Efficacy of bevacizumab in combination with irinotecan or oxaliplatin as second-line, third-line or later treatment in metastatic colorectal cancer (MCRC) patients

14558 Introduction: Bevacizumab (Bev) is efficient in MCRC patients (pts) as first-line treatment (L1) with 5FU±irinotecan, and with FOLFOX as second-line (L2). It has no efficacy in 3rd or later-line, alone or with 5FU. In Europe, Bev was approved by the EMEA (European Medicines Evaluation Agency) in 2005 and many patients could not received it in L1 before this date. This study evaluated the efficacy of Bev combined to polychemotherapy (CT) in L2, L3 or later-line in CT refractory pts. Methods: Between May 2005 and October 2006, 38 pts (median age: 54.5 years, range:25–82) received Bev combined with CT as L2 (n=18), L3 (n=6), L4 (n=7), L5 or later-line (n=7). Tumor response (OR) was assessed according to RECIST criteria by CT-scan. Results: Tumor sites: 28 colon and 10 rectum. Number of metastatic sites were 1, 2 and more in 16, 13 and 9 cases, mostly hepatic (89%) or pulmonary (42%). Bev (5mg/kg/2weeks) was combined with FOLFIRI (n=24) or FOLFOX (n=14); 299 cycles were administered, mean: 7.9 cycles/pt (range:2–14). OR rate was 42,1%, stabilization 42,1% and was not different according to the line or the CT regimen (table). Initial progressions were rare. Tolerance was acceptable (no perforation and no severe Hypertension). Conclusion: This study reports a significant activity of Bev at the dose of 5mg/kg combined with FOLFOX and/or FOLFIRI in CT refractory pts. These results warrant prospective studies of Bev combined with active CT in CT refractory pts who could not received Bev in the setting of the EMEA authorization. [Table: see text] No significant financial relationships to disclose.

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Disease Management and Resource Use for the Management of Melanoma stage IIIc or IV Positive for BRAF V600 Mutations in Greece

10.52106/2766-3213.1017 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Carayanni V ◽

Gogas H ◽

Bafaloukos D ◽

Boukovinas I ◽

Latsou D ◽

...

Keyword(s):

Resource Use ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Cost Of Treatment ◽

Management Scenario ◽

Third Line ◽

The Cost ◽

Third Line Treatment ◽

First Line Treatment

Objective: Melanoma is one of the most aggressive cancers and is responsible for the majority of skin cancer deaths, with the presence of metastases prognostic for poor survival. At a time when most cancer incidences are falling, the annual incidence of melanoma has risen as rapidly as 4-6% in many European countries, with a substantial economic burden in advanced stages. The objective of this study is the investigation of treatment pathways and healthcare resource use related to advanced BRAF-mutated melanoma in Greece. Methods: This study is based on the information collected by an expert panel comprising of 3 oncologists of major public and private melanoma clinics around Greece. A 3-round survey was undertaken, according to a modified Delphi method. The treatment phases studied were: pre-progression; disease progression and terminal care. Oncology drug costs, medical visits, laboratory tests, imaging examinations, hospitalization and concomitant medications were the resources considered in the context of the Greek National Services Organization (EOPYY). Results: Τhe most common management scenario (80% of cases) in Greece for patients of stage IV BRAF V600 mutated melanoma was: targeted therapies as first line treatment at 95%, followed by immunotherapies at 100% as second line as well as third line treatment at 65% of cases. The weighted annual cost of treatment was 89.215,78 €, (90%CI:62,451.05; 115,980.51) for first line treatment at list price and around 41.584,50 (90%CI:29,109.15; 54,059.85) based on the negotiated price. At second line, the cost of treatment has been estimated between 15,704.272 (90%CI:10,992.990; 20,415.553) and 19,800.92€, (90%CI: 16,489; 30,622) for the two most common management scenarios for immunotherapies. For third line treatment the cost was 37,778.93 (90%CI 26,445.25; 49,112.61€) for the mostly used management scenario (50% ipilimumab). Conclusions: Μetastatic BRAF mutant melanoma requires prolonged and costly treatment with new therapies shown to substantially increase life expectancy. Identifying the appropriate treatment options in order to optimize health outcomes should be an important priority in healthcare system.

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Immediate hypersensitivity reaction followed by successful oral desensitization to ursodiol

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00578-7 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Erika Yue Lee ◽

Christine Song

Keyword(s):

Hypersensitivity Reaction ◽

Primary Biliary Cholangitis ◽

Line Treatment ◽

Second Line ◽

Immediate Hypersensitivity ◽

First Line ◽

Case Presentation ◽

Desensitization Protocol ◽

First Line Treatment ◽

Oral Desensitization

Abstract Background Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization. Case presentation A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol—the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol. Conclusion Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.

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Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

Clinical & Translational Oncology ◽

10.1007/s12094-021-02568-y ◽

2021 ◽

Author(s):

B. González Astorga ◽

F. Salvà Ballabrera ◽

E. Aranda Aguilar ◽

E. Élez Fernández ◽

P. García-Alfonso ◽

...

Keyword(s):

Colorectal Cancer ◽

Therapeutic Option ◽

Scientific Evidence ◽

Treatment Options ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Effective Therapeutic Option ◽

Line Setting ◽

First Line Treatment

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

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Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

International Journal of Molecular Sciences ◽

10.3390/ijms22147717 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7717

Author(s):

Guido Giordano ◽

Pietro Parcesepe ◽

Giuseppina Bruno ◽

Annamaria Piscazzi ◽

Vincenzo Lizzi ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Checkpoint Inhibitors ◽

Line Treatment ◽

Second Line ◽

Wild Type ◽

First Line ◽

Braf Mutations ◽

Mutational Status ◽

First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

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Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Pharmaceuticals ◽

10.3390/ph14020151 ◽

2021 ◽

Vol 14 (2) ◽

pp. 151

Author(s):

Anica Högner ◽

Peter Thuss-Patience

Keyword(s):

Cell Death ◽

Gastric Carcinoma ◽

Programmed Cell Death ◽

Immune Checkpoint ◽

Disease Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

The Usa ◽

First Line Treatment

Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

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Efficacy of Coenzyme Q10 in the Treatment of Cyclic Vomiting Syndrome in Children

10.26420/jpediatrchildhealthcare.2021.1038 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Brezin F ◽

◽

Wiedemann A ◽

Bansept C ◽

Albuisson E ◽

...

Keyword(s):

Coenzyme Q10 ◽

Gastrointestinal Disorder ◽

Cyclic Vomiting Syndrome ◽

Line Treatment ◽

First Line ◽

Excellent Safety Profile ◽

Third Line ◽

One Year ◽

First Line Treatment ◽

Cyclic Vomiting

Cyclic Vomiting Syndrome (CVS) is a chronic functional gastrointestinal disorder related to migraine, characterized by episodic nausea and vomiting. The treatment of CVS remains based on tricyclic antidepressants, triptans and antiepileptics. As mitochondriopathy has been involved in the pathophysiology of CVS, Coenzyme Q10 (CoQ10), a mitochondrial cofactor, has been used as the third line treatment in CVS. Considering the excellent safety profile of CoQ10, we decided to use it as the first line treatment in CVS. We retrospectively studied the evolution of 23 CVS patients who were treated for one year by CoQ10 alone. We recorded the characteristics of patients and their CVS history and compared data obtained the year before and the year following the prescription of CoQ10 treatment. We found a significant decrease in the number of vomiting episodes between the year before and the year after the start of CoQ10 (median [IQR]: 18.0 [15.75] vs. 3.00 [5.0]; p <0.001). This decrease persisted with time (2 and 3 years of treatment). The treatment was very efficient in 17/23 patients and did not decrease the number of vomiting episodes in 3 patients. Only one mild side effect related to the drug has been reported. Conclusions: CoQ10 is an efficient and safe treatment of CVS and should be used as the first line treatment in this episodic syndrome related to migraine.

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First-line treatment with a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor for hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: Population-based outcomes for patients treated in Alberta, Canada.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13020 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13020-e13020

Author(s):

Carla Pires Amaro ◽

Atul Batra ◽

Sasha M. Lupichuk

Keyword(s):

Hormonal Therapy ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Population Based ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Hormone Receptor Positive ◽

Targeted Agent ◽

First Line Treatment

e13020 Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with an aromatase inhibitor (AI) has emerged as the standard first line treatment in patients with hormone receptor positive, human epidermal growth factor receptor-2 (HER-2) negative metastatic breast cancer (MBC). In this analysis, we describe population-based outcomes for first-line treatment with a CDK4/6i combined with an AI. Methods: All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 in a large Canadian province were included. Descriptive statistics were used to summarize patient demographics, tumor and treatment characteristics. Survival distributions were estimated using the Kaplan-Meier method. Multivariate analysis (MVA) using a Cox proportional hazards model was constructed to examine associations between potentially prognostic clinical variables and progression free survival (PFS). Results: A total of 316 patients were included. Median age was 61 years (interquartile range, 53-70 years), 82% were postmenopausal women, 39% had de novo MBC, and 48% had non-visceral disease. Palbociclib was prescribed in 94% of patients and the remaining patients received ribociclib. The CDK4/6i was dose-reduced upfront or during treatment in 47%. While 70% of the patients discontinued treatment due to progression, 30% stopped due to toxicity/patient preference/physician recommendation. With a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7-NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45-3.88; P = 0.001) and dose reduction of the CDK4/6i (HR, 1.51; 95% CI, 1.06-2.16; P = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed (n = 131), 89% received second-line treatment (chemotherapy in 46%, single agent hormonal therapy in 35%, hormonal therapy plus a targeted agent in 15%, and other in 4%). Median time to progression on second line chemotherapy was 9.0 (5.8-17.6) months and second line hormonal therapy +/- targeted agent was 4.0 (3.4-8.6) months (P = 0.012). Conclusions: The real-world outcomes of first-line use of CDK4/6i and AI are encouraging. PR negative tumors and dose reduction appear to be negative prognostic markers. CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favorable PFS and early OS outcomes.

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Tumor characteristics and metastatic sites may predict bevacizumab efficacy in the first-line treatment of metastatic colorectal cancer

Molecular and Clinical Oncology ◽

10.3892/mco.2013.212 ◽

2013 ◽

Vol 2 (1) ◽

pp. 166-170 ◽

Cited By ~ 2

Author(s):

UMUT VAROL ◽

ESIN OKTAY ◽

MUSTAFA YILDIRIM ◽

ZEKI GOKHAN SURMELI ◽

AHMET DIRICAN ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Tumor Characteristics ◽

Line Treatment ◽

First Line ◽

Metastatic Sites ◽

First Line Treatment

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Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for foregut leaks and perforations

Endoscopy ◽

10.1055/s-0043-120442 ◽

2017 ◽

Vol 50 (02) ◽

pp. 148-153 ◽

Cited By ~ 10

Author(s):

Piero Valli ◽

Joachim Mertens ◽

Arne Kröger ◽

Christoph Gubler ◽

Christian Gutschow ◽

...

Keyword(s):

Adverse Events ◽

Success Rate ◽

Vacuum Therapy ◽

Line Treatment ◽

Second Line ◽

Metal Stent ◽

First Line ◽

Novel Technique ◽

Upper Gastrointestinal ◽

First Line Treatment

Abstract Background and study aims Endoluminal vacuum therapy (EVT) has evolved as a promising option for endoscopic treatment of foregut wall injuries in addition to the classic closure techniques using clips or stents. To improve vacuum force and maintain esophageal passage, we combined endosponge treatment with a partially covered self-expandable metal stent (stent-over-sponge; SOS). Patients and methods Twelve patients with infected upper gastrointestinal wall defects were treated with the SOS technique. Results Indications for SOS were anastomotic leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment was used as a first-line treatment in seven patients with a success rate of 71.4 % (5/7) and as a second-line treatment after failed previous EVT treatment in five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in 75 % of patients (9/12). No severe adverse events occurred. Conclusion SOS is an effective method to treat severely infected foregut wall defects in patients where EVT has failed, and also as a first-line treatment. Comparative prospective studies are needed to confirm our preliminary results.

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