Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma beyond progression of sorafenib treatment: A real-world evidence and in vitro assessment with protein phosphorylation array.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 485-485
Author(s):  
Yasushi Sato ◽  
Tetsu Tomonari ◽  
Hironori Tanaka ◽  
Takahiro Tanaka ◽  
Akihiro Hirao ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Array Analysis ◽  
Third Line ◽  
Protein Array Analysis ◽  
Third Line Treatment

485 Background: No information is available on the efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy. We evaluated the characteristics and the therapeutic efficacy and safety of LEN as a second- and third-line treatment as well as first- treatment for unresectable HCC patients in clinical settings. Moreover, to rationalize these clinical findings in vitro, we assessed the anti-tumor activity of LEN on SOR-resistant cell line and performed a comprehensive phosphorylated protein array analysis associated with 377 signal transduction pathways using SOR-resistant and parental HCC cells. Methods: We retrospectively enrolled 51 unresectable HCC patients. Radiologic responses in 41 patients were evaluated by modified RECIST. Active signal transduction pathways in the cells were identified by protein array analysis, including 1205 proteins. Results: The evaluated patients comprised 25 TKI-naive (first- line), 7 intolerant to SOR (second-line), and 9 patients resistant to regorafenib (third-line). The ORRs were 64% in first-line, 42.8% in second-line, and 22.2% in third-line groups (first-line vs. third-line p< 0.05). The OS in the first-line was significantly longer than that in third-line group ( p< 0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated in the second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 (30 μM) was significantly higher than that against PLC/PRF5 (6.4 μM). LEN significantly inhibited more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than in PLC/PRF5-R2 cells. Conclusions: Our study indicates that LEN was active and safe in the second/third-line treatment for unresectable HCC. LEN seems more effective for HCC patients with better hepatic reserve function, or before TKI-resistance is acquired because of the partial cross-resistance to SOR.

scholarly journals Therapeutic Efficacy and Safety of Lenvatinib for Unresectable Hepatocellular Carcinoma Beyond Progression with Sorafenib

2020 ◽  
Author(s):  
Tetsu Tomonari ◽  
Yasushi Sato ◽  
Hironori Tanaka ◽  
Takahiro Tanaka ◽  
Yasuteru Fujino ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Array Analysis ◽  
Third Line ◽  
Protein Array Analysis ◽  
Third Line Treatment

AbstractBackground & AimsThe efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway by protein array analysis.MethodsWe retrospectively enrolled 57 unresectable HCC patients. Radiologic responses in 53 patients were evaluated by modified Response Evaluation Criteria in Solid Tumors. Active signal transduction pathways in cells were identified by protein array analysis, including 1205 proteins.ResultsPatients comprised 34 tyrosine kinase inhibitor (TKI)-naive (first-line), nine SOR-intolerant (second-line), and ten resistant to regorafenib (third-line). Objective response rates (ORRs) were 61.8% (21/34) in TKI-naive, 33.3% (3/9) in second-line, and 20.0% (2/10) in third-line groups. The overall survival (OS) and the progression free survival (PFS) in the first-line was significantly longer than those in third-line group (p<0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated as second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 cells (30 μM) was significantly higher than that against PLC/PRF5 cells (6.4 μM). LEN inhibited significantly more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than PLC/PRF5-R2 cells.ConclusionsLEN was active and safe as a second/third-line treatment for unresectable HCC. LEN seems to be more effective for HCC patients with better hepatic reserve function or before TKI-resistance is acquired because of partial cross-resistance to SOR.

Efficacy and safety of taxane-monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: A multicenter retrospective study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 154-154
Author(s):  
Sadayuki Kawai ◽  
Sakura Iizumi ◽  
Atsuo Takashima ◽  
Yukiya Narita ◽  
Masahiro Tajika ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
The Third ◽  
Third Line ◽  
Ecog Ps ◽  
Third Line Treatment

154 Background: While taxane-monotherapy following fluoropyrimidine plus platinum is recognized as the standard treatment strategy for advanced gastric cancer, triplet chemotherapy with docetaxel, cisplatin and S-1 (DCS) is another option for first-line therapy in Japan. However, efficacy of taxane after DCS therapy has not been sufficiently evaluated. Methods: We retrospectively evaluated the efficacy and safety of taxane-monotherapy after DCS between January 2010 and April 2015 for advanced gastric cancer. The taxane-monotherapy included weekly paclitaxel (PTX) (80 mg/m2, day 1, 8 and 15 of a 28-day cycle) and triweekly nab-PTX (260 mg/m2, day 1). Other selection criteria were: ECOG PS < 2; adequate organ function; no severe ascites; HER2-negative. Results: Thirty of 92 patients who had been treated with DCS received taxane-monotherapy. Fifteen and 15 patients received taxane-monotherapy as the second and third-line treatment, respectively. Patients characteristics of each group (2nd/3rd) were; median age: 64/62 (range 27-75/42-75); ECOG PS ≤ 1: 14/13; number of metastatic sites ≥ 2: 9/12; median taxane-free interval from first-line treatment: 1.6/3.4 (range 0.9-2.3/2.2-8.3) months; median total dose of prior DTX: 349/208 (range 39-844/141-685) mg/m2. Number of patients who received PTX/nab-PTX were 10/5 and 13/2 in the second and third line treatment. Median relative dose intensity of taxane was 96.4% (range 57.6-172.9%) in the second-line, 98.5% (44.0-166.8%) in the third-line group. Response rate and disease control rate were 0% and 37.5% in the second-line, and 0% and 38.5% in the third-line group. Median progression free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line. Grade 3 or 4 neutropenia, anemia, and anorexia, occurred in 33%, 13% and 13% in the second-line group, and 6.7%, 13% and 6.7% in the third–line group, associated with no treatment related death. Conclusions: It is suggested that taxane-monotherapy has acceptable toxicities but insufficient efficacy in advanced gastric cancer patients after DCS therapy.

scholarly journals Triggering atrial fibrillation after omalizumab injection in a patient with chronic spontaneous urticarial. A case report

2019 ◽  
Vol 92 (1) ◽  
pp. 91-93 ◽  
Author(s):  
Songul Cildag
Keyword(s):  
Atrial Fibrillation ◽  
Side Effects ◽  
Chronic Spontaneous Urticaria ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
High Efficacy ◽  
Biological Treatments ◽  
Third Line ◽  
Antiarrhythmic Treatment ◽  
Third Line Treatment

Introduction. Omalizumab is recommended as a third-line treatment in the treatment of chronic spontaneous urticaria. During omalizumab use, which has high efficacy and safety, the side effects observed are usually moderate and temporary. Here we discuss the triggering of atrial fibrillation following omalizumab injection.Case report. A 72-year-old female patient was treated with omalizumab 300 mg / day due to chronic spontaneous urticaria resistant to conventional treatments. Atrial fibrillation developed 6 hours after the second injection of omalizumab in the patient who had atrial fibrillation and who had been monitored with antiarrhythmic treatment and sinus rhythm for 1 year. The treatment was discontinued because omalizumab was thought to trigger atrial fibrillation, as no other reason to explain the triggering of atrial fibrillation could be found.Results and conclusion. There is no data in the literature on the use of omalizumab in patients with atrial fibrillation. Different side effects of biological treatments can be observed. In particular, omalizumab should be used with caution in elderly patients and patients with arrhythmia.

Third-line treatment: A randomized, double-blind, placebo-controlled phase III ALTER-0303 study—Efficacy and safety of anlotinib treatment in patients with refractory advanced NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9053-9053 ◽  
Author(s):  
Baihui Han ◽  
Kai Li ◽  
Qiming Wang ◽  
Yizhuo Zhao ◽  
Li Zhang ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Advanced Nsclc ◽  
Phase Iii ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Third Line ◽  
Ecog Ps ◽  
Third Line Treatment

9053 Background: Anlotinib hydrochloride, an oral TKI targeting VEGFR, FGFR, PDGFR and c-Kit, showed promising efficacy in PhaseⅡstudy. Here, we evaluated the efficacy and safety of anlotinib as third-line treatment for advanced NSCLC, a randomized, double-blind, placebo-controlled Phase Ⅲtrial (ALTER-0303). Methods: Eligible ⅢB/Ⅳ NSCLC pts who progressed after at least 2 lines of prior therapies were randomized 2:1 to receive anlotinib or placebo (12 mg QD from day 1 to 14 of a 21-day cycle) till progression or intolerable toxicity. Enrolled pts harboring EGFR or ALK mutations must had failed in previous match-targeted therapies. The primary endpoint is OS; secondary endpoint includes PFS, DCR and ORR. Results: As of Aug 2016, total of 437 pts from 31 sites were randomized. The baseline characteristics of Anlotinib arm (N=294) and placebo arm (N=143) were well balanced in the age, gender, ECOG PS and gene states. With 292 OS events (66.82%), significant superiorities in OS, PFS, DCR and ORR were observed in Anlotinib arm according to investigator-assessed results. Grade ≥ 3 treatment-related AEs were hypertension, dermal toxicity and hypertriglyceridemia. There was no treatment–related death in either arm. (Data presented in the Table.) Conclusions: ALTER-0303 trial met its primary endpoint. Anlotinib significantly improved OS and PFS in advanced NSCLC with a manageable safety profile. The results strongly suggest that anlotinib should be considered as a candidate for the third-line treatment or beyond in advanced NSCLC. Clinical trial information: NCT02388919. [Table: see text]

Efficacy and safety of irinotecan monotherapy as third-line treatment for advanced gastric cancer

2016 ◽  
Vol 78 (4) ◽  
pp. 809-814 ◽  
Author(s):  
Takeshi Kawakami ◽  
Nozomu Machida ◽  
Hirofumi Yasui ◽  
Masahiro Kawahira ◽  
Sadayuki Kawai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
Third Line ◽  
Third Line Treatment

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

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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