Predictive role of FAS for trabectedin in second lines of advanced soft tissue sarcoma (ASTS): A Spanish group for research on sarcoma (GEIS) study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11071-11071 ◽  
Author(s):  
Javier Martin Broto ◽  
David Marcilla ◽  
Rafael Ramos ◽  
David Silva Moura ◽  
Ramiro Alvarez ◽  
...  
Keyword(s):  
Selection Criteria ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Rank Test ◽  
Second Line ◽  
Kaplan Meier ◽  
Diagnostic Time ◽  
Predictive Role ◽  
Set Up

11071 Background: There are currently several second-line options for the treatment of ASTS as gemcitabine combinations, trabectedin, pazopanib, eribulin or olaratumab plus doxorubicin in cases where anthracyclins are still possible. There is an unmet need for predictive biomarkers which hinders the rational selection of the best sequence in second line. We already published the prognostic value of FAS in first line of ASTS while this study analyzes its predictive role in different second line schemes. Methods: Most relevant selection criteria for this study were having received trabectedin in 2nd line or beyond for ASTS, progressive disease after at least one previous line for ASTS and signed CI. A TMA was set up for FAS staining (Cell Signaling) with blocks from diagnostic time. Two expert blinded pathologists reviewed and classified the cases as negative, weak or strong. Kaplan–Meier estimations were used for time-to-event variables and the log-rank test was used to compare groups. Results: A series of 198 patients accomplished selection criteria. Metastases at diagnosis occurred in 46 (24%) and median time to metastases was 18.8 months (CI 16,3; 21.3). Previous line to trabectedin consisted of gemcitabine combination 83 (42%), Doxorubicin-based 65 (33%) and others 50 (25%). Median PFS for previous and trabectedin lines were 3.5 (2.8-4.2) and 3.4 (2.8-4) months respectively. FAS positive entailed significantly better PFS for the previous trabectedin line: 4.1 (1.5-6.7) vs 3.0 (2.5-3.5) months, p = 0.01 whereas FAS positive was related with worse PFS for the trabectedin line 2.5 (2.2-2.8) vs 3.7 (2.7-4.8) months, p = 0.028. These results were more notorious for L-sarcoma cases: 7.0 (3.6-10.5) vs 4.3 (1.9-6.6) months, p = 0.017 in previous line and 2.4 (2.2-2.6) vs 6.5 (3.8-9.3) months, p < 0.001 in trabectedin. From trabectedin administration, FAS+ had significantly worse OS especially in L-sarcomas: 11.9 (5.2-18.7) vs 21.7 (12.7-30.8) months, p = 0.002. Conclusions: FAS showed predictive value in PFS and OS for trabectedin administration in ASTS. The different prognostic role of FAS across distinct lines and its relevance in L-sarcomas deserve further attention.

scholarly journals Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034393 ◽  
Author(s):  
Alberto Bongiovanni ◽  
Chiara Liverani ◽  
Sara Pusceddu ◽  
Silvana Leo ◽  
Giovanni Di Meglio ◽  
...  
Keyword(s):  
Phase Ii Trial ◽  
Locally Advanced ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Pet Ct ◽  
Predictive Role ◽  
Grade 3 ◽  
Neuroendocrine Carcinomas

IntroductionPatients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accurate biomarkers are needed to facilitate diagnosis and prognostic assessment of patients with NEC.Methods and analysisThe SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. Secondary aims are to correlate the serum miRNA profile and primary mutational status of MEN1, DAXX, ATRX and RB-1 with prognosis and outcome and to investigate the prognostic and predictive role of the Ki-67 score and 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) or 68Ga-PET/CT. The main eligibility criteria are age ≥18 years; metastatic or locally advanced, non-resectable, grade 3 lung or GEP-NECs; progression to first-line platinum-based chemotherapy. A Bryant and Day design taking into account treatment activity and toxicity was used to estimate the sample size. All analyses will be performed separately for each treatment group in the intention-to-treat population. A total of 112 patients (56/arm) will be randomly assigned (1:1) to receive FOLFIRI every 14 days or CAPTEM every 28 days until disease progression or unacceptable toxicity or for a maximum of 6 months. Patients undergo testing for specific biomarkers in primary tumour tissue and for miRNA in blood samples. MiRNA profiling will be performed in the first 20 patients who agree to participate in the biological substudy.Ethics and disseminationThe SENECA trial, supported by Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), was authorised by the locals Ethics Committee and the Italian Medicines Agency (AIFA). Results will be widely disseminated via peer-reviewed manuscripts, conference presentations and reports to relevant authorities.The study is currently open in Italy.Trail registration numberNCT03387592; Pre-results. EudraCT-2016-000767-17.Protocol versionClinical Study Protocol Version 1, 7 November 2016.

scholarly journals From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2105
Author(s):  
Giulia Accordino ◽  
Sara Lettieri ◽  
Chandra Bortolotto ◽  
Silvia Benvenuti ◽  
Anna Gallotti ◽  
...  
Keyword(s):  
Unmet Need ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Integrated Approach ◽  
Point Of View ◽  
Novel Therapies ◽  
Car T ◽  
Treatment Data ◽  
Multidisciplinary Perspective

Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing a tailored treatment. Data from large studies investigating the role of immunotherapy in gastrointestinal cancers are promising but further investigations are necessary to better select those patients who can mostly benefit from these novel therapies. This review will focus on the treatment of metastatic esophageal and gastric cancer. We will review the standard of care and the role of novel therapies such as immunotherapies and CAR-T. Moreover, we will focus on the analysis of potential predictive biomarkers such as Modify as: Microsatellite Instability (MSI) and PD-L1, which may lead to treatment personalization and improved treatment outcomes. A multidisciplinary point of view is mandatory to generate an integrated approach to properly exploit these novel antiproliferative agents.

Consolidative Radioimmunotherapy after Chemoimmunotherapy in Patients with Histologic Transformation of Indolent Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1746-1746
Author(s):  
Patrick M. Reagan ◽  
Jennifer L. Kelly ◽  
Andrea Baran ◽  
Paul M. Barr ◽  
Carla Casulo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Unmet Need ◽  
Common Adverse Event ◽  
Secondary Outcome ◽  
Rank Test ◽  
Cell Transplant ◽  
Indolent Lymphoma ◽  
Mortality And Morbidity ◽  
Entire Cohort ◽  
Kaplan Meier

Abstract Introduction:Histologic transformation (HT) has been well characterized in follicular lymphoma (FL), and has historically carried a poor prognosis with median overall survival (OS) of 1.2-1.8 years (yrs) in the pre-rituximab era (Montoto et al, 2007; Al-Tourah et al 2008). Despite improved outcomes in the rituximab era (Link et al, 2013), HT still represents a major source of mortality and morbidity in these patients (pts). While there is emerging evidence that autologous stem cell transplant (ASCT) confers a survival advantage compared to chemotherapy with rituximab alone (Ban-Hoefen et al, 2013; Villa et al, 2013), many of these patients have contraindications such as advanced age and frailty precluding ASCT as an option. We report a strategy of radioimmunotherapy (RIT) consolidation after chemoimmunotherapy to address this unmet need. Methods: Consecutive pts ≥ 18 yrs old, who received RIT as consolidation after chemoimmunotherapy for HT at the Wilmot Cancer Institute were identified who had been deemed ineligible for ASCT. Inclusion criteria were as follows: 1) clinical, composite or pathologic diagnosis of HT, and 2) receipt of RIT after response to rituximab and chemotherapy. HT was defined as biopsy confirmed diffuse large B cell or Burkitt-like lymphoma by the WHO classification ≥6 months following a biopsy establishing indolent lymphoma diagnosis (pathologic HT), or clinical evidence of transformation as defined in previous cohorts (Al-Tourah et al, 2008; Link et al, 2013) in the absence of biopsy confirmation (clinical HT). Composite diagnosis of HT was defined as concurrent indolent and large cell lymphoma. The primary endpoint was overall survival (OS). Progression free survival (PFS) was a secondary outcome. Kaplan-Meier survival estimation curves were generated using SAS (SAS Institute Inc., Cary, NC, USA), and p values were generated using the log rank test. Results: 21 consecutive pts who had a clinical, composite, or pathologic HT diagnosis were included in this analysis. All of these pts responded to rituximab and chemotherapy (CHOP like n=18, other n=3), and were treated with RIT for consolidation. The median age at the time of HT was 66 yrs (44-90). Nine pts received I-131 tositumomab and 12 received Y-90 ibritumomab tiuxetan. The median OS from HT was 6.9 yrs in the entire cohort with a median follow up of 3.5 yrs (Figure). There were no statistical differences in outcomes between the pathologic (n=11) and clinical/composite (n=10) HT pts (p=0.33). There was also no difference between those who received rituximab prior to HT (n=13), and those who did not (n=8; p=0.88). Twelve pts experienced grade 3-4 thrombocytopenia, which was the most common adverse event (AE). Nine deaths occurred. Disease-related death was the most common cause (n=4), followed by death unrelated to disease or treatment (n=3) and treatment-related death (n=2). Figure: Kaplan-Meier estimate of OS after HT in pts receiving RIT after chemoimmunotherapy (n=21) Figure:. Kaplan-Meier estimate of OS after HT in pts receiving RIT after chemoimmunotherapy (n=21) Conclusions: We report the use of RIT as consolidation of response to chemoimmunotherapy in pts with HT. This represents one of the largest series focused on pts with HT who were deemed unfit for ASCT. The RIT was well tolerated in this analysis with only 2 treatment related deaths, one of which was secondary to therapy related acute myeloid leukemia. Our observed median OS compares favorably to published reports of pts with HT who are younger and able to tolerate more aggressive therapeutic options. Consolidative RIT should be considered as a treatment approach in this vulnerable population of pts, and can serve as a platform for the incorporation of novel agents into prospective clinical trials. Disclosures Barr: Pharmacyclics: Research Funding.

The predictive role of CA 19–9 kinetics for time-to-progression (TTP) and overall survival (OS) in patients receiving palliative first-line chemotherapy for advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15637-e15637
Author(s):  
M. Haas ◽  
S. Boeck ◽  
P. Stieber ◽  
R. P. Laubender ◽  
H. Buchner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
First Line ◽  
Predictive Role ◽  
Pre Treatment ◽  
Line Chemotherapy

e15637 Background: Previous studies showed contradictory results for a predictive role of CA 19–9 kinetics during chemotherapy in patients (pts) with pancreatic cancer (PC). Methods: We performed a retrospective, multicenter study in order to evaluate the role of CA 19–9 as a biomarker for TTP and OS in PC. Main inclusion criteria: histological confirmed diagnosis of PC, treatment with first-line chemotherapy for advanced disease, pre-treatment CA 19–9 level of > 5.2 U/ml. As CA 19–9 measurements were conducted in different laboratories using different commercial assays, we defined a subgroup of pts where CA 19–9 was assessed exclusively by the Elecsys assay (Roche Diagnostics). For the analysis of CA 19–9 kinetics, at least one follow-up measurement between day 20 and 64 during first-line chemotherapy had to be available. Pts were divided into two subgroups of CA 19–9 responders and non-responders by cut-offs of a 25% and 50% decline, respectively. OS and TTP were estimated with the Kaplan-Meier-Method, differences between the subgroups were analyzed by using the log-rank test. Results: One hundred and eighty-six pts were included, 83 of them were tested with the Elecsys method. Median age was 63 years, 90 % of the pts were treated within prospective clinical trials. Median pre-treatment CA 19–9 was 1076 U/ml (range 5.7–100,000 U/ml), the median bilirubin was 0.6 mg/dl. Median OS and TTP were 9.8 months (mo) and 5.4 mo, respectively. In univariate analysis, pts with a CA 19–9 decline of at least 25% during chemotherapy lived significantly longer (11.9 mo vs. 8.2 mo, p=0.003) and had a significantly prolonged TTP (5.8 mo vs. 4.4 mo, p=0.018) than those with a lower decline or even CA 19–9 increase. Data for the Elecsys-measurements were comparable (OS: 13.4 mo vs. 8.6 mo, p=0.004; TTP: 7.0 mo vs. 2.6 mo, p=0.003). None of the analyses demanding a CA 19–9 drop of at least 50% reached the level of statistical significance. Conclusion: An early CA 19–9 decline of 25% during first-line chemotherapy may predict OS and TTP in pts with advanced PC. Innovative statistical methods are required to improve our understanding of the utility of CA 19–9 as a predictive biomarker in PC. [Table: see text]

The role of serum carcinoembryonic antigen in predicting objective responses to chemotherapy and overall survival in patients with non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18084-e18084
Author(s):  
Hongbing Liu
Keyword(s):  
Protective Factor ◽  
Cox Regression ◽  
Rank Test ◽  
Small Cell Lung ◽  
Baseline Serum ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Serum Cea ◽  
Nsclc Patients

e18084 Background: Previous studies indicated the carcinoembryonic antigen (CEA) could predict the therapeutic objective response (OR) and overall survival (OS) of patients with cancers, including non-small cell lung cancer (NSCLC). However, the role it could play in evaluating therapeutic responses and OS in patients with NSCLC requires further elucidation. Herein, we investigated the potential role of CEA in predicting OR and OS in patients with NSCLC. Methods: 689 patients with NSCLC were enrolled between January 2000 and August 2011. The correlations between the CEA levels and OR or OS were examined via statistical analyses including the chi-squared test, logistical regression, paired-samples t-test, receiver operator characteristic curve, Kaplan-Meier survival analysis, log-rank test and Cox regression model. Results: The calculated cut-off for predicting an OR to chemotherapy in patients with NSCLC was a reduction of 5.28% in serum CEA. This value demonstrated a sensitivity of 61.3% and a specificity of 62.4%. Serum CEA levels significantly decreased after two cycles of chemotherapy in NSCLC patients (t = 2.196, P = 0.031). The Kaplan-Meier survival analysis indicated no significant correlation between baseline CEA and OS (log rank test =0.079). However, according to the Cox regression analysis the number of distant metastatic organs (=1 and ≥2) was the independent risk factor of the OS (P = 0.026; P =0.003), and the cycle numbers of chemotherapy was the protective factor for OS in patients with NSCLC (P=0.011).More importantly, baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes (P = 0.014; P = 0.017, respectively). Conclusions: Our study shows that baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes. While the baseline level of serum CEA was not a prognostic factor, the post-treatment reduction of serum CEA level can predict the OR in patients with NSCLC,. The number of chemotherapy cycles was the independent protective factor, while the numbers of distant metastatic organs was the independent risk factor for NSCLC patients’ OS.

Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 556-556 ◽  
Author(s):  
Takeru Wakatsuki ◽  
Eiji Shinozaki ◽  
Mitsukuni Suenaga ◽  
Izuma Nakayama ◽  
Tomohiro Matsushima ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adverse Events ◽  
Univariate Analysis ◽  
Rank Test ◽  
Multikinase Inhibitor ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Almost All ◽  
Therapy Target

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.

Three fluoropyrimidine-based regimens in second-line therapy following nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer: Efficacy and tolerance in clinical practice.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 370-370
Author(s):  
Anne Laure Pointet ◽  
David Tougeron ◽  
Simon Pernot ◽  
Astrid Pozet ◽  
Dominique Bechade ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Statistical Significance ◽  
Performance Status ◽  
Locally Advanced ◽  
Rank Test ◽  
Line Treatment ◽  
Second Line ◽  
Secondary Resection ◽  
Kaplan Meier ◽  
Metastatic Sites

370 Background: Combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a valid first-line treatment (1L) in metastatic pancreatic adenocarcinoma (MPA) in patients (pts) with performance status (PS) of 0,1 or 2, but there is currently no standard second-line treatment (2L) after this new 1L option. We evaluated survival outcomes and tolerability of three usual fluoropyrimidine-based regimens: FOLFOX, FOLFIRI or FOLFIRI.3 (FOLFIRI1/3), and FOLFIRINOX after N+G failure in MPA pts. Methods: We prospectively identified 138 pts from 11 French centers who received 1L N+G for unresectable pancreatic adenocarcinoma. After disease progression or unacceptable toxicity, we excluded pts with locally advanced cancer, or who underwent secondary resection/chemoradiotherapy. Three subgroups of 2L chemotherapy were identified: FOLFOX, FOLFIRI1/3 and FOLFIRINOX regimens. Response was evaluated by RECIST criteria, progression-free survivals (PFS1, PFS2), and overall survival (OS1, OS2) were calculated using Kaplan-Meier method and compared with the Log-rank test. Results: 61 pts with MPA received a 2L. Persistent neuropathy was present in 27% of pts. Median age was 71.7 years [41-83]. PS was 0, 1 or 2. Median 1L duration, number of metastatic sites, PS, CA19.9, albumin, and bilirubin levels, and persistent neuropathy grade were statistically comparable between the 3 subgroups. Median OS for all 2L pts was 6.0 months [4-8]. Third line regimen was used in 32.8% of 2L pts without statistical significance between the subgroups. Main grade 3/4 adverse events reported were thrombocytopenia (18%), anemia (7.7%), neutropenia (21.4%) and nausea (5.4%). No toxic deaths occurred. Conclusions: This study suggests a clinical benefit and a manageable toxicity profile of 2L fluoropyrimidine-based regimens after N+G failure in patients with MPA, in particularly combined with irinotecan.[Table: see text]

Clinical prognostic factors in patients with recurrent or metastatic carcinoma of the head and neck treated with immune checkpoints therapies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17530-e17530
Author(s):  
Carlo Resteghini ◽  
Stefano Cavalieri ◽  
Alessandro Rametta ◽  
Salvatore Alfieri ◽  
Donata Galbiati ◽  
...  
Keyword(s):  
Weight Loss ◽  
Head And Neck ◽  
Prognostic Value ◽  
Performance Status ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Biological Data ◽  
Smoking History ◽  
Immune Checkpoints ◽  
Rank Test

e17530 Background: Immunotherapy (IT) provides advantages in a small proportion of recurrent / metastatic head and neck squamous cell carcinoma (RM HNSCC) patients (pts). Predictive biomarkers are still an unmet need. We aimed to determine if known prognostic clinical factors in RM HNSCC as well as new variables hold prognostic value in the IT era. Methods: We conducted a retrospective analysis of a cohort of 106 RM HNSCC pts enrolled into IT trials at National Cancer Institute of Milan-Italy between Oct 2014 - Jul 2018. Using Log Rank test and Cox proportional hazard model we computed univariate and multivariate analysis (UVA; MVA) of demographics, clinical and biological data to assess their prognostic value for progression free survival (PFS) and overall survival (OS). Results: Ninety-three pts (M 75; F: 18) were included in the final analysis with a median follow up of 20.8 months. The majority (96%) were treated in platinum-refractory setting. Approximately half of pts received anti-PD-1 or anti-PDL-1 monotherapy while the remaining 52% received them in combination with other IT agents. Median OS and PFS were 6.5 (CI 95%: 4.6-10.4) and 2.1 months (CI 95%: 1.8-2.2), respectively. Statistically significant factors at UVA for PFS were smoking history - both pos vs neg and < vs ≥ 30 PY, disease subsite, weight loss > 5%, Karnosfky performance status (PSK), occurrence of any and G3-G4 drug related (DR) toxicities, neutrophil to lymphocytes ratio (NLR). Without stratification for disease subsite, MVA showed independent predictive value of prolonged PFS for positive smoking history (HR 0.5, p 0.02) and any DR toxicities (HR 0.43, p < 0.01). Several factors reached significance for OS in UVA (smoking history and PY, weight loss > 5%, ECOG PS, PSK, occurrence of any toxicities, CRP, baseline C-reactive protein, antibiotic use, steroid use in the 30 days before IT). Of these, PSK (HR 0.95, p 0.01) and any DR toxicities (HR 0.3, p < 0.01) resulted to be predictive in the MVA. Conclusions: Clinical parameters, especially pretreatment PSK, smoking history and occurrence of any DR toxicities, appear to be strong predictors of outcome in RM HNSCC pts treated with IT. These results should be validated in an independent cohort.

scholarly journals Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

2021 ◽  
Vol 11 ◽  
Author(s):  
Eleonora Lai ◽  
Stefano Cascinu ◽  
Mario Scartozzi
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Vascular Endothelial ◽  
The Novel ◽  
Second Line ◽  
Endothelial Growth Factor

Targeting tumor-driven angiogenesis is an effective strategy in the management of metastatic colorectal cancer (mCRC); however, the choice of second-line therapy is complicated by the availability of several drugs, the occurrence of resistance and the lack of validated prognostic and predictive biomarkers. This review examines the use of angiogenesis-targeted therapies for the second-line management of mCRC patients. Mechanisms of resistance and anti-placental growth factor agents are discussed, and the role of aflibercept, a recombinant fusion protein consisting of portions of human vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, is highlighted. The novel mechanism of action of aflibercept makes it a useful second-line agent in mCRC patients progressing after oxaliplatin-based chemotherapy, as well as in those with resistance after bevacizumab.

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