Chemotherapy at the end of life in colorectal and pancreatic cancer: Real-world data and trends over time.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18723-e18723
Author(s):  
Catherine Dunn ◽  
Belinda Lee ◽  
Jeremy David Shapiro ◽  
Rachel Wong ◽  
Grace Gard ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
End Of Life ◽  
Real World ◽  
Performance Status ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Chemotherapeutic Regimen ◽  
Trends Over Time ◽  
Line Of Therapy ◽  
Over Time

e18723 Background: Chemotherapy at the end of life (CEOL) is widely accepted as an indicator of aggressive care. However, the evidence is limited primarily to single-centre experiences, with no consensus regarding acceptable benchmarks for CEOL, nor how this may be changing over time and with novel treatment options. We describe ‘real world’ CEOL in two large, multisite Australian registries of metastatic colorectal cancer (mCRC) and both locally advanced and metastatic pancreatic cancer (PC). Methods: Data was analysed from the TRACC and PURPLE registries, two large prospective multisite Australian cancer registries collecting prospective demographic, tumour, treatment and outcome data for mCRC and PC respectively. We identified all decedents between May 2009 and November 2020, determined the proportion who died within 14 or 30 days of chemotherapy (14D / 30D), or within 30D after a new line of therapy, defined as the first cycle of a new treatment regimen. Using univariate analysis, we compared baseline demographic and clinicopathological variables and trends over time. Results: 1505 mCRC and 602 PC decedents were identified. 20.9% of decedents (21.6% mCRC and 19.3% PC) received chemotherapy within 30D, and 11.5% within 14D (12.3% mCRC and 9.6% PC). There were lower rates of 30D CEOL after the first cycle of a new line of therapy (4.3% mCRC and 5.7% PC). Rates of CEOL decreased over the study period for mCRC (median rate of initial 3-year period 28% versus 15% in last 3-year period), but remained largely static for PC (18.9% versus 17.9%). 30D CEOL was more likely with palliative than curative intent treatment (mCRC OR 1.6, 95% CI 1.14-2.25, p = 0.007, PC OR 5.3, 95% CI 1.6-17.8), and advanced rather than local disease in PC (PC OR 2.59, 95%CI 1.6-4.1, p < 0.001). There was a trend towards CEOL and poorer performance status (ECOG) across all groups, only significant for 30D CEOL mCRC (OR 1.51, 95% CI 1.04-2.2). There was no association between CEOL and patient age, gender, Charlson comorbidity score or lines of therapy. Conclusions: Real-world rates of CEOL are higher in our cohorts of mCRC and PC patients than historical benchmarks but comparable to contemporary reports, which may be due to a wider array of available active treatments. Overall rates are decreasing over time for mCRC but static for PC, which may reflect the poorer overall survival for PC and lack of new effective therapies. The lower rates of death after new lines of therapy may signify that CEOL is more likely with existing treatment regimens and that clinicians are less likely to initiate a new chemotherapeutic regimen at EOL.

Optimal indications for chemotherapy in elderly patients with unresectable pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 450-450
Author(s):  
Shoichi Nakazuru ◽  
Shoji Nakamori ◽  
Seiya Kato ◽  
Ayaka Shoji ◽  
Ryosuke Kiyota ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Performance Status ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Ct Scans ◽  
Unresectable Pancreatic Cancer ◽  
Cox Regression Analysis ◽  
Ecog Ps

450 Background: Pancreatic cancer is seen predominantly in elderly patients. Since many patients with pancreatic cancer have locally advanced unresectable tumors or distant metastases at diagnosis, they require chemotherapy. However, it is difficult to appropriately select elderly patients who are likely to benefit from chemotherapy. This study aimed to identify prognostic factors for elderly patients with unresectable pancreatic cancer treated with chemotherapy. Methods: We retrospectively analyzed the data of 191 patients with pancreatic cancer, aged ≥ 70 years, who had been diagnosed at our hospital between January 2006 and August 2016. Their overall survival (OS) was calculated using Kaplan-Meyer analysis. Prognostic factors were evaluated using Cox regression analysis. Results: Of the 191 patients, 52 patients with unresectable pancreatic cancer were treated with chemotherapy. Their median age was 76.5 years (range, 70–85 years). Twenty-two patients (42%) were men, and 44 (85%) had metastatic disease. Forty-one (79%) and 11 (21%) patients had ECOG performance status (PS) 0–1 and 2–3, respectively. Thirty-eight (73%), 10 (19%), and 4 (8%) patients received gemcitabine, gemcitabine-based combination regimens, and S-1, respectively, as first-line chemotherapy. The median OS was 219 days (range, 7–920 days). On univariate analysis, ECOG PS ≥ 2 (hazard ratio [HR], 4.37; P = 0.0005), carcinoembryonic antigen ≥ 10 ng/mL (HR, 2.32; P = 0.0162), serum AST ≥ 30 U/L (HR, 2.02; P = 0.0263), serum albumin < 3.0 g/dL (HR, 2.38; P = 0.0247), serum C-reactive protein ≥ 0.5 mg/dL (HR, 2.21; P = 0.0140), neutrophil-to-lymphocyte ratio ≥ 5.0 (HR, 3.25; P = 0.0066), and presence of ascites on computed tomography (CT) scans (HR, 3.02; P = 0.0016) were significantly associated with shorter survival times. On multivariate analysis, ECOG PS ≥ 2 (HR, 5.49; 95% confidence interval [CI], 2.18–13.32; P = 0.0005) and presence of ascites on CT scans (HR, 2.53; 95% CI, 1.20–5.24; P = 0.0148) were associated with poor OS. Conclusions: Elderly patients with unresectable pancreatic cancer who have a good performance status and do not show ascites on CT scans are likely to benefit from chemotherapy.

Neoadjuvant multimodal treatment of borderline resectable (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) in Mexico.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 454-454
Author(s):  
Vanessa Rosas Camargo ◽  
Edgar Omar Martos Armedáriz ◽  
Miriam Heidi Cisneros Cordero ◽  
ZULEYMA NIETO GARCIA ◽  
Christian Haydeé Flores Balcázar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Multimodal Treatment ◽  
Performance Status ◽  
Univariate Analysis ◽  
Single Agent ◽  
Locally Advanced ◽  
Pancreatic Head ◽  
Rank Test ◽  
R0 Resection

454 Background: Pancreatic cancer remains a highly lethal disease. There is no consensus on treatment sequences and chemotherapy (CT) regimen in BRPC and LAPC. Our aim was to describe the multimodal treatment and outcomes in our population. Methods: We retrospectively reviewed medical records of patients (pts) with BRPC/LAPC and histological diagnosis of adenocarcinoma evaluated at Instituto Nacional de Ciencias Médicas y Nutrición from January 2011-December 2016. Clinical and pathological variables at diagnosis and treatment were recorded. Overall survival (OS) was estimated using Kaplan-Meier method and compared by Log-rank test. Results: 69 pts were evaluated, 39% (27) did not receive treatment. We analyze 42 treated pts. BRPC 33%/LAPC 67%. Median age was 58.8 y/o, 54.8% were female. Symptoms at diagnosis: 79% abdominal pain, 76% weight loss, 55% jaundice. ECOG performance status (PS): 0 (17%), 1 (69%) and 2 (14%). Main location was pancreatic head (76%). Median laboratory values: total bilirubin 1.04 mg/dL (0.2-25), albumin 4.1 g/dL (2.4-5.1), CA 19.9 182.8 U/mL (0.8-4028). Laparotomy at diagnosis was performed in 21%. All pts received induction CT (iCT). FOLFIRINOX was the most common regimen (37%), followed by FOLFOX4 (34%). The best overall response with iCT was stable disease (62%), progressive disease was observed in 24%. iCT followed by chemoradiation (CRT) could be delivered to 48% (20/42). Capecitabine-based CRT was preferred (94%). Six pts (14%) underwent surgical resection after multimodal treatment (36% BRPC, 3.5% LAPC), 5 pts achieved R0 resection. The resection rate with single-agent iCT was 0% vs 20% with combination iCT. Median OS was 15.6 months (m): 14.4 m for BRPC and 15.5 m for LAPC. Median OS according iCT: gemcitabine 7.8 m, fluorouracil 13.7 m, FOLFOX4 15.5 m and FOLFIRINOX 24.6 m. Univariate analysis identified ECOG PS (0-1 vs 2, P = 0. 014) and age ( < 59 vs ³59, P = 0.002) as significantly associated with survival. Conclusions: Early administration of combination CT followed by CRT and/o surgical resection in selected pts improves oncological outcomes in pts with BRPC/LAPC. In pts with good PS, iCT with FOLFIRINOX is the preferred regimen given best results.

Trends in end-of- life (EOL) systemic oncologic treatment in contemporary clinical practice: Insights from real-world data.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 253-253
Author(s):  
Maureen Canavan ◽  
Xiaoliang Wang ◽  
Mustafa Ascha ◽  
Rebecca A. Miksad ◽  
Timothy N Showalter ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
End Of Life ◽  
Real World ◽  
Cost Of Care ◽  
Real World Data ◽  
Logistic Regression Models ◽  
Oncolytic Therapy ◽  
Immune Therapies ◽  
Using Data ◽  
Over Time

253 Background: Among patients with cancer, receipt of systemic oncolytic therapy near the end-of-life (EOL) does not improve outcomes and worsens patient and caregiver experience. Accordingly, the ASCO/NQF measure, Proportion Receiving Chemotherapy in the Last 14 Days of Life, was published in 2012. Over the last decade there has been exponential growth in high cost targeted and immune therapies which may be perceived as less toxic than traditional chemotherapy. In this study, we identified rates and types of EOL systemic therapy in today’s real-world practice; these can serve as benchmarks for cancer care organizations to drive improvement efforts. Methods: Using data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database we included patients who died during 2015 through 2019, were diagnosed after 2011, and who had documented cancer treatment. We identified the use of aggressive EOL systemic treatment (including, chemotherapy, immunotherapy, and combinations thereof) at both 30 days and 14 days prior to death. We estimated standardized EOL rates using mixed-level logistic regression models adjusting for patient and practice-level factors. Year-specific adjusted rates were estimated in annualized stratified analysis. Results: We included 57,127 patients, 38% of whom had documentation of having received any type of systemic cancer treatment within 30 days of death (SD: 5%; range: 25% - 56%), and 17% within 14 days of death (SD: 3%; range: 10% - 30%). Chemotherapy alone was the most common EOL treatment received (18% at 30 days, 8% at 14 days), followed by immunotherapy (± other treatment) (11% at 30 days, 4% at 14 days). Overall rates of EOL treatment did not change over the study period: treatment within 30 days (39% in 2015 to 37% in 2019) and within 14 days (17% in 2015 to 17% in 2019) of death. However, the rates of chemotherapy alone within 30 days of death decreased from 24% to 14%, and within 14 days, from 10% to 6% during the study period. In comparison, rates for immunotherapy with chemotherapy (0%-6% for 30 days, 0% -2% for 14 days), and immunotherapy alone or with other treatment types (4%-13% for 30 days, 1%-4% for 14 days) increased over time for both 30 and 14 days. Conclusions: End of life systemic cancer treatment rates have not substantively changed over time despite national efforts and expert guidance. While rates of traditional chemotherapy have decreased, rates of costly immunotherapy and targeted therapy have increased, which has been associated with higher total cost of care and overall healthcare utilization. Future work should examine the drivers of end-of-life care in the era of immune-oncology.

P14.69 Trends in postoperative chemoradiotherapy for Glioblastoma patients: a Danish cohort study

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii51-ii51
Author(s):  
A K Trip ◽  
V K Veluppillai ◽  
R H Dahlrot ◽  
T L Guldberg ◽  
A Muhic ◽  
...  
Keyword(s):  
Cohort Study ◽  
Real World ◽  
Performance Status ◽  
Concomitant Treatment ◽  
University Hospitals ◽  
Pronounced Increase ◽  
Evidence Based Treatments ◽  
Extent Of Surgery ◽  
Danish Cohort ◽  
Over Time

Abstract BACKGROUND Postoperative chemoradiotherapy (CRT), using conventional radiotherapy (convRT), has a key role in the treatment of glioblastoma (GBM) supported by level 1A evidence. In the past decade, evidence supporting hypofractionated radiotherapy (HFRT) has emerged. However, GBM patients in clinical trials are highly selected. Consequently, real-world patients may not be able to undergo evidence-based treatments. The aim of this retrospective Danish cohort study was to evaluate the utilisation of and compliance with postoperative CRT in real-world GBM patients over time. MATERIAL AND METHODS All adults (≥18 years) with newly diagnosed GBM (histology confirmed) between 2011 and 2018 were identified via the Danish Neuro-Oncology Registry, which was furthermore used to extract all data. Radiotherapy (RT) was classified as convRT (≤2 Gy/fr, planned dose 44–66 Gy) or HFRT (&gt;2 Gy/fr, planned dose 34 or 40 Gy). The utilisation of and compliance with CRT (only concomitant treatment assessed) was measured by intended and administered treatment, respectively. To assess trends, patients were grouped per year of diagnosis. Multivariable logistic regression was used to analyse the association of age (&lt;/≥70), sex, performance status (PS) before surgery and RT, tumour focality, extent of surgery, concomitant chemotherapy (CT), hospital (4 University Hospitals), and year of diagnosis, with convRT or HFRT. RESULTS The cohort consisted of 2153 patients. For the entire period, postoperative RT was planned in 1743 patients: utilisation of 81%, over time fluctuating between 77 and 84%. ConvRT was planned in 1428 patients (66%), with a steadily decreasing utilisation from 73% in 2011 to 52% in 2018. Of those, 1346 (94%) could complete RT as planned (over time fluctuating between 88–97%). In this group, the utilisation of and compliance with concomitant CT was 86% (fluctuating between 80–93%) and 73% (fluctuating between 47–84%), respectively. HFRT was planned in 315 patients (15%), with a utilisation of up to 26% in 2018, after a more pronounced increase since 2014. The compliance with HFRT was 93%, fluctuating between 85–100%. In this group, the utilisation of and compliance with concomitant CT was 33% (fluctuating between 0–47%) and 78% (fluctuating between 33–100%), respectively. The utilisation of HFRT compared to convRT was significantly associated with higher age, poorer PS before RT, multifocal tumour, less extensive surgery, less frequent concomitant CT, one hospital of RT treatment, and more recent diagnosis years. CONCLUSION The increased utilisation of HFRT is in line with emerging evidence during the cohort period. However, while HFRT was developed as a more convenient schedule for those with a poorer PS and older age, the overall utilisation of postoperative RT did not increase. Nor did the compliance with CRT increase in real-world Danish GBM patients.

Treatment patterns among patients with advanced urothelial carcinoma following discontinuation of PD1/L1 inhibitor therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 414-414
Author(s):  
Alicia K. Morgans ◽  
Simrun Kaur Grewal ◽  
Zsolt Hepp ◽  
Rupali Fuldeore ◽  
Shardul Odak ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Chart Review ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Unmet Need ◽  
Case Series ◽  
Treatment Patterns

414 Background: There are a lack of published real-world data on treatment patterns for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy. The objective of this study was to characterize the clinical characteristics and treatments among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1i therapy. Methods: We performed a retrospective chart review at 26 geographically diverse clinical sites in the US. Patients aged ≥18 years with histologically or cytologically confirmed urothelial carcinoma and radiographic evidence of metastatic or locally advanced disease were identified. Included patients had initiated and subsequently discontinued PD-1/L1i therapy in the 1L or 2L setting for la/mUC between May 15, 2016-July 31, 2018. All patients had follow-up through October 31, 2019. Data were summarized using descriptive statistics. Results: Among the 300 patients included in the chart review, 198 (66%) received PD-1/L1i therapy as 1L and 102 (34%) as 2L therapy. Mean (SD) age at la/mUC diagnosis was 69.4 (8.7) years, and a majority of patients were male (66.0%) and White (74.7%). Consistent with age, most patients (82.7%) had comorbidities at la/mUC diagnosis; 39.7% hypertension, 23.7% coronary artery disease, 17.7% pulmonary disease, and 9.3% renal disease. At initiation of therapy, a higher proportion of patients who received 1L PD-1/L1i therapy had an Eastern Cooperative Oncology Group performance status of 2 or more than patients who received 2L PD-1/L1i therapy (36.8% vs 22.5%, respectively). Following discontinuation of PD-1/L1i therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The most common subsequent therapies in 2L were gemcitabine monotherapy (24%), gemcitabine plus cisplatin or carboplatin (22%), PD-1/L1i therapy (22%), and taxane monotherapy (19%). The most common subsequent therapies received in 3L were taxane monotherapy (50%), pemetrexed (17%), and PD-1/L1i therapy (16%). Overall, switching from one PD-1/L1i therapy to another distinct PD-1/L1i therapy occurred in approximately 20% of patients, with “better efficacy/survival” noted by treatment teams as the most common reason for switching therapy among this subgroup. Conclusions: In this real-world case series, only a minority of patients with la/mUC who discontinued PD-1/L1i therapy received subsequent therapy. Among those that did, no clear standard of care was observed and approximately one-fifth of patients were treated with a second PD-1/L1i therapy after the first failed to control disease. Collectively, the data highlight significant unmet need for patients with la/mUC who discontinue PD-1/L1i therapy.

Kras mutation as a risk factor for venous thromboembolism in patients with metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16267-e16267
Author(s):  
Elena Serrano ◽  
Elizabeth Inga Saavedra ◽  
Maria Padilla Vico ◽  
Eduardo Perdomo ◽  
Maria Teresa Cano Osuna ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Venous Thromboembolism ◽  
Protective Factor ◽  
Performance Status ◽  
Locally Advanced ◽  
Venous Catheter ◽  
Serum Levels ◽  
Metastatic Pancreatic Cancer ◽  
Study Cohort ◽  
Significant Difference

e16267 Background: Venous thromboembolism (VTE) is a common complication in oncology patients. It has been reported that VTE increases morbidity and mortality in these patients. It’s prevalence in metastatic pancreatic cancer (mPC) ranges around 4-7.5% Preclinic studies suggest that the mutation of the KRAS oncogene (KRASm) is associated with a higher risk of VTE among patients with colorectal cancer. KRASm appears to increase the expression of tissue factor, a physiological trigger of coagulation that is found on the surface of tumor cells. This association has not been studied in mPC, where this mutation can be found in 90% of the cases. Our aim is to determine the prevalence and risk factors associated with VTE taking into consideration the status of KRAS. Methods: We conducted a retrospective study within a cohort of patients with mPC that had a determination of the KRAS status. These patients were treated at Medical Oncology between January 2017 and December 2020. We performed a descriptive and survival analysis of our sample. We also studied the prevalence of VTE among the. Results: Our study cohort was 88 patients (pts), 63 (61, 2%) men and 40 (38, 8%) women. The median age was 63 years (32-84). 19 pts (18, 4%) were KRAS wild type (KRASwt), 69 pts (67%) KRASm. There was no statistically significant difference in gender, age, performance status, comorbidities, primary tumor/metastases location, disease control rate and toxicity between KRASwt and KRASm. Median serum levels of Ca 19.9 were higher in KRASm (39.847 U/ml vs 2026 U/ml). At the time of diagnosis, 78 pts (88, 6%) were metastatic and 10 pts (11, 4%) were localized/locally-advanced. Most of metastatic pts (62/78) were KRASm (p = 0, 015). Most common histology (86, 4%) was adenocarcinoma. This histology was more frequent in KRASm, 61, 8% (p = 0, 02). At time of analysis, 72 pts (69, 9%) were dead, most of them (54, 4%) were KRASm (p = 0, 001). 31 pts developed VTE: 4 were KRASwt and 27 KRASm. The prevalence of VTE was 36, 3%. It was greater in KRASm (39, 1%) than in KRASwt (26, 3%). There were 7 cases of rethrombosis instead of anticoagulant treatment (1 KRASwt and 6 KRASm). KRASwt seems to be a protective factor in the development of VTE (OR 0, 55; CI 95% 0, 18-1, 71). The most common entity were VTE of splenoportomensenteric axis (16 pts), followed by pulmonary embolism, EP, (7 pts), deep venous thrombosis, DVT, (4 pts) EP + DVP (3 pts), thrombosis associated with central venous catheter (3 pts) and other locations (2 pts). There were no differences in VTE location between KRASwt and KRASm. The median overall survival (OS) was 12, 82 months (CI 95%: 7, 87-17, 78). It was higher in KRASwt (26 months; CI 95%: 12, 21-40, 48) than in KRASm (9, 8 months; CI 95%: 6, 07-13, 65). This difference was statistically significant (p = 0, 001). Conclusions: In our cohort, the prevalence of VTE is higher than de prevalence described in the literature and was greater in KRASm population. OS was significantly larger in KRASwt.

scholarly journals Role of Stereotactic Body Radiotherapy in the Treatment of Elderly and Poor Performance Status Patients With Pancreatic Cancer

2017 ◽  
Vol 13 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Lauren M. Rosati ◽  
Joseph M. Herman
Keyword(s):  
Pancreatic Cancer ◽  
Stereotactic Body Radiotherapy ◽  
Group Performance ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Poor Performance ◽  
Tumor Control ◽  
Poor Performance Status ◽  
Patient Reported

Literature on the management of nonmetastatic pancreatic ductal adenocarcinoma in patients who are elderly or have poor performance status is sparse. The median survival of this unique cohort of patients is < 6 months, and most patients are only offered single-agent gemcitabine or supportive care. Recently, adding nanoparticle albumin-bound paclitaxel to gemcitabine was shown to improve survival of patients with metastatic disease with Eastern Cooperative Group performance status of 2. Although standard chemoradiotherapy provides long-term locoregional control in locally advanced pancreatic cancer, it is difficult for this group of patients to tolerate 6 weeks of therapy. Stereotactic body radiotherapy (SBRT) can be delivered in only 3 to 5 days, does not require concurrent chemotherapy, and has limited toxicity, and tumor control rates appear to be equivalent to or better than those achieved with standard chemoradiotherapy. Additionally, SBRT has been shown to improve cancer-related pain and patient-reported quality of life. Given the favorable toxicity profile, SBRT seems like an obvious choice for patients who are elderly, have multiple comorbidities, or have poor performance status. Herein, we review the literature on SBRT in this unique patient population and discuss future directions.

The prognostic value of polymorphisms in the insulin-like growth factor receptor (IGFR) pathway in patients with locally advanced pancreatic cancer (LAPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
R. T. Shroff ◽  
M. M. Javle ◽  
X. Dong ◽  
V. S. Kumar ◽  
S. Krishnan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Induction Chemotherapy ◽  
Prognostic Value ◽  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
Cox Regression Analysis

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.

Application of a time-varying covariate model to the analysis of CA 19–9 as a biomarker for time-to-progression (TTP) and overall survival (OS) in patients with advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15545-e15545
Author(s):  
S. Boeck ◽  
R. P. Laubender ◽  
M. Haas ◽  
C. Klose ◽  
F. Kullmann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Time Varying ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Pre Treatment

e15545 Background: It remains unclear whether baseline CA 19–9 or CA 19–9 kinetics during chemotherapy may serve as predictive biomarker in patients (pts) with pancreatic cancer (PC). Methods: Main inclusion criteria for this retrospective multicenter analysis: histologically confirmed diagnosis of PC, treatment with first-line therapy, pre-treatment CA 19–9 level of > 5.2 U/ml. Analysis of CA 19–9 was exclusively performed using the Elecsys® assay (Roche Diagnostics). The effect of the pre- treatment CA 19–9 level on TTP and OS was modelled by Cox proportional hazards regression. The effect of CA 19–9 kinetics was also modelled by Cox proportional hazards regression where CA 19–9 was treated as time-varying covariate. When modelling CA 19–9 we developed univariate and multivariate Cox models where we selected additional predictors (e.g. performance status) using backward elimination performing likelihood ratio tests on a significance level of 0.05. Results: One-hundred and fifteen pts from 5 German centers were included. Median age was 63 years, 12% had locally advanced and 88% metastatic disease; 73 % of the pts were treated within prospective clinical trials. Median baseline CA 19–9 was 1059 U/ml (range 9.5–100000), median pre- treatment bilirubin 0.6 mg/dl. The median TTP in the study population was 4.4 months, median OS 9.4 months. Univariate analysis showed that the pre-treatment CA 19–9 level (as continuous variable, log [CA 19–9]) was significantly associated with TTP (HR 1.24, 95% CI 1.12–1.37, p<0.001) and OS (HR 1.16, 95% CI 1.06–1.28, p=0.002). These associations remained significant also within a multivariate analysis. For CA 19–9 kinetics during chemotherapy, data from 69 pts (TTP) and 84 pts (OS) were available, respectively; log [CA 19–9] kinetics were found to be a significant predictor for TTP in univariate (HR 1.44, 95% CI 1.25–1.67, p<0.001) and multivariate (HR 1.39, 95% CI 1.19–1.62, p<0.001) analyses, and also for OS (univariate: HR 1.34, 95% CI 1.20–1.49, p<0.001; multivariate: HR 1.39, 95% CI 1.23–1.57, p<0.001). Conclusions: According to this new statistical model, CA 19–9 may serve as a useful predictive biomarker in advanced PC. [Table: see text]

Updated results of the GEST study: Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer in Japan and Taiwan.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4035-4035 ◽  
Author(s):  
Akira Fukutomi ◽  
Takuji Okusaka ◽  
Kazuya Sugimori ◽  
Hideki Ueno ◽  
Tatsuya Ioka ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Primary Endpoint ◽  
Advanced Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Locally Advanced Disease ◽  
Phase Iii Study

4035 Background: The GEST study (Ioka et al. ASCO 2011, Abstract 4007) demonstrated the non-inferiority of S-1 to GEM with respect to the primary endpoint of overall survival (OS) in patients with pancreatic cancer (PC). We now report the updated results of this study. Methods: The GEST study was a randomized, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG Performance status (PS) of 0-1, and adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w), or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was OS, used to assess the non-inferiority of S-1 and the superiority of GS to GEM. Patient information was updated in July 2011. Results: At the time of this follow-up analysis, median follow-up was 29.8 months with 795 OS events, compared with 18.4 months with 710 OS events out of 832 patients at the previous analysis. Median OS was 8.8 months (95% CI: 8.0–9.7) in the GEM group and 9.7 months (95% CI: 7.6-10.8) in the S-1 group (HR=0.96, 97.5% CI: 0.79-1.17, p<0.001 for non-inferiority), which is consistent with prior results (HR=0.96, 97.5% CI: 0.78-1.18, p<0.001). In the GS group, median OS was 9.9 months (95% CI: 9.0-11.2). The HR was 0.91 (97.5%CI: 0.75-1.11, p=0.28 for superiority versus the GEM group). On subgroup analysis, GS was associated with a non-statistically significant trend toward better OS compared with GEM among patients with locally advanced disease and those with a PS of 1. Median OS was 12.7 months (95% CI: 9.7–14.9) in the GEM group and 15.9 months (95% CI: 13.0-19.7) in the GS group (HR=0.72, 95% CI: 0.51-1.03) among patients with locally advanced disease, and 6.2 months (95% CI: 4.9–8.3) in the GEM group and 9.6 months (95% CI: 8.0-10.9) in the GS group (HR=0.62, 95% CI: 0.46-0.83) among patients with a PS of 1. Conclusions: The non-inferiority of S-1 to Gem in terms of the primary endpoint of OS was reconfirmed. Monotherapy with S-1 can be used as one of the standard treatments for advanced PC. As for GS therapy, there is room for further investigation.

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