Identification of prognostic factors for patients with advanced pancreatic cancer by proteomics

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4615-4615
Author(s):  
J. Matsubara ◽  
M. Ono ◽  
H. Ueno ◽  
T. Okusaka ◽  
J. Furuse ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prediction Model ◽  
Statistical Significance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Information Criterion ◽  
Survival Prediction ◽  
Current Standard ◽  
Ecog Performance Status ◽  
Wbc Count

4615 Background: Gemcitabine monotherapy is the current standard for patients with advanced pancreatic cancer (PC). Its efficacy, however, varies significantly depending on individuals. This study was aimed at discovering a new diagnostic biomarker that can estimate the outcome of patients after receiving the therapy. Methods: All patients included in this study (304 patients) had metastatic PC and received at least two cycles of gemcitabine monotherapy. We compared the baseline plasma proteome between representative 29 short-term survivors (survived for less than 100 days) and 31 long-term survivors (survived for more than 400 days) using quantitative mass spectrometry (MS). Results: Among a total of 45,277 peptide peaks, we identified 637 peaks whose intensities were significantly different (p<0.001, Welch's t-test). The 2 MS peaks with the highest statistical significance (p=2.57×10-4 and 5.03×10-4) were revealed to be derived from α1-antitrypsin (AT) and α1-antichymotrypsin (ACT), respectively, by tandem MS. The levels of AT and ACT, WBC count, platelet count, alkaline phosphatase, and ECOG performance status were selected using a forward stepwise procedure by Akaike's information criterion, and a scoring system (nomogram) was constructed to estimate the prognosis of individual patients. Among the selected parameters the AT level was found to be the second most significant contributor to the nomogram (p=0.0003; Table ). This survival prediction model was internally validated using a bootstrap approach with 200 resamples. Conclusions: Our survival prediction model including values of AT and ACT seems to have high practical utility and may lead to tailoring the treatment of patients with advanced PC. Modification of therapeutics may need to be taken into consideration for patients with increased AT and ACT. [Table: see text] [Table: see text]

Early tumor shrinkage as a predictor of favorable outcomes in patients (pts) with advanced pancreatic cancer treated with FOLFIRINOX.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 237-237
Author(s):  
Yasuhiro Kaga ◽  
Yu Sunakawa ◽  
Yutaro Kubota ◽  
Teppei Tagawa ◽  
Taikan Yamamoto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Tumor Shrinkage ◽  
Current Standard ◽  
Early Tumor Shrinkage ◽  
Early Tumor

237 Background: Results from the phase III PRODIGE 4/ACCORD 11 trial provided one of current standard regimens for advanced pancreatic cancer (PC), consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX), which has superior response rate (RR) and survival benefit even with severe toxicity (Thierry C, et al. N Engl J Med 2011;364:1817-1825). There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in PC. We therefore analyzed retrospectively whether the ETS will predict outcomes in pts with PC treated with FOLFIRINOX therapy. Methods: Advanced PC pts with ECOG PS of 0 or 1, who received FOLFIRINOX as 1st- or 2nd-line treatment between November 2012 and July 2015 in 3 institutes of Showa University were included in this analysis. ETS was defined as a reduction ≥ 20% of target lesions’ diameters measured at 8 weeks from treatment start. We evaluated the association of ETS with progression-free survival (PFS) and overall survival (OS) but also addressed the correlation between outcomes and DpR, which was percentage of maximal tumor shrinkage observed at the nadir diameter compared with baseline. Results: Fifty-nine PC pts with median age of 63 (range 34-76) years and males of 68% were enrolled: 80% of pts had metastatic disease. In the population, RR, median PFS, and OS were 28%, 5.4 months, and 10.7 months, respectively. Among 46 (78%) evaluable pts for the ETS, 12 (26%) pts experienced ETS. The PFS was significantly longer in pts with ETS compared to pts with no ETS (9.0 vs. 4.2 months, HR 0.43, 95%CI 0.17-0.96, log-rank P= 0.045). Moreover, pts with ETS had a better OS although no statistical significance (HR 0.53, log-rank P= 0.25). Median DpR was 11.1% (from -75.7 to 100), and the correlation of DpR with clinical outcome was observed (P= 0.024 for PFS, P= 0.22 for OS). Conclusions: This retrospective analysis suggests that the early response to FOLFIRINOX treatment may predict better outcomes in pts with advanced PC. The ETS may serve as a novel predictor of prolonged survival time in PC pts treated with FOLFIRINOX.

Clinical significance of elevation of the serum IL-6 level in patients with advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 181-181
Author(s):  
S. Mitsunaga ◽  
M. Ikeda ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Volume ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Japanese Version ◽  
Serum Levels ◽  
Ecog Performance Status ◽  
Reactive Protein ◽  
Treatment Naïve ◽  
Median Change

181 Background: IL-6, one of the pro-inflammatory cytokines, is a recognized mediator of cachexia and cancer cell invasion. It has been reported that elevation of the serum IL-6 level may be associated with deterioration of the clinical condition and tumor progression in advanced pancreatic cancer (PC) patients. The aim of this study was to clarify the clinical features of increased serum IL-6 levels in patients with advanced PC receiving chemotherapy. Methods: Patients with treatment-naïve unresectable PC and no obvious infectious conditions were eligible for this study. Serum levels of IL-6 were measured by an electrochemiluminescence assay. Symptoms were rated numerically from 0 to 10 using the Japanese version of the M. D. Anderson Symptom Inventory. Tumor volume was calculated as the sum of the long diameters of the tumors. The measurements were performed before chemotherapy and at one month after the start of chemotherapy. Results: A total of 87 patients (male/female: 41/46; ECOG performance status: 0/1/2: 59/26/1; media age: 66 years) were enrolled; all patients were administered systemic chemotherapy (gemcitabine [GEM]/GEM+S-1/GEM+other/S-1: 52/11/9/15). The median serum level of IL-6 was 1.3 pg/mL before chemotherapy (at baseline) and 1.8 pg/mL at one-month after the start of chemotherapy. The median change of IL-6 from the baseline was +0.18 pg/mL. Patients with increase of the serum IL-6 level by more than 0.18 pg/mL were assigned to the elevated IL-6 group (n=42; median change in IL-6: +1.66 pg/mL). The elevated IL-6 group showed more sadness (p=0.019), numbness (p=0.008), and gain of body weight (p=0.016) at the baseline as compared to the non-IL-6-elevated group (n=42; median change in IL-6: -0.27 pg/mL). Comparison of the elevated and non-IL-6-elevated groups revealed a greater degree of increase in the tumor volume (p=0.015), deterioration of nausea (p=0.046) and vomiting (p=0.028), neutrophilia (p=0.004), and elevation of the serum C-reactive protein (p=0.011) in the elevated IL-6 group than in the non-IL-6-elevated group. Conclusions: Elevation of the serum IL-6 level may be associated withsymptom deterioration, increase of the tumor mass, and inflammatory reaction in patients with advanced PC. No significant financial relationships to disclose.

Phase I trial of enzalutamide in combination with gemcitabine and nab-paclitaxel for the treatment of advanced pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 467-467
Author(s):  
Amit Mahipal ◽  
Gregory M. Springett ◽  
Nancy Burke ◽  
Barbara Bertels ◽  
Georgine Wapinsky ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Level ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Treatment Standard ◽  
Cancer Models ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Grade 3

467 Background: Despite recent advances, patients with metastatic pancreatic cancer have a very poor prognosis with a median survival of less than 1 year. Sex steroid hormones may play an important role in the growth and progression of pancreatic cancer. Anti-androgen drugs have demonstrated to have activity in pre-clinical pancreatic cancer models. In this Phase 1a/Ib trial, we evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel. Methods: Pts with histologically confirmed metastatic pancreatic adenocarcinoma were included in this trial as a first-line treatment. Standard 3+3 dose escalation design was used to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg daily. Gemcitabine 1,000 mg/m2 was administered IV on days 1, 8 and 15 of 28-day cycle. The dose of nab-paclitaxel was 125 mg/m2 IV on days 1, 8 and 15. The DLT period was 28-days or until the beginning of the second cycle. Imaging studies were performed every 2 cycles. Results: Eight pts with stage IV pancreatic cancer have been enrolled in this trial, 5 pts at the first dose level and 3 pts at the second dose level. The median age was 64 years (50-80 years). All pts were male with an ECOG performance status of 1. Five pts had liver metastases. One patient was non-evaluable for DLT. No DLTs have been observed. Grade 3 treatment related AEs include febrile neutropenia (n=1), Neutropenia (n=1), ALT elevation (n=1). Grade 2 anemia and thrombocytopenia was seen in one patient. Grade 1 AEs included anemia (n=2), neutropenia (n=4), thrombocytopenia (n=3), diarrhea (n=1), fatigue (n=2), pruritis (n=1), nausea (n=1), hyponatremia (n=1) and AST elevation (n=1). Three pts had restaging studies performed and all had stable disease by RECIST criteria. There were decreases in size of target lesions in all the 3 patients along with a decrease in CA 19-9 levels. Conclusions: Enzalutamide at the dose of 160 mg daily is safe to administer in combination with gemcitabine and nab-paclitaxel. No unexpected toxicity has been observed. Cytopenias secondary to chemotherapy is common. Preliminary signals of efficacy were observed with this combination. Clinical trial information: NCT02138383.

scholarly journals Identification of a Predictive Biomarker for Hematologic Toxicities of Gemcitabine

2009 ◽  
Vol 27 (13) ◽  
pp. 2261-2268 ◽  
Author(s):  
Junichi Matsubara ◽  
Masaya Ono ◽  
Ayako Negishi ◽  
Hideki Ueno ◽  
Takuji Okusaka ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Statistical Significance ◽  
Advanced Pancreatic Cancer ◽  
Area Under The Curve ◽  
Predictive Ability ◽  
Predictive Biomarker ◽  
Severe Neutropenia ◽  
Current Standard ◽  
Grade 3

PurposeGemcitabine monotherapy is the current standard for patients with advanced pancreatic cancer, but the occurrence of severe neutropenia and thrombocytopenia can sometimes be life threatening. This study aimed to discover a new diagnostic method for predicting the hematologic toxicities of gemcitabine.Patients and MethodsUsing quantitative mass spectrometry (MS), we compared the baseline plasma proteomes of 25 patients who had developed severe hematologic adverse events (grade 3 to 4 neutropenia and/or grade 2 to 4 thrombocytopenia) within the first two cycles of gemcitabine with those of 22 patients who had not (grade 0).ResultsWe identified 757 peptide peaks whose intensities were significantly different (P < .001, Welch t test) among a total of 60,888. The MS peak with the highest statistical significance (P = .0000282) was revealed to be derived from haptoglobin by tandem MS. A scoring system (nomogram) based on the values of haptoglobin, haptoglobin phenotype, neutrophil count, platelet count, and body-surface area was constructed to estimate the risk of hematologic adverse events (grade 3 to 4 neutropenia and/or grade 2 to 4 thrombocytopenia) with an area under curve value of 0.782 in a cohort of 166 patients with pancreatic cancer. Predictive ability of the system was confirmed in two independent validation cohorts consisting of 87 and 52 patients with area under the curve values of 0.655 and 0.747, respectively.ConclusionAlthough the precise mechanism responsible for the correlation of haptoglobin with the future onset of hematologic toxicities remains to be clarified, our prediction model seems to have high practical utility for tailoring the treatment of patients receiving gemcitabine.

Association of interleukin-6 levels and neutropenia during gemcitabine monotherapy for advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 178-178 ◽  
Author(s):  
H. Okuyama ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Inflammatory Cytokines ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Severe Neutropenia ◽  
Ecog Performance Status ◽  
Tnf Α ◽  
Low Serum ◽  
Pro Inflammatory Cytokines

178 Background: Neutropenia is an important dose-limiting toxicity of gemcitabine (GEM) in patients with advanced pancreatic cancer (PC). Serum haptoglobin, regulated by pro-inflammatory cytokines, is a predictor of neutropenia in PC patients under treatment with GEM. We conducted this study with the aim of identifying the association between serum levels of haptoglobin and cytokines and the risk of development of neutropenia in advanced PC patients receiving GEM therapy. Methods: Serum levels of haptoglobin and pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2β, IL-6, IL-8, IL-10, IL-12, TNF-α) were measured in 55 patients with advanced PC. All patients (median age: 67 years, male/female: 26/29, ECOG performance status: 0/1/2: 32/21/2,) received GEM monotherapy as the initial treatment for PC. The severity of neutropenia within the first 90 days of the GEM treatment was graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Categorical or and noncategorical data were compared using Student's t test. Multivariate regression analysis was performed using logistic regression modeling. The significance level was set at p<0.05. Results: Grade 0 to 2 (G0/1/2) and grade 3 to 4 (G3/4) neutropenia were observed in 32 patients (58.2%) and 23 patients (41.8%), respectively. The G3/4 neutropenia group showed low serum levels of haptoglobin (mean 144.4 mg/dl vs. 186.7 mg/dl, p=0.097), IL-1β (mean 0.07 pg/ml vs. 0.24 pg/ml, p=0.044), IL-6 (mean 1.13 pg/ml vs. 6.43 pg/ml, p=0.002), IL-8 (mean 18.4 pg/ml vs. 44.8 pg/ml, p=0.015), and TNF-α (mean 6.28 pg/ml vs. 8.86 pg/ml, p=0.017) as compared to the G0/1/2 neutropenia group. Multivariate analysis revealed that only low serum IL-6 was significantly associated with the development of G3/4 neutropenia (OR=0.081, p=0.0011). Conclusions: Low serum IL-6 level was associated with severe neutropenia. Thus, circulating IL- 6 levels may be a predictor of the development of severe neutropenia in advanced PC patients receiving GEM therapy. No significant financial relationships to disclose.

scholarly journals Prognostic Factors for Advanced Pancreatic Cancer Treated with Gemcitabine Plus S-1: Retrospective Analysis and Development of a Prognostic Model

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 57 ◽  
Author(s):  
Ching-Fu Chang ◽  
Pei-Wei Huang ◽  
Jen-Shi Chen ◽  
Yen-Yang Chen ◽  
Chang-Hsien Lu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Factors ◽  
Prognostic Model ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Tumor Stage ◽  
Albumin Level ◽  
Survival Prediction ◽  
Pre Treatment ◽  
Clinical Experiments

Gemcitabine plus S-1 (GS) is commonly used to treat advanced pancreatic cancer (APC) in Asia. Few clinical experiments have demonstrated the clinical efficacy of GS in routine clinical practice. We aimed to identify the prognostic factors and develop a prognostic model for survival prediction in patients with APC, treated with GS. Records of 111 patients with newly diagnosed APC who received first-line palliative GS chemotherapy during 2010–2016 in Taiwan were analyzed retrospectively. Univariate and multivariate analyses were performed for the identification of prognostic factors. A prognostic model using prognosticators from the multivariate analysis was developed for survival prediction. The median overall survival (OS) for the cohort was 9.3 months (95% confidence interval [CI], 8.0–10.6). The prognostic model was constructed based on four independent prognosticators: performance status, tumor stage, pre-treatment albumin level, and neutrophil-to-lymphocyte ratio. Patients were categorized by tertiles into good, intermediate, and poor prognostic groups. The median OS values for each of these groups were 21.1 (95% CI, 8.2–33.9), 9.2 (95% CI, 8.3–10.1), and 5.8 months (95% CI, 4.4–7.1; log-rank p < 0.001), respectively. The bootstrapped corrected C-index of this model was 0.80 (95% CI, 0.71–0.89). The developed model was robust and could accurately predict survival in this population, and can assist clinicians and patients in survival discrimination and the determination of appropriate medical care goals. Additional research is needed to externally validate the model’s performance.

Phase II Study of Oral L-Leucovorin, 120-Hour Fluorouracil Infusion and Carboplatin in Advanced Pancreatic Cancer

1996 ◽  
Vol 82 (6) ◽  
pp. 573-575 ◽  
Author(s):  
Marco Colleoni ◽  
Patrizia Nelli ◽  
Giovanni Vicario ◽  
Francesca Pancheri ◽  
Gigliola Sgarbossa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Carcinoma ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Treatment Schedule ◽  
Time To Progression ◽  
Ecog Performance Status ◽  
Advanced Pancreatic Carcinoma

Background No effective chemotherapy has been developed for patients with metastatic pancreatic cancer. Encouraging results have been reported with the combination of cisplatin and fluorouracil infusion. The aim of the study was to test the activity of oral L-leucovorin, carboplatin and fluorouracil infusion in untreated pancreatic cancer patients. Patients and Methods Patients with advanced pancreatic carcinoma were treated with carboplatin (300 mg/m2 on day 1), L-leucovorin (5 mg/m2 twice a day on days 1-5), and fluorouracil (1,000 mg/m2 as a 120-hr infusion on days 1-5), cycles being repeated every 21 days. Results Nine patients were included and were assessable for response and side effects. All patients had measurable disease and an ECOG performance status of 0-2. No patient achieved partial remission, 3 had stable disease, and 6 progressive disease. Median time to progression was 2 months (range, 2-8), and median survival was 4 months (range, 3-12). Toxicity consisted of mucositis, diarrhea and neutropenia. Conclusions Patients with metastatic pancreatic carcinoma do not benefit from this treatment schedule.

A phase II trial of oxaliplatin plus capecitabine (xelox) as second line therapy for patients with advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4119-4119 ◽  
Author(s):  
H. Q. Xiong ◽  
R. A. Wolff ◽  
K. R. Hess ◽  
G. R. Varadhachary ◽  
J. C. Blais ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Survival Duration ◽  
Second Line ◽  
Second Line Therapy ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
Measurable Disease ◽  
Ecog Ps

4119 Background: There is no established chemotherapy for patients with pancreatic cancer who have progressed on gemcitabine. This trial was designed to explore the efficacy of xelox as second line therapy in patients with pancreatic cancer. Methods: The primary objective was to determine overall survival at 6 months. It was estimated that 40 patients would be needed to detect 50% 6-month survival with 90% credible interval between 37%-62%. Eligibity criteria included biopsy-confirmed diagnosis of adenocarcinoma of the pancreas, one prior systemic chemotherapy, ECOG performance status (PS) 0–2, and adequate hepatic, renal, and bone marrow functions. Oxaliplatin was administered at 130 mg/m2 and capecitabine at 1000 mg/m2 twice daily for 14 days for patients who were younger than 65 and had ECOG PS score 0–1. For patients older than 65 or PS 2, the oxaliplatin dose was decreased to 110 mg/m2 and capecitabine to 750 mg/m2/twice daily. The treatment was repeated every 3 weeks. Tumor measurements were performed every 9 weeks (3 cycles) in patients who had measurable disease by RECIST criteria, although measurable disease was not required. Results: A total of 41 patients were enrolled into the study, 2 were never treated. Among 39 evaluable patients, 17 were female, median age 62 years (45–75), and 8 had ECOG PS 2. For the 36 patients who have completed therapy, the median number of treatment cycle was 3 (range, 1–6). Grade 3 or 4 toxicities included: abdominal pain (2 patients), dehydration (3), diarrhea (2), fatigue (6), gastrointestinal syndrome (including diarrhea and colitis) (4), hand-foot syndrome (1), hematemesis (1), mastitis (1), myocardial infarction (1), nausea/vomiting (2), neuropathy (1), non-neutropenic fever (1), pneumonia (1). One patient had a partial response and 8 others had stable disease. Median survival duration was 5.8 months (95% confidence interval [CI] 3.2–12.1 months). The six month and 1 year survival rate was 48% (95% CI 33%-70%) and 22% (95% CI 9%-51%), respectively. Conclusions: When used in the second line setting, the xelox has promising activity in pancreatic cancer. [Table: see text]

Tolerability and clinical outcomes in elderly patients with advanced pancreatic cancer treated with FOLFIRINOX.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 404-404 ◽  
Author(s):  
Taikan Yamamoto ◽  
Yu Sunakawa ◽  
Yutaro Kubota ◽  
Teppei Tagawa ◽  
Yasuhiro Kaga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
The Elderly ◽  
Elderly Group ◽  
Severe Neutropenia ◽  
Severe Toxicity ◽  
Ecog Performance Status ◽  
Significant Difference

404 Background: FOLFIRINOX, a combination chemotherapy of 5-FU, oxaliplatin, and irinotecan, has contributed to the overall survival (OS) benefit of advanced pancreatic cancer (PC), of which a major concern is severe toxicity such as neutropenia and diarrhea. Some elderly patients (pts) with PC need such an intensive chemotherapy in practical treatment; however, tolerability and efficacy for the regimen in the elderly are not well known. We report a retrospective analysis for toxicity and efficacy of FOLFIRINOX treatment in elderly pts with advanced PC. Methods: We analyzed pts with unresectable/metastatic PC, ECOG performance status 0 or 1, neutrocyte over 1500/mm3, and hemoglobin over 9g/dl, who received FOLFIRINOX as 1st- or 2nd-line therapy between November 2012 and July 2015 in 3 institutes of Showa University, Japan. All pts were divided into two groups, elderly group with pts 65 years of age or older and younger group with pts under 65 years old, then were compared in the toxicity and efficacy of FOLFIRINOX treatment. Results: Fifty-nine pts (median age: 62 years) were enrolled in this study: elderly and younger groups included 26 pts (median age: 70 years) and 33 pts (median age: 57 years), respectively. Severe neutropenia with grade 4 was numerically more frequent in the elderly group compared to the younger group (54% vs. 36%, p = 0.17). However, rate of febrile neutropenia was similar between the groups: 3 (12%) pts for the elderly group and 2 (6%) pts for the younger group. There was no difference in frequency of any grade toxicities, and no FOLFIRINOX treatment-related death was observed in both groups. Response rate was 14% (5/26) for the elderly group and 33% (11/33) for the younger group, with no significant difference (p = 0.22). Median progression-free survival (PFS) and OS were comparable between the elderly and younger groups (5.3 months vs. 5.4 months, log-rank p = 0.47 for PFS; not-reached vs. 10.7 months, long-rank p = 0.49 for OS). Conclusions: Our study suggests that FOLFIRINOX treatment is tolerable and active for the elderly pts with advanced PC, although frequency of severe neutropenia is higher in the elderly compared to the younger pts.

Olaparib (O) in patients (pts) with pancreatic cancer with BRCA1/2 inactivating mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4637-4637
Author(s):  
Eugene R Ahn ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Carmen Julia Calfa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Elevated Liver Enzymes ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Inactivating Mutations

4637 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pancreatic cancer pts with germline or somatic BRCA1/2 inactivating mutations treated with O are reported. Methods: Eligible pts had advanced pancreatic cancer, no standard treatment (tx) options available, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received O tablets or capsules dosed at 300 mg (n=27) or 400 mg (n=3), respectively, orally twice daily until disease progression. Simon 2-stage design tested the null disease control (DC) (objective response (OR) or stable disease at 16+ weeks (wks) (SD16+) according to RECIST) rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS), and safety. Results: Thirty pts with BRCA1/2 inactivating mutations were enrolled from Nov 2016 to Aug 2019; 20 were previously treated with platinum based therapy. Two were not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One partial response (PR) and 7 SD16+ were observed for DC and OR rates of 31% (90% CI: 18% - 40%) and 4% (95% CI: 0% - 18%), respectively. Seven pts had at least one grade 3 AE or SAE at least possibly related to O including anemia, diarrhea, fever, elevated liver enzymes, enterocolitis, increased bilirubin, and oral mucositis. Conclusions: Monotherapy O showed anti-tumor activity in heavily pre-treated pts with pancreatic cancer with germline (5/12 pts with OR or SD16+) or somatic (3/16 pts with OR or SD16+) BRCA1/2 inactivating mutations extending findings of recent studies of O in pts with advanced pancreatic cancer. Clinical trial information: NCT02693535 . [Table: see text]

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