FOLFIRI In Patients Research Articles

Phase Ib/IIa study of GC1118 in combination with irinotecan or FOLFIRI in patients with metastatic solid tumors.

3592 Background: GC1118 is a novel anti-EGFR monoclonal antibody which has a unique binding epitope and superior ligand inhibition potential. It showed promising antitumor activity as a single agent in the phase I study. This study aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of GC1118 in combination with irinotecan or FOLFIRI in metastatic solid tumors and evaluate the efficacy of GC1118 plus FOLFIRI as a second line therapy for RAS and BRAF wild-type metastatic colorectal cancer. Methods: Phase 1b part was designed to evaluate weekly GC1118 (starting from 3 mg/kg) in combination with biweekly irinotecan (180mg/m2) or FOLFIRI (irinotecan 180mg/m2, leucovorin 400mg/m2, 5-FU 400 mg/m2 bolus, and 5-FU 2400mg/m2 over 46hrs) in a 3+3 design. In the phase 2a part, the RP2D of GC1118 is administered in combination with FOLFIRI in a Simon’s two stage design with objective response rate (ORR) as the primary endpoint. Results: 13 pts were enrolled in phase 1b and received 3mg/kg of GC1118 with irinotecan (N = 6) or FOLFIRI (N = 7). DLT occurred in 2 pts (G4 neutropenia, G2 rash) in irinotecan arm and 1pt (G3 neutropenia) in FOLFIRI arm with 3mg/kg of GC1118 and it was determined as MTD and RP2D. Adverse events (AE) of grade ≥ 3 included neutropenia (61.5 %), skin rash (15.4 %) and diarrhea (15.4%). Dose reductions due to GC1118-related AE were required in 6 (46.2%) patients. Among 10 response-evaluable pts in phase 1b, best overall response was PR in 3 and SD in 6, and median PFS was 12 months. In stage 1 of phase 2a (N = 9), 4 PR and 5 SD were observed (ORR 44.4%, 95% CI 13.7 – 78.8). We moved to stage 2, and are currently enrolling additional 20 pts. AE of grade ≥ 3 included neutropenia (66.7%), skin rash (22.2%) and diarrhea (11.1%). Updated data of the phase 2a part will be presented at the meeting. Conclusions: The MTD and RP2D of weekly GC1118 in combination with irinotecan or FOLFIRI was 3mg/kg. Preliminary results of GC1118 and FOLFIRI as a 2nd line treatment in mCRC suggests promising antitumor activity and acceptable safety profile. Clinical trial information: NCT03454620 .

Safety of Aflibercept in Metastatic Colorectal Cancer: A Literature Review and Expert Perspective on Clinical and Real-World Data.

Background: Metastatic colorectal cancer (mCRC) represents a substantial health burden globally and an increasing challenge in Asian countries. Treatment options include chemotherapy plus a vascular endothelial growth factor (VEGF) inhibitor (such as bevacizumab, aflibercept or ramucirumab), or anti-epidermal growth factor receptor (EGFR) therapies. Aflibercept, a recombinant fusion protein, has been approved for treatment of mCRC in combination with FOLFIRI for patients whose disease progresses during or after treatment with an oxaliplatin-containing regimen, based on its efficacy and tolerability profile in clinical trials. This report aims to provide an overview of both clinical and real-world evidence and experience on the use of aflibercept in routine clinical practice, with a focus on European, American and Asian populations. Methods: A literature search was conducted in PubMed (on 28th February 2019) using the search terms ("aflibercept") and ("Colorectal"OR"CRC") to identify publications containing information on aflibercept-containing regimens. Results: The adverse events (AE) profile was similar between geographical locations. Across trials, real-world and retrospective studies, grade ≥ 3 hypertension and proteinuria were amongst the most frequently reported AEs. Conclusions: The safety profile of aflibercept is generally manageable and comparable across various geographic locations.

Post hoc safety and effectiveness analysis of aflibercept + FOLFIRI for patients with metastatic colorectal cancer (mCRC) previously treated with antiepidermal growth factor receptor (EGFR) therapy in OZONE.

212 Background: Anti-EGFR therapies are frequently given as first-line therapy for patients with mCRC, while anti-angiogenic therapies may be suitable at any line. Despite improving outcomes for patients with mCRC, there is still an unmet need regarding the optimal treatment sequence. In this post hoc analysis, the safety and effectiveness of aflibercept + FOLFIRI was evaluated for patients with mCRC based on their prior anti-EGFR therapy use. Methods: OZONE is a prospective, multicenter, observational, non-comparative study evaluating patients receiving aflibercept + FOLFIRI in the clinical setting, for 24 months from aflibercept initiation or until death. Patients were retrospectively assessed according to prior use of anti-EGFR therapy (defined as patients who received cetuximab and/or panitumumab as previous anti-cancer therapy). Overall survival (OS) and progression-free survival (PFS) were analyzed by hazard ratios (HR) and 95% confidence intervals (CI); overall response rate (ORR) was analyzed by odds ratios (OR) and 95% CI. Results: Among the overall treated population (N = 766), 19.2% (n = 147) received prior anti-EGFR therapy. Prior anti-EGFR therapy had no significant impact on the median OS (11.47 vs 12.58 months; HR [95% CI] 1.112 [0.889–1.390]), median PFS (5.29 vs 6.24 months; HR [95% CI] 1.022 [0.830–1.260]), or ORR (14.96% vs 18.75%; OR [95% CI] 0.597 [0.332–1.071]) of patients vs those who did not receive prior anti-EGFR therapy. Rates of grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar between patients who did vs did not receive prior anti-EGFR therapy (70.7% vs 67.7%). The most frequently reported grade ≥ 3 TEAEs for patients who did vs did not receive prior anti-EGFR therapy were neutropenia (12.2% vs 15.0%), hypertension (8.8% vs 10.3%), and diarrhea (10.2% vs 9.4%). Conclusions: This post hoc analysis of the OZONE study did not reveal major differences in safety and effectiveness according to prior anti-EGFR therapy. Clinical trial information: ENCEPP/SDPP/4836.

A Phase 2 Trial of SCO-101 in Combination With FOLFIRI for Patients With Metastatic Colorectal Cancer (mCRC) With Acquired Resistance to FOLFIRI

A Phase 2 Trial of SCO-101 in Combination With FOLFIRI for Patients With Metastatic Colorectal Cancer (mCRC) With Acquired Resistance to FOLFIRI

Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers.

BACKGROUNDGemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers (BTC). There is no established second-line therapy, and retrospective reviews report median progression-free survival (PFS) less than 3 mo on second-line therapy. 5-Fluorouracil plus irinotecan (FOLFIRI) is a commonly used regimen in patients with BTC who have progressed on gemcitabine plus platinum, though there is a paucity of data regarding its efficacy in this population.AIMTo assess the efficacy of FOLFIRI in patients with biliary tract cancers.METHODSWe retrospectively identified patients with advanced BTC who were treated with FOLFIRI at MD Anderson, University of Michigan and Mayo Clinic in Jacksonville. Data were collected on patient demographics, BTC subtype, response per RECIST v1.1, progression and survival.RESULTSNinety-eight patients were included of which 74 (75%) had metastatic and 24 (25%) had locally advanced disease at the time of treatment with FOLFIRI. The median age was 60 (range, 22-86) years. The number of patients with extrahepatic cholangiocarcinoma, gall bladder cancer and intrahepatic cholangiocarcinoma were 10, 17 and 71, respectively. FOLFIRI was used as 1st, 2nd, 3rd or 4th – Nth lines in 8, 50, 36 and 4 patients, respectively. Median duration on FOLFIRI in the entire cohort was 2.2 (range, 0.5-8.4) mo. The median PFS and overall survival were 2.4 (95% confidence interval (CI): 1.7-3.1) and 6.6 (95%CI: 4.7-8.4) mo, respectively. Median PFS for patients treated with FOLFIRI in 1st, 2nd, 3rd or 4th – Nth lines were 3.1, 2.5, 2.3 and 1.5 mo, respectively. Eighteen patients received concurrent bevacizumab (n = 13) or EGFR-targeted therapy (n = 5) with FOLFIRI, with a median PFS of 2.7 mo (95%CI: 1.7-5.1).CONCLUSIONIn this largest multi-institution retrospective review of 98 patients with BTC treated with FOLFIRI, efficacy appears to be modest with outcomes similar to other cytotoxic chemotherapy regimens.

Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers

Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers

Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial

BackgroundRegorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in a 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. The aim of this study is to address the efficacy and safety of a dose-adjusted combination of regorafenib and FOLFIRI for patients with mCRC.MethodsA prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with mCRC. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, disease control rate, time to progression, and duration of treatment. Safety assessments will also be recorded.DiscussionDose adjustment for regorafenib and irinotecan makes treatment-related AEs tolerable and makes the concomitant treatment practicable. This study will provide initial evidence regarding the efficacy and safety of a new combination of chemotherapy and a targeted agent for mCRC.Trial registrationClinicalTrials.gov, NCT03880877. Prospectively registered on 19 March 2019.

Abstract 4720: Ataxia telangiectasia mutated (ATM) kinase inhibitor AZD0156 in combination with 5-fluorouracil and irinotecan in preclinical models of colorectal cancer

Abstract Background: AZD0156 is an oral inhibitor of ATM, a serine threonine kinase that plays a key role in DNA damage response associated with DNA double strand breaks. Topoisomerase-I inhibitors like irinotecan induce single-strand DNA breaks, which are converted to double-strand breaks during DNA replication. Thus the combination of AZD0156 and irinotecan is a rational combination for clinical use. Irinotecan is used clinically to treat a variety of malignancies, including colorectal cancer (CRC), usually in combination with 5-fluorouracil (5FU) as FOLFIRI. An ongoing phase 1 clinical trial is evaluating AZD0156 in combination with single-agent irinotecan and FOLFIRI in patients with refractory cancers (NCT02588105). The purpose of this study is to evaluate AZD0156 in combination with irinotecan and 5FU in preclinical models of CRC to help inform clinical use. Methods: Anti-proliferative effects of single-agent AZD0156 and combination therapy with SN38 (active metabolite of irinotecan) and 5FU were evaluated in CRC cell lines using the Cell-Titer Glo assay. Immunoblotting and cell cycle analysis were performed to determine the mechanism of enhanced combination effects. Four CRC patient derived xenograft (PDX) models were treated with AZD0156, irinotecan, and 5FU alone and in combination for assessment of tumor growth inhibition (TGI). Results: An enhanced antiproliferative effect was observed with the combination treatment over either single agent. A more significant synergistic effect was demonstrated with the combination of AZD0156 and SN38 as compared with the combination of AZD0156 and 5FU. Cell cycle data demonstrated enhanced cell cycle arrest with combination therapy as compared to single agents. Immunoblotting results suggest a decrease in phosphorylated gamma-H2AX in cell lines treated with combination therapies. Increased TGI was observed in CRC PDX models treated with the combination of AZD0156 and irinotecan as compared to single-agent therapy in 3 of 4 models. There was not a significant change in TGI with the addition of 5FU for triplet therapy in the majority of models. Conclusions: The combination of AZD0156 with irinotecan is synergistic in in vitro models and is associated with increased TGI in CRC PDX in vivo models. The addition of 5FU to AZD0156 and irinotecan did not result in increased TGI as compared to doublet therapy in CRC PDX models, though did not decrease the AZD0156/irinotecan combination effect. An ongoing clinical trial is evaluating this combination in patients with cancers refractory to standard treatments (NCT02588105). Citation Format: S. Lindsey Davis, Marina I. Schlaepfer, Stacey M. Bagby, Sarah J. Hartman, Betelehem W. Yacob, Tonia Tse, Dennis M. Simmons, Jennifer R. Diamond, Christopher H. Lieu, Alexis D. Leal, Elaine B. Cadogan, Gareth D. Hughes, Stephen T. Durant, Wells A. Messersmith, Todd M. Pitts. Ataxia telangiectasia mutated (ATM) kinase inhibitor AZD0156 in combination with 5-fluorouracil and irinotecan in preclinical models of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4720.

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer

BackgroundPreclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC).MethodsIn the dose-escalation phase, patients received AA (0.2–1.5 g/kg, 3-h infusion, once daily, days 1–3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed.ResultsThirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1–3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3–4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF.ConclusionsThe favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC.Trial registrationClinicalTrial.gov Identifier: NCT02969681.

ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab.

TPS720 Background: Dual variable domain immunoglobulin ABT-165 targets human vascular endothelial growth factor (VEGF) and delta-like ligand 4 (DLL4). Combined VEGF and DLL4 blockade increased inhibition of subcutaneous xenograft growth of human colon cancer-derived cell lines versus blockade of either axis alone. In vivo, ABT-165 plus chemotherapy (CT) induced tumor regression with improved efficacy, vs anti-VEGF monoclonal antibody plus CT. In a phase 1 study, tolerable recommended phase 2 dose was identified for ABT-165 plus FOLFIRI and showed promising efficacy. This phase 2 trial in progress assesses efficacy/safety of ABT-165 plus FOLFIRI vs bevacizumab (bev) plus FOLFIRI in patients with second-line mCRC. Methods: This is an open-label, multicenter, phase 2 randomized (1:1) trial (NCT03368859) in patients (≥ 18 years; Eastern Cooperative performance status: 0–1) with histologically/cytologically confirmed mCRC who progressed after fluoropyrimidine/oxaliplatin and bev. ABT-165 (2.5 mg/kg) plus FOLFIRI (irinotecan: 180 mg/m2; leucovorin: 400 mg/m2; fluorouracil bolus: 400 mg/m2, infusion: 2400 mg/m2) or bev (5 mg/kg) plus FOLFIRI are given intravenously on day 1 of each 14-day cycle, until disease progression/intolerable toxicity. Primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), and safety. Exploratory endpoints include biomarkers predictive for efficacy/safety, correlation of DLL4 levels with PFS, OS, and ORR, pharmacodynamic effects, and efficacy/safety-exposure relationships in ABT-165 arm. Hazard ratios of PFS and OS comparing the 2 groups are estimated using Cox proportional hazard model. Kaplan-Meier methodology is used to estimate PFS and OS curves, median PFS and OS, and their 90% confidence intervals. Safety is assessed by ABT-165 exposure, adverse events (AEs), serious AEs, all deaths, and changes in laboratory data and vital signs. Archival tissue is collected and evaluated for DLL4 expression and angiogenesis signature. Approximately 100 patients are planned to be enrolled, with recruitment initiated January 2018. Clinical trial information: NCT03368859.

104P - Efficacy of ramucirumab in combination with second-line or salvage-line FOLFIRI in patients with metastatic colorectal cancer

104P - Efficacy of ramucirumab in combination with second-line or salvage-line FOLFIRI in patients with metastatic colorectal cancer

P2-094 - The safety and efficacy of FOLFIRI combined Ramucirumab for metastatic colorectal cancer as 2nd line

The current approval is based on the results of the RAISE study, a phase 3 trial that compared Ramucirumab (Rmab) plus FOLFIRI to placebo plus FOLFIRI in patients with metastatic colorectal cancer who experienced disease progression after prior therapy. Rmab is a vascular endothelial growth factor receptor 2 antagonist and is seen as a successor to the first angiogenesis inhibitor, bevacizumab (Bmab). We have been reporting that safety and efficacy of FOLFIRI combined Rmab for metastatic colorectal cancer as 2nd line. Methods:Between June 2017 and January 2018, we investigated to safety and efficacy of FOLFIRI combined Rmab for metastatic colorectal cancer as 2nd line. Eligible patients had confirmed colorectal adenocarcinoma: had a treatment history of Bmab combined chemotherapy. Patients have measurable lesions have an Eastern Cooperative Oncology Group performance status (PS) of between 0 and 2: and have adequate bone-marrow, hepatic, renal functions and under 2 plus proteinuria within 7 days of enrolment. Patients characteristics. Patients received either intravenous ramucirumab 8 mg/kg or placebo every 2 weeks until disease progression, unacceptable toxicity, or death. Results. Patient characteristics as follow; twelve patients enrolled, gender. male were 8 and female were 4, median age was 73 years, PS was 1, the response rate and disease control rate were 50% and 83%, respectively. The overall survival has still been investigating. Hematological adverse events as follows; 54% of leukopenia, 55% of anemia, 28% of thrombocytopenia. Non-hematological adverse events as follows 62% of proteinuria and 25% of leg edema. However we do not have any grade4 adverse events. The safety and efficacy in clinical situation of Rmab as 2nd line chemotherapy was demonstrated. Conclusion: Rmab has promising efficacy and a tolerable safety profile in patients with metastatic colorectal cancer who are refractory or intolerant to Bmab combined chemotherapies.

P-296 - ABT-165 plus FOLFIRI vs bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab - Trial in progress

P-296 - ABT-165 plus FOLFIRI vs bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab - Trial in progress

P-234 - Phase 1b open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABT-165 plus FOLFIRI in patients with second-line (2L) colorectal cancer (CRC)

P-234 - Phase 1b open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABT-165 plus FOLFIRI in patients with second-line (2L) colorectal cancer (CRC)

Impact of primary tumor side on outcomes of every-2-weeks (q2w) cetuximab + first-line FOLFOX or FOLFIRI in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 2 APEC trial.

Impact of primary tumor side on outcomes of every-2-weeks (q2w) cetuximab + first-line FOLFOX or FOLFIRI in patients with <i>RAS</i> wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 2 APEC trial.

ABT-165 plus FOLFIRI vs bevacizumab (bev) plus FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bev.

TPS3619Background: The dual variable domain immunoglobulin ABT-165 targets human vascular endothelial growth factor (VEGF) and delta-like ligand 4 (DLL4). Combined VEGF and DLL4 blockade increased ...

A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours

BackgroundVeliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid tumours.MethodsPatients received veliparib (10–270 mg BID, days 1–5, 15–19) and FOLFIRI (days 1–3, 15–17) in three regimens containing 5-fluorouracil 2,400 mg/m2: irinotecan 150 mg/m2 and folinic acid 400 mg/m2 (part 1); irinotecan 180 mg/m2, folinic acid 400 mg/m2, and 5-fluorouracil 400 mg/m2 bolus (part 2), or irinotecan 180 mg/m2 (part 3). The RP2D was further evaluated in safety expansion cohorts. Preliminary antitumour activity was also assessed.ResultsNinety-two patients received ≥1 veliparib dose. MTD was not reached; RP2D was set at 200 mg BID veliparib plus FOLFIRI (without 5-fluorouracil bolus). Most common treatment-emergent adverse events were neutropenia (66.3%), diarrhoea, and nausea (60.9% each). Dose-limiting toxicities (n = 4) were grade 3 gastritis and grade 4 neutropenia and febrile neutropenia. Veliparib exposure was dose-proportional, with no effects on the pharmacokinetics of FOLFIRI components. Fifteen patients had a partial response (objective response rate, 17.6%).ConclusionsThe acceptable safety profile and preliminary antitumour activity of veliparib plus FOLFIRI support further evaluation of this combination.

Trastuzumab in Combination with FOLFIRI in Patients with Advanced HER2-Positive Gastro-Esophageal Adenocarcinoma: A Retrospective Multicenter AGEO Study.

Trastuzumab with fluoropyrimidine and cisplatin is the standard first-line treatment in patients with HER2-positive advanced gastro-esophageal adenocarcinoma. However, there are no safety and efficacy data of trastuzumab with FOLFIRI. To evaluate safety and efficacy of FOLFIRI plus trastuzumab in patients with HER2-positive advanced gastro-esophageal adenocarcinoma. This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastro-esophageal adenocarcinoma treated with FOLFIRI plus trastuzumab between 2012 and 2015. A total of 33 patients (median age, 60.3; performance status 0-1, 78.8%) with HER2-positive advanced gastro-esophageal adenocarcinoma treated with FOLFIRI plus trastuzumab in first (n=3), second (n=20) or third (n=10) line of chemotherapy were included. There was one case of a severe non-hematological adverse event corresponding to a left ventricular systolic dysfunction. The most common hematological grade 3 or 4 adverse events were neutropenia (12.9%) and thrombocytopenia (6.4%). There was no febrile neutropenia. For patients treated with FOLFIRI plus trastuzumab in second-line chemotherapy, the median overall survival was 9.5months. This is the first western population-based study of FOLFIRI plus trastuzumab reporting a satisfactory safety profile and a potential efficacy in advanced HER2-positive gastric cancer.

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer.

Background:To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC).Methods:154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression.Results:Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease. Median response duration was longer in RAS WT (13.0 months) vs RAS MT (5.8 months) (hazard ratio (HR): 0.16). Median progression-free survival was longer in RAS WT vs MT (11.2 vs 7.3 months; HR, 0.37) and was also longer in RAS WT/BRAF WT vs RAS or BRAF MT (13.2 vs 6.9 months; HR, 0.25). Incidence of adverse events was similar regardless of RAS/BRAF status, and no new safety signals were noted. Among patients with RAS WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression.Conclusions:First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with RAS WT and RAS WT/BRAF WT vs MT mCRC tumours and was well tolerated.

The role of preoperative chemotherapy for colorectal cancer metastases in the liver with the lack of RAS mutations

Colorectal cancer (CRC) is one of the most common malignancies, occupying the third place in the world among malignant tumors morbidity rate and the 4th place on the causes of death. Every year in the world there are diagnosed more than 1.3 millions of new cases of the disease. The mortality rate continues to be one of the most common causes in the structure of cancer incidence. In Russia, each year there are diagnosed more than 60 thousands of new cases of colorectal cancer. For the last time the incidence increased by 11%, out of them more than 17 thousands patients show newly diagnosed distant metastases. In the absolute majority of cases metastases in the liver are firstly detected in 2-3 years. Liver is the organ- the most commonly affected by metastases. Methods of medicinal treatment of CRC metastases are of great importance and allowed to greatly improve the life expectancy of patients. Median overall survival (OS) is 35-40 months. The one of the last achievement of the modern drug therapy of metastatic CRC was the appearance of the preparation Cetuximab. Blocking of the KRAS gene is a key compartment of the signaling pathways that transmit extracellular growth signals from the surface of the cell to the nucleus. Further signals are transmitted via the cascade into the cellular nucleus, regulating cell growth, proliferation, angiogenesis, invasion and metastasis. Results of the research of PRIME, PEAK and FIRE-3 confirm the advantage of supplement ofpanitumumab or cetuximab to chemotherapy regimens FOLFOX or FOLFIRI in patients with wild-type Ras.