Meta-analysis of outcomes of VEGF and EGFR targeted biologic therapy in relapsed metastatic colorectal cancer (mCRC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 534-534 ◽  
Author(s):  
David Chan ◽  
Eva Segelov ◽  
Jeremy David Shapiro ◽  
Timothy Jay Price ◽  
Christos Stelios Karapetis ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Biologic Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Biologic Agents ◽  
First Line ◽  
Grade 3 ◽  
Line Setting ◽  
The Impact

534 Background: Biologic therapies used in treatment of mCRC are expensive and there is debate about their value. We examined the impact of biologic therapy on overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 toxicity for patients beyond first-line treatment. Methods: MEDLINE, EMBASE, and Cochrane libraries were searched for randomized studies in relapsed mCRC comparing treatment containing targeted therapy to the same treatment without targeted therapy. Biologic agents were classed as: EGFR-inhibitors (EGFR-I), VEGF antibody/trap and VEGFR tyrosine kinase inhibitors (TKI). Only KRAS wild-type patients were included for EGFR-I analysis. Results were aggregated according to standard meta-analytic techniques. Results: 10 studies evaluating 5,847 patients were identified. Considering subgroups and lines, OS and PFS benefit was demonstrated in all groups across all lines except for OS in 2nd line EGFR-I use (which may be due to subsequent crossover). A benefit to ORR was seen with EGFR-I 2nd line (Pooled ORR benefit +24%, Odds Ratio (OR) 4.44, 95% CI 3.20-6.18), EGFR-I 3rd line and beyond (Pooled ORR benefit +16%), VEGF antibody/trap (Pooled ORR benefit +7.2%, OR 2.00, 95% CI 1.57-2.54) and VEGFR TKI (Pooled ORR benefit +1.9%, OR 2.05, 95% CI 1.27-3.30). The risk of grade 3/4 toxicity was greater with the addition of all targeted agents. Conclusions: The use of VEGF and EGFR targeted biologic agents beyond first-line setting in mCRC results in a benefit to OS, PFS and ORR for all agents except for OS benefit with second-line EGFR-I. This benefit comes at the cost of increased toxicity. [Table: see text]

scholarly journals Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
R.-D. Hofheinz ◽  
U. Ronellenfitsch ◽  
S. Kubicka ◽  
A. Falcone ◽  
I. Burkholder ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Optimal Sequence ◽  
Primary Endpoints ◽  
Disease Stabilization ◽  
Antiangiogenic Drugs ◽  
The Impact

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis.Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression.Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58).Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

scholarly journals Efficacy and safety of combined androgen blockade with antiandrogen for advanced prostate cancer

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Y. Yang ◽  
R. Chen ◽  
T. Sun ◽  
L. Zhao ◽  
F. Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
First Line ◽  
Combined Androgen Blockade ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Grade 3 ◽  
Androgen Blockade

Background Combined androgen blockade (cab) is a promising treatment modality for prostate cancer (pca). In the present meta-analysis, we compared the efficacy and safety of first-line cab using an antiandrogen (aa) with castration monotherapy in patients with advanced pca.Methods PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (rcts) published through 12 December 2016. Hazard ratios (hrs) with 95% confidence intervals (cis) were determined for primary outcomes: overall survival (os) and progression-free survival (pfs). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal aa (nsaa) compared with a steroidal aa (saa).Results Compared with castration monotherapy, cab using an aa was associated with significantly improved os (n = 14; hr: 0.90; 95% ci: 0.84 to 0.97; p = 0.003) and pfs (n = 13; hr: 0.89; 95% ci: 0.80 to 1.00; p = 0.04). No significant difference in os (p = 0.71) and pfs (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, cab using a nsaa was associated with significantly improved os (hr: 0.88; 95% ci: 0.82 to 0.95; p = 0.0009) and pfs (hr: 0.85; 95% ci: 0.73 to 0.98; p = 0.007)—a result that was not achieved with cab using a saa. The safety profiles of cab and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with cab using an aa.Conclusions Compared with castration monotherapy, first-line cab therapy with an aa, especially a nsaa, resulted in significantly improved os and pfs, and had an acceptable safety profile in patients with advanced pca.

Meta Analysis of Grade 3 and/or 4 Toxicities in Low-Grade Non-Hodgkin Lymphoma (LG-NHL) Patients Receiving Maintenance Rituximab (MR) Therapy: Impact of Schedule on Toxicity

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2704-2704
Author(s):  
Chadi Nabhan ◽  
Dana Villines ◽  
Tina V. Valdez ◽  
Michele Ghielmini ◽  
Shu-Fang Hsu Schmitz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Research Funding ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Comparative Trial ◽  
Progression Free Survival ◽  
Low Grade ◽  
Front Line ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 2704 Background: MR has improved the outcome and progression-free survival (PFS) in patients with follicular lymphoma (FL) in front-line and relapsed settings. However, maintenance schedules have been empirically designed based on either B-cell depletion kinetics or rituximab levels, with no consensus on the optimal regimen. Overall, toxicities have been predictable and tolerable but the impact of MR schedule on toxicities has not been previously reported and could influence selection of maintenance regimens. Methods: Using PubMed, prospective clinical trials employing MR were identified. Data presented in abstract form or at meetings were deemed incomplete and thus excluded. Data were analyzed from published manuscripts as percentages of subjects experiencing an adverse event (AE). Percentages were considered as the unit of analysis as this adjusted for the uneven sample sizes. Data were collected for overall Grade 3 and/or Grade 4 toxicity (AE reported at any phase of treatment) and was further categorized as AE occurring during initial treatment or during MR. Grade 1 and 2 toxicities were excluded from meta-analysis, given lack of consistent reporting. No grade 5 toxicities were reported. The incidence, severity, and type of toxicity was analyzed by type of induction (Rituximab (R) vs. R plus chemotherapy), histology (FL vs. FL plus other LG-NHL), setting (front-line vs. relapsed), and MR schedule (one dose every 2 months vs. one dose every 3 months vs. 4 doses every 6 months). Results: Nine clinical trials involving 1,928 patients were included in this Meta analysis (4 of which were randomized controlled in the MR phase). Of those, 1,004 patients received MR. The mean percentage of Grade 3/4 toxicities during any phase of treatment was 26% (95% CI = 0.12–51.88) but when restricted to the MR phase; it was 12.88% (95% CI = 6.50–19.26). Toxicities were numerically higher in patients receiving R induction plus chemotherapy versus R induction alone and in patients receiving MR for relapsed disease versus newly diagnosed patients, but did not reach statistical significance (P = 0.661 and 0.517, respectively). However, patients receiving MR every 2 months were significantly more likely to develop grade 3 and 4 toxicities compared to patients receiving MR every 6 months (P = 0.005). No statistical differences were demonstrated between the 2 vs. 3 months schedules or when comparing the 3 vs. 6 months schedules (P = 0.342 and 0.267, respectively) (Table 1). Statistically significant differences were also found in studies restricted to FL versus others allowing non-FL histologies (P = 0.025) with the FL patients experiencing more toxicity than others. The most frequently reported toxicities were neutropenia and infections. There were no treatment-related deaths in any of the arms. Conclusions: Approximately 13% of patients receiving MR experience grade 3 and/or 4 toxicities, mainly consisting of neutropenia and infections. MR given every 6 months appears to provide the least grade 3 and 4 toxicities. There is a suggestion of increased toxicity in FL histologies. It is important to note that this meta-analysis did not address efficacy and only a true comparative trial can definitively establish the relative risk/benefit ratios amongst MR schedules. Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Smith:Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Phase II study of weekly scheduled irinotecan and capecitabine treatment in advanced colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14644-e14644
Author(s):  
Wenhua Li ◽  
Jin Li ◽  
Jianming Xu ◽  
Lin Shen ◽  
Tianshu Liu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Current Phase ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Severe Diarrhea ◽  
Grade 3 ◽  
Line Setting

e14644 Background: The clinical application of combination therapy of irinotecan and capecitabine is at a standstill due to the consideration on severe diarrhea. The aim of the current phase II study was to explore the optimal administration mode of these two drugs, and evaluate the safety and efficacy of weekly-scheduled XELIRI regimen (wXELIRI) in mCRC pts. Methods: Pts with unresectable, histologically confirmed mCRC were enrolled to receive wXELIRI: irinotecan 90mg/m(2) on Day 1 and capecitabine 1200 mg/m(2) bid on Days 1-5 weekly. Both the first-line pts and second-line treatment pts who failed with FOLFOX or XELOX were eligible. The primary endpoint was rate of Grade 3/4 diarrhea. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and other safeties. Results: From January 2011 to May 2012, totally 43 pts with measurable mCRC were enrolled, 18 of them were male and 25 were female. The median age was 60 yrs (range 32-70). No Grade 4 diarrhea was observed and the rate of grade 3 diarrhea was 4.7%. The most common Grade 3/4 toxicities included leucocyte(11.6%), neutrophile (18.6%), vomiting (4.7%), fatigue (2.3%), hand-foot-syndrome (2.3%) . With a median follow-up of 19.0 months, 23 PFS events were observed. The mPFS for all the 43 pts was 6.1 mons and the mOS was 15.5 mons. For the 31 first-line treatment pts, the mPFS was 7.5 mons and the mOS has not reached. In the second-line treatment group (12 pts), the mPFS was 5.4 mons and mOS was 13.8 mons. Conclusions: The weekly-scheduled irinotecan and capecitabine combination has a low rate of severe diarrhea and acceptable toxicity profile. It could be an alternative regimen for mCRC pts, especially in the second-line setting. Clinical trial information: NCT01322152.

scholarly journals A population-based study examining the effect of tyrosine kinase inhibitors on survival in metastatic renal cell carcinoma in Alberta and the role of nephrectomy prior to treatment

2013 ◽  
Vol 3 (4) ◽  
pp. 281 ◽  
Author(s):  
Mark Warren ◽  
Peter M. Venner ◽  
Scott North ◽  
Tina Cheng ◽  
Chris Venner ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Population Based ◽  
First Line ◽  
Line Setting ◽  
The Impact

Background: We performed a retrospective population-based studyto assess the impact of tyrosine kinase inhibitors (TKIs) on overallsurvival (OS) in patients treated for metastatic renal cell carcinoma(mRCC) in Alberta, Canada and to assess the impact of nephrectomyon OS in patients treated with TKIs.Methods: We identified 134 patients who began taking a TKIbetween December 2003 and June 2007 for mRCC in Alberta. Wecompared survival in this group to that in an earlier cohort of141 pa tients treated with interferon-α (IFN-α) between May 1995and March 2003. We used the Kaplan–Meier method to determineOS, and we used a Cox proportional hazards model to determinehazard ratios (HRs) and confidence intervals (CIs). We performedmultivariate analysis to assess the impact of neprhectomy on OS.Results: Of the 134 patients treated with TKIs, 81 received treatmentin the first-line setting, whereas 53 received treatment after priorIFN-α therapy. All 141 patients from the IFN-α cohort receivedtreatment in the first-line setting. Patients treated with TKIs had animproved OS compared with the IFN-α cohort (HR 0.61, 95% CI0.45–0.83, p = 0.001). The median OS was 18 months in the TKIgroup and 10 months in the IFN-α group. The benefit of TKIs wasconfined to favourable and intermediate risk groups according tothe Memorial Sloan-Kettering Cancer Center prognostic model.Prior nephrectomy was associated with improved OS in the TKIcohort, independent of other prognostic factors.Conclusion: Tyrosine kinase inhibitors improve OS compared withIFN-α in mRCC. In patients treated with TKIs, prior nephrectomyis associated with improved survival independent of other prognosticvariables.Contexte : Une étude rétrospective de population a été menée afind’évaluer l’effet des inhibiteurs de la tyrosine-kinase (ITK) sur lasurvie globale (SG) des patients atteints d’un néphrocarcinomemétastatique et d’évaluer l’impact d’une néphrectomie sur la SGdes patients traités par ITK.Méthodes : Cent trente-quatre patients en Alberta ont entrepris untraitement par ITK entre decembre 2003 et juin 2007 en raisond’un néphrocarcinome. On a comparé les taux de survie dans cegroupe avec ceux d’un groupe de 141 patients ayant entrepris untraitement de première intention par IFN-α entre mai 1995 et mars2003. La survie globale a été calculée à l’aide de la méthode deKaplan Meier, et le risque relatif (RR) et les intervalles de confiance(IC) ont été calculés à l’aide du modèle des risques proportionnelsde Cox. Une analyse multivariée a permis d’évaluer l’impact dela néphrectomie sur la SG dans la population globale de l’étuded’une part et chez les patients traités par ITK d’autre part.Résultats : Les 134 patients ayant entrepris un traitement par ITK ontété répartis ainsi : traitement de première intention, 81 patients, ettraitement de seconde intention après un traitement par IFN-α,53 patients. Les patients traités par ITK ont montré une SG supérieurepar rapport aux patients traités par IFN-α (RR 0,61, IC à 95 % 0,45–0,83, p = 0,001). La SG médiane était de 18 mois chez les patientstraités par ITK et de 10 mois chez les patients traités par IFN-α. Letraitement par ITK n’a eu un avantage que chez les patients atteintsde néphrocarcinome métastatique présentant un risque faible ouintermédiaire selon le modèle du Memorial Sloan-Kettering CancerCener. Une néphrectomie antérieure a été associée à une meilleureSG dans la cohorte traitée par ITK, indépendamment des autres facteurspronostics.Conclusion : Le traitement par ITK a amélioré la SG par rapport autraitement par IFN-α dans une population « réelle ». Une néphrectomieantérieure a été associée à une SG supérieure chez lespatients traités par ITK.

scholarly journals Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 484 ◽  
Author(s):  
Sara Pusceddu ◽  
Michele Ghidini ◽  
Martina Torchio ◽  
Francesca Corti ◽  
Gianluca Tomasello ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Febrile Neutropenia ◽  
Meta Analysis ◽  
Real Life ◽  
Metastatic Pancreatic Cancer ◽  
Cochrane Library ◽  
First Line ◽  
Risk Of Death ◽  
Grade 3 ◽  
Line Setting

Gemcitabine and nab-paclitaxel (GEM-NAB) and the combination of 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX) are valid first-line options for advanced or metastatic pancreatic cancer (mPC). However, no randomized trials comparing the two schemes have been performed. This meta-analysis aims to compare GEM-NAB and FOLFIRINOX in terms of safety and effectiveness, taking into account data from real-life studies on mPC. We systematically searched PubMed, EMBASE and Cochrane library up to November 2018 to identify retrospective or cohort studies on mPC comparing GEM-NAB and FOLFIRINOX. We included 16 retrospective studies, including 3813 patients (2123 treated with GEM-NAB and 1690 treated with FOLFIRINOX). Despite a median weighted overall survival (OS) difference in favor of FOLFIRINOX (mean difference: 1.15, 95% confidence interval CI 0.08–2.22, p = 0.03), in whole population OS was similar (hazard ratio (HR = 0.99, 95% CI 0.84–1.16; p = 0.9). PFS was also not different between the two arms (HR = 0.88, 95% CI 0.71–1.1; p = 0.26). The overall response rate was similar (25 vs. 24% with GEM-NAB and FOLFIRINOX). Among grade 3–4 toxicities, neutropenia, febrile neutropenia, and nausea were lower with GEM-NAB, while neurotoxicity and anemia were lower with FOLFIRINOX. In conclusion, despite a numerically longer median OS with FOLFIRINOX as compared to GEM-NAB, the overall risk of death and progression were similar. Their toxicity was different with less nausea, neutropenia, and febrile neutropenia with GEM-NAB, as compared to less neurotoxicity and anemia with FOLFIRINOX. Therefore, analysis of non-randomized “real world” studies to date has not provided evidence of a major benefit of one regimen over the other.

scholarly journals Cisplatin, Fluorouracil in Bolus Injection, and Leucovorin in First-Line Therapy for Advanced Gastric Cancer as an Alternative to Protocols With Infusional Fluorouracil

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Rafael C. Coelho ◽  
Pedro D.P. Abreu ◽  
Mariana R. Monteiro ◽  
Ana Paula Stramosk ◽  
Alvaro Henrique I. Garces ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Progression Free Survival ◽  
Median Number ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Line Setting ◽  
Platinum Agents

PURPOSE Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide. Platinum agents and fluoropyrimidines are the main compounds used in the first-line setting for advanced GC. Given the activity of fluorouracil (FU) bolus, the PFL protocol, a chemotherapy regimen combining cisplatin, FU bolus, and leucovorin, was incorporated at the Brazilian National Cancer Institute, because this schedule does not require hospitalization or infusion pumps. This study aims to evaluate the outcomes of PFL in the first-line setting for patients with advanced GC. MATERIALS AND METHODS This was a retrospective cohort study evaluating patients with advanced GC treated in the first-line setting with cisplatin 80 mg/m2 on day 1 and FU bolus 400 mg/m2 plus leucovorin 20 mg/m2 on days 1, 8, 15, and 22 every 4 weeks, from January 2008 to December 2014. RESULTS A total of 109 patients were enrolled. The median number of cycles received per patient was four (one to 11). Complete responses were achieved in 6.4% and partial responses in 14.7%. Median progression-free survival was 6.3 months (95% CI, 5.08 to 7.58 months) and median overall survival was 8.3 months (95% CI, 6.79 to 9.87 months). Thirty-four (31.2%) patients were alive in 1 year. Grade 3 and 4 adverse events were experienced by 26.6% and 3.7% of patients, respectively, with dose reduction necessary in 9.1%. CONCLUSION PFL is active in advanced GC and could be an alternative for FU continuous infusion protocols in institutions with limited resources and/or low budget, which is the reality in many nations all over the world.

scholarly journals The impact of complete chemotherapy stop on the overall survival of patients with advanced colorectal cancer in first-line setting: A meta-analysis of randomized trials

2015 ◽  
Vol 54 (10) ◽  
pp. 1737-1746 ◽  
Author(s):  
Allan Andresson Lima Pereira ◽  
Juliana Florinda de Mendonça Rego ◽  
Rodrigo Ramela Munhoz ◽  
Paulo Marcelo Hoff ◽  
Andre Deeke Sasse ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Randomized Trials ◽  
Advanced Colorectal Cancer ◽  
Meta Analysis ◽  
First Line ◽  
Line Setting ◽  
The Impact

scholarly journals The Efficacy and Safety of Treatment Regimens Used in the First-Line Setting in Metastatic Pancreatic Cancer Patients: A Multicenter Real-Life Study

2021 ◽  
Author(s):  
Nadiye Akdeniz ◽  
Muhammet Ali Kaplan ◽  
Mevlüde İnanç ◽  
Doğan Uncu ◽  
Yakup Ergün ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Real Life ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
First Line ◽  
Free Survival ◽  
Life Study ◽  
Treatment Regimens ◽  
Grade 3 ◽  
Line Setting

Abstract Purpose: To compare the efficacy and toxicity of three different chemotherapy regimens used as first-line treatments in the real-life management of metastatic pancreatic cancer (mPC). Methods: A total of 218 patients diagnosed with mPC at the time of initial admission were included in this multicenter study. Gemcitabine (Gem, n=71), Gemcitabine-cisplatin (Gem-Cis, n=91) and FOLFIRINOX (FFX, n=56) treatments were compared in terms of efficacy and treatment-related toxicity. Results: Overall response rate was significantly higher in the FFX group (50.0%) than in the Gem (28.2%) and Gem-Cis (27.5%) groups (p=0.010).Median progression-free survival (8.4 vs. 4.6 and 5.5 months, respectively, p<0.001) and overall survival (16.4 vs. 8.1 and 8.7 months, respectively, p=0.002) were significantly longer in theFFX group than in the Gem and Gem-Cis groups. Toxicity of any grade was noted in 46(64.8%), 56(61.5%) and 49(87.5%) patients in the Gem, Gem-Cis and FFX groups, respectively (p=0.003).Of the grade 3-4 toxicities, weakness/fatigue and mucositis were reported only in the FFX group (5.4% and 3.6%, respectively). Grade 3-4 diarrhea (10.7%, 0.0%, 2.2%, respectively) and neutropenia (25%, 4.2% and 5.5%, respectively) were more common in the FFX group than in the Gem and Gem-Cis groups. Conclusion: In conclusion, our findings indicate that FFX regimen provides a significant advantage over the other treatment regimens in terms of response rates and survival. Treatment toxicity was more frequent but manageable with the FFX regimen.FFX seems to be a preferable regimen in the first-line treatment of the younger and fit patients diagnosed with mPC.

scholarly journals Beyond First-Line Immune Checkpoint Inhibitor Therapy in Patients With Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Rohini Sharma ◽  
Leila Motedayen Aval
Keyword(s):  
Immune Checkpoint ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hepatocellular Cancer ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Second Line ◽  
Research Strategies ◽  
First Line ◽  
Line Setting

Until recently, the treatment landscape for hepatocellular cancer (HCC) was dominated by tyrosine kinase inhibitors (TKIs) which offered an overall survival (OS) benefit when used both in the first-and second-line setting compared to best supportive care. However, the treatment landscape has changed with the introduction of immune checkpoint inhibitors (ICIs) for the treatment of HCC with significant improvement in OS and progression free survival reported with combination atezolizumab and bevacizumab compared to sorafenib in the first-line setting. Nonetheless, the response to ICIs is 20–30% and invariably patients will progress. What remains unclear is which therapeutics should be used following ICI exposure. Extrapolating from the evidence base in renal cell carcinoma, subsequent therapy with TKIs offers both a response and survival benefit and are recommended by European guidelines. However, there are a number of novel therapies emerging that target mechanisms of ICI resistance that hold promise both in combination with ICI or as subsequent therapy. This paper will discuss the evidence for ICIs in HCC, the position of second-line therapies following ICIs and research strategies moving forward.

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