Survival In Advanced Pancreatic Cancer Research Articles

Effect of Radiologically Evaluated Sarcopenia on Survival in Advanced Pancreatic Cancer

Effect of Radiologically Evaluated Sarcopenia on Survival in Advanced Pancreatic Cancer

Codon-specific KRAS mutations predict survival in advanced pancreatic cancer

Codon-specific KRAS mutations predict survival in advanced pancreatic cancer

Abstract A101: Codon-specific KRAS mutations predict survival in advanced pancreatic cancer

Abstract Background: How distinct KRAS alterations in pancreatic adenocarcinoma (PDAC) influence tumor initiation and outcomes remains unclear. Moreover, KRAS is now partly targetable with novel specific inhibitors targeting KRASG12 (G12C or G12D) but specific outcomes of these subgroups of patients is poorly described. We analyzed clinical/genomic characteristics, and outcomes of PDAC depending on codon-specific KRAS (G12 vs others), as well as gene expression profiles and in vitro drug sensibility using organoids (PDO). Methods: All metastatic patients with PDAC and available molecular profile from 2015-2022 were eligible and patients with KRAS mutation were included (NCT0493252) in a monocentric retrospective cohort. A cohort of PDO was used to assess the efficacy of 25 antitumor therapies (chemogram) and transcriptomic data from 69 KRAS-mutated tumors was also analyzed. Results: Overall, 263 patients were included, 238 KRASG12 (91%) and 24 (9%) KRASother. There was no difference between KRASG12 and KRASother regarding clinicopathological characteristics and potentially actionable alterations, except for BRAF that was found in 13% of KRASother (p=0.01). GNAS was found more altered in KRASother tumors (p=0.002) suggesting potential TIPMP precursors. Median overall survival from metastatic diagnosis was 16.7 months (95%CI:14.3-18.3) in KRASG12 and 24.9 months (95% CI:17.4-43.4) in KRASother (HR (ref:KRASG12)=0.56 (0.34-0.94), p=0.03 adjusted). First-line treatment-response was not different between groups (ORR and PFS), as confirmed with a similar PDO in vitro sensibility. Transcriptomic analyses showed a significant and exclusive upregulation of immune pathways in KRASG12 tumors. Conclusion: Codon-specific KRAS mutations are not equal and we report for the first time that KRASG12 patients have a worst prognosis than KRASother patients in PDAC. KRASG12 appears as a prognostic factor, as confirmed by transcriptomic analyses. These results warrant to be confirmed in larger scale studies. Citation Format: Alice Boilève, Adrien Rousseau, Marc Hilmi, Anthony Tarabay, Jacques R.R. Mathieu, Negaar Goudarzi, Jérôme Cartry, Sabrina Bedja, Claudio Nicotra, Maud NgoCamus, Valérie Boige, Marine Valéry, Mohamed Amine Bani, Lambros Tselikas, Antoine Italiano, Fanny Jaulin, Cristina Smolenschi, Antoine Hollebecque, Michel Ducreux. Codon-specific KRAS mutations predict survival in advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A101.

151P Relationship between depth of response and early tumor shrinkage with overall survival in advanced pancreatic cancer

151P Relationship between depth of response and early tumor shrinkage with overall survival in advanced pancreatic cancer

First-line chemotherapy regimens associated with survival in advanced pancreatic cancer: A Mexican single-center, real-world study.

683 Background: Effectiveness of FOLFIRINOX and Gemcitabine – Nabpaclitaxel as first-line chemotherapy regimens in advanced pancreatic cancer has been demonstrated in phase III clinical trials. However, prospective studies directly comparing both interventions are lacking. Gemcitabine has proved effective when combined with other drugs such as Oxaliplatin. Despite GEMOX has not proved overall survival benefit over Gemcitabine and it is unclear if its effectiveness could be similar to FOLFIRINOX or Gemcitabine-Nabpaclitaxel, it is broadly used as first line chemotherapy in our center due to safety concerns and higher costs associated to FOLFIRINOX and Nabpaclitaxel. Methods: We retrospectively analyzed data of patients with stage IV Pancreatic Adenocarcinoma treated at Instituto Nacional de Cancerología from 2014 to 2021. Our aim was to compare Overall Survival (OS) in patients treated with GEMOX, FOLFIRINOX, Gemcitabine-Nabpaclitaxel, or Gemcitabine in the front-line setting. Progression Free Survival (PFS), Overall Response Rate (ORR) and Adverse Effects (AEs) were also assessed. Results: A total of 141 patients were analyzed, 72 (51.0%) were treated with GEMOX, 13 (9.2%) with FOLFIRINOX, 9 (6.4%) with Gemcitabine-Nabpaclitaxel and 47 (33.3%) with Gemcitabine. Median Overall Survival for each regimen was: 11.0, 10.7, 6.7 and 4.7 months; (p = 0.078), and median PFS was 9.2, 6.5, 5.7 and 4.0 months, respectively (p = 0.026).ORR was 21.6%, 20.0%, 11.1%, 4.8% with GEMOX, FOLFIRINOX, Gemcitabine-Nabpaclitaxel and Gemcitabine, respectively. The percentage of patients who received a second line chemotherapy after progression was 43.1%, 61.5%, 55.6% and 23.4%, (p = 0.031). Regarding AEs, G3/4 most common effects ( > 5%) were Neutropenia (9.8%, 30.0%, 55.6%, 4.8%; p = 0.001), Diarrhea (2.0%, 10.0%, 11.1%, 0.0%; p = 0.247), and Increased Liver Enzymes (7.8%, 20.0%, 0.0%, 4.8%; p = 0.371). Grade 1/2 Neuropathy was found in 43.1%, 60.0%, 44.4% and 9.5%, p = 0.018. The percentage of patients who required GCSF was 9.8%, 60.0%, 22.2% and 9.5%, P = 0.001. Conclusions: In patients with advanced pancreatic cancer treated with different chemotherapy regimens, median OS was similar in this real-world analysis. Though PFS was higher in the group of patients treated with GEMOX, a higher percentage of patients initially treated with FOLFIRINOX or Gemcitabine – Nabpaclitaxel reached 2nd line chemotherapy after progression. Percentage G3/4 Neutropenia, G1/2 Neuropathy and use of GCSF were significantly higher in patients treated with FOLFIRINOX.

1309P CD8+ T cell infiltration is associated with improved survival in advanced pancreatic cancer

Pancreatic Ductal Adenocarcinoma (PDAC) is considered a cold tumour and immune checkpoint inhibitors have proved unsuccessful thus far. Despite this there is variability in the number of intratumoral CD8+ T cells across the malignant epithelium and the microenvironment (TME).

Impact of first-line FOLFIRINOX versus Gemcitabine/Nab-Paclitaxel chemotherapy on survival in advanced pancreatic cancer: Evidence from the prospective international multicentre PURPLE pancreatic cancer registry

BackgroundFirst-line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head phase III randomised controlled trials (RCT). Data on optimum first-line treatment and subsequent sequencing is lacking. ObjectiveTo compare overall survival (OS) between first-line treatment regimens in a real-world population to determine if an optimal therapeutic sequence is associated with survival benefit. MethodsA retrospective analysis of prospectively collated data from the Australasian PURPLE pancreatic cancer registry was undertaken. FindingsFrom 2016 to 2020, of 1551 pancreatic cancer patients, 615 received palliative-intent chemotherapy. Patients with early-stage resected disease without recurrence (n = 369), radiotherapy alone (n = 43), received supportive care alone (n = 458) or had less than 3 months follow-up (n = 66) were excluded. Median OS was comparable between patients receiving first-line Gemcitabine/Nab-Paclitaxel (n = 376) and those receiving FOLFIRINOX (n = 73) (11.3 versus 12.3 months, P = 0.37), with 38% proceeding to second-line chemotherapy which was associated with longer mOS compared to first-line treatment alone (17.4 versus 8.2 months, P < 0.001). With second-line treatment following prior FOLFIRINOX (n = 29) or Gemcitabine/Nab-Paclitaxel (n = 101), mOS did not differ significantly (17.3 versus 15.9 months, P = 0.92), respectively, whilst median progression-free survival was longer with prior FOLFIRINOX (5.2 versus 2.9 months, P = 0.03). ConclusionThere was no significant difference in overall survival between either first-line chemotherapy choice, despite patients receiving FOLFIRINOX being younger, fitter, and more likely to have localised disease. However, FOLFIRINOX was associated with delayed progression. In the absence of phase III RCT data, clinicians should be comfortable using either Gemcitabine/Nab-Paclitaxel or FOLFIRINOX as first-line therapy in advanced PDAC.

016 Testosterone Deficiency in Men being Treated for Primary Pancreatic Cancer

Few studies have investigated testosterone deficiency in non-prostate cancers. Previously, inflammation and opiod use has been associated with hypogonadism and shorter survival in advanced pancreatic cancer. Furthermore, a significant proportion of these patients note a lack of sexual interest or enjoyment in the small number of studies conducted on this topic. Despite many of these patients experiencing symptoms of testosterone deficiency such as fatigue, weakness, cognitive dysfunction, and decreased lean muscle mass, there exists sparce literature on testosterone testing patterns in practice and the prevalence of testosterone deficiency in this population.

Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients.

PurposeKras mutation and abnormal immune status are associated with pancreatic cancer development and progression. In this study, we evaluated the Kras mutation status in circulating tumor DNA and circulating T cell subsets in a cohort of advanced pancreatic cancer patients.MethodsSamples were retrospectively obtained from a series of 210 pathological advanced pancreatic cancer patients between 2012 and 2014. The Kras mutation status was detected in cell‐free circulating tumor DNA (ctDNA) by ddPCR and circulating T cell subsets were analyzed by flow cytometry.ResultsUnivariate analysis found that tumor node metastasis (TNM) stage, chemotherapy, circulating regulatory T cells, CA19‐9 levels, CA125 levels, and KrasG12D and KrasG12V mutations were significantly related to overall survival in advanced pancreatic cancer patients. Multivariate analysis identified that TNM stage (P = .03, HR:1.422), Tregs (P = .004, HR:1.522), CA19‐9 levels (P = .009, HR:1.488), KrasG12D mutation (P = .044, HR:1.353), and KrasG12V mutation (P = .001, HR:1.667) were independent prognostic markers. Furthermore, we found that KrasG12V mutation in ctDNA was correlated with high circulating proportion of Tregs, and patients with both KrasG12V mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer.ConclusionKrasG12V mutation was associated with high circulating regulatory T cell levels, and both of them predicted worse prognosis in advanced pancreatic cancer patients.

Are left ventricular muscle area and radiation attenuation associated with overall survival in advanced pancreatic cancer patients treated with chemotherapy?

To evaluate whether cardiac muscle area and radiation attenuation, determined using pre-chemotherapy computed tomography (CT), are associated with therapeutic response and overall survival (OS) in chemotherapy-treated advanced pancreatic cancer (APC) patients. Ninety-eight chemotherapy-treated APC patients who underwent pre-chemotherapy CT between 2009 and 2018 were considered. Left ventricular muscle area (LVMA) and left ventricular muscle radiation attenuation (LVMRA) were measured using pre-chemotherapy arterial-phase CT. OS and progression-free survival (PFS) were analysed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to analyse potential factors affecting OS and PFS. Patients with low LVMRA, low LVMA at baseline CT, and multiple metastases had a significantly shorter median OS than patients with high LVMRA, high LVMA, and without multiple metastases (8.8 versus 14 months, p=0.017; 12.2 versus 18.1 months, p=0.038; 7.3 versus 13.5 months, p<0.001, respectively). Patients with low LVMRA and distant metastasis had a shorter median PFS than patients with high LVMRA and those without distant metastasis (4.9 versus 8.3 months, p=0.032; 5.4 versus 9.9 months, p=0.002, respectively). Moreover, the mean LVMRA was the highest in the partial response group (p=0.028). LVMRA could well predict PFS and OS in chemotherapy-treated APC patients.

Abstract B16: CTC-based efficacy of SM-88 correlates with overall survival in advanced pancreatic cancer

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with 80% of patients succumbing within the first year and only 8% surviving &amp;gt;5 years. Responses are rare in later-line, metastatic PDAC trials. Thus, there is a clear unmet need to develop new treatment approaches guided by new and more accurate efficacy markers correlating with overall survival (OS) and not classical RECIST. SM-88 (racemetryrosine) used with methoxsalen, phenytoin, and sirolimus (MPS) has demonstrated effective reduction in circulating tumor cells (CTCs) in prostate and PDAC using multiple CTC assay variations. We now report OS associations. Method: Randomized phase II, multicenter, open-label prospective trial evaluating SM-88 in advanced PDAC. Ninety-nine patients were screened; 49 met inclusion criteria, with 38 evaluable per protocol. The trial evaluated overall survival, CTCs, PK parameters, and RECIST-determined response. Additional metabolism-related measures hypothesized to be impacted by SM-88s were also investigated (leptin, NLR, glucose, and others). CTCs were measured using a next-generation, microfluidic magnetic-based antibody detection method. Results: Preliminary results showed multiple efficacy measures correlated with overall survival. At baseline, in all evaluable patients (n=38, mean age 66yrs, approximately 80% having &amp;gt;2 prior lines) median CTCs were 110.8 CTCs/4mL, whereas those who achieved stable disease (SD) (n=4) and whose CTC levels decreased on SM-88 reported 123.2 CTCs/4mL at baseline. However, one patient who was a CTC responder and achieved a partial response (PR) had 13.3 CTCs/4mL at baseline. Patients with both an absolute and percent decrease from baseline in CTCs demonstrated greater OS using multiple threshold reductions; patients with &amp;gt;80% decrease or reduction in cell count to &amp;lt;50 CTCs/4mL demonstrated the strongest correlation with extended survival (p=0.18). Higher SM-88 Cmax (p=0.07) and AUC-6 (p&amp;lt;0.001) also correlated with OS. Based on RECIST, the clinical benefit rate (stable disease [SD] plus partial response [PR]) was 44%. There was a demonstrated survival advantage for patients who achieved SD (p&amp;lt;0.02). Females also achieved greater OS (p=0.01), which suggests the need for further clinical investigation. Metabolic measures of glucose levels (p=0.46) and leptin (p=0.28) did not appear to differ by sex. Conclusion: These data for SM-88 in PDAC illustrate that there are clear efficacy correlates with overall survival beyond traditional RECIST responses, including CTC measures. This may be of translational significance as the association between decreases in CTCs and overall survival had not been previously well documented prospectively in PDAC as compared to other tumor types. All together, these data are encouraging and warrant additional clinical investigation aimed at improving the dismal outcome of this malignancy. Citation Format: Marcus Smith Noel, Andrea Wang-Gillam, Allyson J. Ocean, Sant Chawla, Vincent Chung, Ron Korn, Giuseppe Del Priore, Vincent J. Picozzi. CTC-based efficacy of SM-88 correlates with overall survival in advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B16.

Neoantigen-reactive T cells combined with chemotherapy and radiation improved survival in advanced pancreatic cancer

Neoantigen-reactive T cells combined with chemotherapy and radiation improved survival in advanced pancreatic cancer

Effect of neoantigen reactive T cells combined with chemotherapy and radiation on survival in advanced pancreatic cancer.

e15756 Background: Pancreatic cancer (PC) is one of the most aggressive and death-relating malignancy. Gemcitabine (GEM) is the key agent in the first-line standard regimen for advanced PC, which is mostly diagnosed at advanced stage and unsuitable for curative resection. The objective responsive rate (ORR) and medium progression free survival (PFS) of various GEM-based regimens are still unsatisfied. Therefore, development of new therapeutic modalities, including immunotherapy, is needed. This study is to investigate the efficacy, safety and clinical beneficial of combination neoantigen based immunotherapy with GEM and radiotherapy in locally advanced and metastatic PC patients. Methods: Three locally advanced unresectable and seven metastatic PC patients received at least two cycles of GEM (1000mg/m2 on day 1 and day 6), radiotherapy combing with neoantigen induced DC vaccination on day 7 and cytotoxic T lymphocyte transfer from day 12 to 15 (repeated every 21 days). The locally advanced unresectable PC patients received stereotactic body radiotherapy (SBRT) with a total amount of 50-66Gy during the first cycle. For metastatic patients, their partial lesions received a low dose radiation (0.5Gy bid*2days ) on day 10 and 11 in each cycle. Results: Two cases were observed with partial remission (PR), five with stable disease (sd), and three with progressive disease (PD). The disease control rate (DCR) was 70%. Median progression free survival (PFS) was 6.4 months. After the first treatment cycle, the total effectiveness for pain easement and increasing appetite are 100% (8/8)and 66.7%, respectively. Haematotoxicities with a 40% incidence rate were the most common adverse drug reactions. Two patients had grade 1 to 2 neutropenia, two with grade 3 to 4 thrombocytopenia. Three patients suffered grade 1 to 2 gemcitabine-induced skin rash. No treatment-related mortality occurred. Conclusions: Neoantigen reactive T cells combined chemoradiotherapy demonstrated an acceptable response and safety in advanced pancreatic cancer patients.

Modified FOLFIRINOX for unresectable locally advanced/metastatic pancreatic cancer. A real-world comparison of an attenuated with a full dose in a single center experience.

Purpose: Metastatic pancreatic adenocarcinoma has a very poor prognosis. Although irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) significantly increases survival in advanced pancreatic cancer, compared to employing only gemcitabine (GEM), toxicities have tempered enthusiasm for its use.Methods: This study retrospectively analyses the real-world clinical practice with full and attenuated doses of FOLFIRINOX in unselected patients with locally advanced unresectable or metastatic pancreatic cancer, treated at an Italian general hospital. Efficacy, tolerability, and toxicity were evaluated, and overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan–Meier method.Results: Fifty consecutive patients with advanced (13) or metastatic (37) pancreatic adenocarcinomas were treated with FOLFIRINOX at the Medical Oncology Unit, Piacenza General Hospital, North Italy. The first enrolled consecutive 18 patients (36%) of this series started the treatment with a full dose of the regimen, while the subsequent 32 (64%) consecutive patients received dose attenuation (−20% bolus fluorouracil and −25% irinotecan). In the entire group, the response rate, median OS, and median PFS were 30%, 10.1 months, and 5.6 months, respectively, with no differences in objective response in the 32 patients that received an attenuated dose compared with the 18 patients receiving a full dose of chemotherapy. However, neutropenia, anemia, fatigue, and vomiting were statistically increased in the 18 patients receiving a full dose compared with the 32 patients receiving an attenuated dose of FOLFIRINOX (p<0.05).Conclusion: This study demonstrates the efficacy and tolerability of modified FOLFIRINOX in advanced and metastatic pancreatic cancer.

Prognostic values of abdominal body compositions on survival in advanced pancreatic cancer.

To investigate the clinical impact of body composition on outcomes in advanced pancreatic cancer (APC), we performed a retrospective analysis of patients diagnosed with APC between 2010 and 2016. The extent of visceral fat, subcutaneous fat, and skeletal muscle was measured using computed tomography (CT) images, together with visceral to subcutaneous adipose tissue area ratio (VSR) and skeletal muscle index (SMI). The effects of these body composition parameters on survival in APC were explored. In total 203 APC patients were enrolled in this study, with a median age of 65 years (range: 31–80 years). The median overall survival (OS) was 9.5 months (95% confidence interval, 7.6–12.4 months). The survival analysis showed that OS in patients with high SMI was significantly longer than those in patients with low SMI (11.1 vs 8.0 months, P < .001). However, when analyzed with VSR, the OS in patients with high VSR was significantly shorter than those in patients with low VSR (8.3 vs 9.4 months, P < .001). Multivariate analyses revealed that ECOG performance status (hazard ratio [HR]: 1.56; P < .001), stage III (HR: 0.63; P = .039), SMI (HR: 0.92; P = .019), VSR (HR: 1.38; P = .005), and skeletal muscle area (HR: 0.95; P = .049) were independent risk factors for mortality. In conclusion, visceral adiposity, as well as low muscle mass and quality, was closely associated with OS of APC. Therefore, evaluating body compositions may be a practical approach for predicting patient prognosis.

P-186 - Chemotherapy for patients with advanced or metastatic pancreatic cancer (AMPC)

Introduction: Pancreatic cancer is a common, highly lethal disease that is rising in incidence. Chemotherapy based on 5-fluorouracil (5-FU) has been shown to prolong survival in advanced pancreatic cancer. Gemcitabine improves major symptoms and survival outcomes compared with bolus 5-FU. Many novel small molecules are being widely and actively researched. These compounds are based on classical mechanisms of action as well as biological therapies targeting novel cellular survival pathways. Methods: The primary objective of this retrospective analysis is to evaluate overall survival; the secondary objective is to evaluate progression-free survival and toxicity of gemcitabine-cisplatin in AMPC after 4 cycles. Inclusion criteria were histologically proven pancreatic carcinoma, no prior chemotherapy (adjuvant chemotherapy allowed if more than 6 month before), no other serious concomitant illness ECOG PS < 2, adequate renal and liver function, good marrow reserve. Results: From 01/2010 to 12/2015, 90 patients were enrolled in this study. Median age 57.8 ± 1.5 years old (21-80), with a total 410 cycles were administrated, median = 4 (4- 8). All patients were evaluated for efficacy and toxicity. Median of overall survival was 7.1 months[3-17 months]; median of progression free survival was 3.4 months, the overall response rate was 10% and disease control rate was 32% including 10% partial response, 22% had stable disease. Grade ¾ toxicities evaluated were asthenia 3%, leucopenia 1%, neutropenia 2%, anemia 1.5%, vomiting 1.5%, thrombopenia 1%, mucositis 1%. Conclusion: Gemcitabine-cisplatin is moderately effective and well tolerated as first line treatment for AMPC with a correct quality of life. The results of chemotherapy in metastatic or advanced pancreatic cancer remain poor; they must be improved by other therapeutic combinations.

Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer

Background:Mutations in the KRAS gene can be detected in about 70–90% of pancreatic cancer (PC) cases. Whether these mutations have a prognostic or predictive value remains elusive. Furthermore, the clinical relevance of the extended RAS (KRAS+NRAS) mutational status is unclear in PC.Methods:We prospectively defined a PC patient population who received erlotinib-free chemotherapy regimens. A statistically significant difference between KRAS wild-type and KRAS mutated tumours in at least 160 patients in this population would support the assumption of a rather prognostic role of KRAS.Results:One hundred and seventy-eight tumour samples were collected from prospective clinical studies and successfully analysed for the extended RAS status: 37 tumours were KRAS wild-type (21%), whereas 141 (79%) carried a KRAS mutation; 132 of these mutations were found in KRAS exon 2 (74%), whereas only 9 mutations (5%) were detected in KRAS exon 3. Within KRAS exon 4 and NRAS exons 2–4, no mutations were apparent. There was no significant difference in overall survival for KRAS wild-type vs mutant patients (9.9 vs 8.3 months, P=0.70).Conclusions:Together with the results of the AIO-PK-0104-trial, the present analysis supports the notion that KRAS mutation status is rather predictive than prognostic in advanced PC.

Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial

Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer. The Vandetanib in Pancreatic Cancer (ViP) trial was a phase 2 double-blind, multicentre, randomised placebo-controlled trial in previously untreated adult patients (aged ≥18 years) diagnosed with locally advanced or metastatic carcinoma of the pancreas confirmed by cytology or histology. Patients had to have an Eastern Cooperative Oncology Group (ECOG) score of 0-2 and a documented life expectancy of at least 3 months. Patients were randomly assigned 1:1 to receive vandetanib plus gemcitabine (vandetanib group) or placebo plus gemcitabine (placebo group) according to pre-generated sequences produced on the principle of randomly permuted blocks with variable block sizes of two and four. Patients were stratified at randomisation by disease stage and ECOG performance status. All patients received gemcitabine 1000 mg/m2 as a 30-min intravenous infusion, weekly, for 7 weeks followed by a 1-week break, followed by a cycle of 3 weeks of treatment with a 1-week break, until disease progression, and either oral vandetanib 300 mg per day once daily or matching placebo. Patients and investigators were masked to treatment assignment. The primary outcome measure was overall survival (defined as the difference in time between randomisation and death from any cause or the censor date) in the intention-to-treat population. This trial has been completed and the final results are reported. The study is registered at EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. Patients were screened and enrolled between Oct 24, 2011, and Oct 7, 2013. Of 381 patients screened, 142 eligible patients were randomly assigned to treatment (72 to the vandetanib group and 70 to the placebo group). At database lock on July 15, 2015, at a median follow-up of 24·9 months (IQR 24·3 to not attainable), 131 patients had died: 70 (97%) of 72 in the vandetanib group and 61 (87%) of 70 in the placebo group. The median overall survival was 8·83 months (95% CI 7·11-11·58) in the vandetanib group and 8·95 months (6·55-11·74) in the placebo group (hazard ratio 1·21, 80·8% CI 0·95-1·53; log rank χ21df 1·1, p=0·303). The most common grade 3-4 adverse events were neutropenia (35 [49%] of 72 patients in the vandetanib group vs 22 [31%] of 70 in the placebo group), thrombocytopenia (20 [28%] vs 16 [23%]), hypertension (nine [13%] vs 11 [16%]), leucopenia (12 [17%] vs 13 [19%]), and fatigue (17 [24%] vs 15 [21%]). No treatment-related deaths occurred during the study. The addition of vandetanib to gemcitabine monotherapy did not improve overall survival in advanced pancreatic cancer. Tyrosine kinase inhibitors might still have potential in the treatment of pancreatic cancer but further development requires the identification of biomarkers to specifically identify responsive cancer subtypes. Cancer Research UK and AstraZeneca.

Autologous cytokine-induced killer cell transfusion increases overall survival in advanced pancreatic cancer.

BackgroundAdvanced pancreatic cancer (PC) has very poor prognosis with present treatments, thus necessitating continued efforts to find improved therapeutic approaches. Both preclinical and preliminary clinical data indicate that cytokine-induced killer (CIK) cells are an effective tool against various types of solid tumors. Here, we conducted a study to determine whether CIK cell-based therapy (CBT) can improve the outcomes of advanced PC.MethodsEighty-two patients with advanced PC, whose predicted survival time was longer than 3 months, were analyzed retrospectively. Of all the patients, 57 individuals were receiving chemotherapy, while the remaining 25 individuals were treated with CBT.ResultsThe overall survival analysis was based on 48 deaths in the 57 patients in the chemotherapy group (84.2 %) and 18 deaths in the 25 patients in the CBT group (72.0 %). In the CBT group, the median overall survival time was 13.5 months, as compared to 6.6 months in the chemotherapy group (hazard ratio for death, 0.39; 95 % confidence interval, 0.23 to 0.65; p < 0.001). The survival rate was 88.9 % in the CBT group versus 54.2 % in the chemotherapy group at 6 months, 61.1 % versus 12.5 % at 12 months, and 38.9 % versus 4.2 % at 18 months. The disease control rate was 68.0 % in the CBT group and 29.8 % in the chemotherapy group (p < 0.001).ConclusionsThese results from this retrospective analysis appeared to imply that CBT might prolong survival in these high-risk PC patients. Prospective study is needed to corroborate this observation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0237-6) contains supplementary material, which is available to authorized users.

Progression-free survival as a surrogate endpoint for overall survival in advanced pancreatic cancer: A meta-analysis

Progression-free survival as a surrogate endpoint for overall survival in advanced pancreatic cancer: A meta-analysis