatic Cancer: A Retrospective Study of the Real World

2021 ◽  
Author(s):  
Mingxing Wang ◽  
Pengfei Zhu ◽  
Zheling Chen ◽  
Liu Yang
Keyword(s):  
Pancreatic Cancer ◽  
Retrospective Study ◽  
Real World ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Conversion Therapy ◽  
The Real ◽  
Zhejiang Provincial

Abstract Objective: A retrospective study of the real world was conducted to analyze whether patients with unresectable pancreatic cancer (URPC) can benefit from conversion therapy, and to screen out pancreatic cancer patients who are suitable for conversion therapy.Patients and Methods: Inquired about patients with URPC who visited Zhejiang Provincial People's Hospital from January 2015 to April 2021. We selected 25 patients with URPC who underwent conversion therapy, and 19 patients with locally advanced pancreatic cancer (LAPC) who directly underwent surgery to conducted a retrospective analysis. Results: The median overall survival (OS) of 25 patients with URPC who received conversion therapy was 28 months (95%CI: 15.46-40.54 months), and the median progression-free survival (PFS) was 12 months (95%CI: 9.26-14.74 months). The curative resection (R0) rate was 84% (22/25).Conclusions: Conversion therapy improves the R0 rate of patients with URPC, and prolongs OS and PFS.

Clinical outcomes of FOLFIRINOX and gemcitabine/nab-paclitaxel in the real world setting.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 440-440 ◽  
Author(s):  
Fernando Franco Franco ◽  
Camara Juan C ◽  
Jose Ignacio Martin Valades ◽  
David Marrupe ◽  
David Gutierrez Abad ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Real World ◽  
Survival Data ◽  
Locally Advanced ◽  
Developed Countries ◽  
First Line ◽  
The Real ◽  
Risk Of Death ◽  
Ca 19.9

440 Background: The incidence of pancreatic cancer is increasing in developed countries. Though FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) are associated with increased toxicity and are addressed to a well selected population, there seems to have been a rapid incorporation of these regimens in the real world. Overall survival (OS) was 11.1 months for FFX and 8.5 months for GNP. Survival rate at 18 m with FFX was 18.6%; at 24 m with GNP was 9%. Questions have arisen about external validity of original trials and how could these regimens impact overall survival since they are available nowadays for second line settings. Methods: This is a retrospective study. The Departments of Pharmacy of 5 Spanish hospitals generated the listings of patients (pts) treated in first line with the new regimens, namely FFX or GNP. To avoid bias related to non-prospective data collection, we restricted the analysis to survival data, serious toxicity and 2nd line options. Results: From Jan 2012 to Dec 2016, a total of 136 pts (M/F 52/48 %) were treated. Med age 63 y (38-83 y), 95% adenocarcinoma. 48% head of pancreas. ECOG 88% 0-1. 36 % locally advanced and 64% metastatic. 88% had liver mets. In the 1st line 64% were treated with FFX and 36% with GNP. 5 (3,7%) pts died in the first 3 months of treatment, because of infectious complications. 16 pts were operated after chemotherapy. 60% of the pts could receive a 2nd line (43% GNP, 25% FFX, 32% other). 27 pts (19.8%) were treated with a 3rd line. More pts treated with FFX required G-CSF (85% vs 15%). The median OS was 13 months with no differences between regimens. Survival rate at 30 months was 25% for both regimens. Elevated Ca 19.9 levels and Neutrophil-Lymphocyte ratio (NLR) increased the risk of death during the first-line. Conclusions: Originally reported OS is not only reproduced but improved in the real world despite a less strict inclusion of pts. 25% of patients remain alive 30 months after diagnosis. Superiority could not be demonstrated for any of the schemes. The availability of both regimens seems to dilute the potential differences and it is not so important the election of the 1st line. Both NLR and Ca 19.9 level predicted risk of death during the 1st line impairing the possibility of being treated in 2nd line.

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