Continuous daily dosing (CDD) of sunitinib malate (SU) compares favorably with intermittent dosing in pts with advanced GIST

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10015-10015 ◽  
Author(s):  
S. George ◽  
J. Y. Blay ◽  
P. G. Casali ◽  
A. Le Cesne ◽  
J. A. Morgan ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Safety Data ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Sunitinib Malate ◽  
Phase Iii Study ◽  
Multitargeted Tyrosine Kinase Inhibitor ◽  
Dosing Strategy ◽  
To Receive ◽  
Advanced Gist

10015 Background: SU, an oral multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, RET and FLT3, is approved multinationally for the treatment of imatinib (IM)-resistant or -intolerant GIST. SU 50 mg/d on a 4/2 schedule (6-wk cycles: 4 wks on treatment, 2 wks off) has demonstrated efficacy and acceptable tolerability in pts with advanced IM-resistant GIST. The current study assesses the efficacy and safety of CDD of SU in this pt population. Methods: In this multicenter phase (ph) II trial, pts with IM-resistant/intolerant GIST were randomized to receive morning or evening dosing of SU 37.5 mg daily. The primary endpoint was clinical benefit rate (CBR; percentage of pts with confirmed CR, PR or SD for =24 wks per RECIST). Investigator-assessed efficacy and safety data compiled in this ph II study and an earlier ph III study were compared informally, and the PK of SU and its metabolite were also analyzed. Results: Of 61 pts randomized, 60 received treatment with SU (30 pts/arm; ITT population). At a median duration on study of 30 wks (range: 4–52+), 33 pts remain on study and 27 have discontinued. The SU dose was reduced to 25 mg/d in 9 pts due to AEs. The most common non-hematologic AEs of any cause (primarily grade [gr] 1/2) were diarrhea (40%), asthenia (38%) and fatigue (35%). Gr 3 AEs were asthenia (13%), fatigue (7%) and diarrhea (7%); gr 4 abdominal pain was reported in 3% pts. Hematologic toxicities included gr 3 anemia (10%), neutropenia (17%, all non-febrile) and thrombocytopenia (7%) and gr 4 anemia (3%). Toxicities were similar in the morning and evening dosing groups. Preliminary PK data indicated no unexpected accumulation with CDD. To date, median PFS is 27 wks (CI: 24–41) and overall CBR is 24%, including 11% pts with PRs, which compares favorably with results obtained with the approved regimen of SU 50 mg/d on the 4/2 schedule (N=207; PR: 7%; CBR: 25%; PFS 28 wks [CI: 14–34]; phase III study). Conclusions: SU is well tolerated and clinically active when given as 37.5 mg CDD in pts with IM- resistant/-intolerant GIST. The AE profile for SU CDD appears similar to that of the 4/2 schedule. Morning and evening dosing seem to have similar tolerability. SU CDD appears to be a safe and effective alternative dosing strategy for pts with IM-resistant/intolerant GIST. No significant financial relationships to disclose.

Efficacy and safety of BCD-017, a novel pegylated filgrastim: Results of open-label controlled phase II study in patients with breast cancer receiving myelosuppressive chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20593-e20593 ◽  
Author(s):  
Olga V. Salafet ◽  
Tatiana V. Chernovskaya ◽  
Ludmila P. Sheveleva ◽  
Andrey V. Khorinko ◽  
Tatiana I. Prokopenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Group A ◽  
Phase Iii Study ◽  
Study Support ◽  
To Receive

e20593 Background: Pegfilgrastim (conjugate of filgrastim and 20 kDa polyethylene glycol (PEG) is approved for treatment of chemotherapy-associated neutropenia. BCD-017 (empegfilgrastim) is a covalent conjugate of filgrastim with 30 kDa PEG. Increased molecular weight of PEG molecule may provide additional benefits compared to pegfilgrastim. Methods: To compare efficacy and safety of filgrastim and BCD-017 at 3 mg and 6 mg doses an open-label, randomized, active-comparator, non-inferiority trial was conducted. 60 patients with histologically or cytologically confirmed breast cancer were randomly assigned to receive either subcutaneous (s.c.) injection of 3 mg BCD-017 (n=21), 6 mg BCD-017 (n = 20), or 5 mg/kg s.c. injections of filgrastim (n=19) administered daily until ANC ≥ 10x109 cells/L (maximum of 14 days) after chemotherapy (doxorubicin 60 mg/m2 and docetaxel 75 mg/m2) with stratification for weight and prior chemotherapy exposure. The primary efficacy endpoint was the incidence of severe neutropenia (ANC < 1.0x109 cells/L) during the first cycle of chemotherapy. Results: Incidence of severe neutropenia during the first chemotherapy cycle was 85,7%, 65,0% and 61,1% in BCD-017 3 mg, BCD-017 6 mg and filgrastim groups, respectively. Differences between BCD-017 groups and filgrastim group were not significant. Mean duration of grade 4 neutropenia in cycle 1 was 0,43, 0,40 and 0,33 days, accordingly (95% CI for difference between BCD-017 3 mg and filgrastim groups -0.22 to 0.41; 95% CI for difference between BCD-017 6 mg and filgrastim groups -0.25 to 0.38). Febrile neutropenia was observed only in BCD-017 3 mg and BCD-017 6 mg groups (one case in each group). A single administration of BCD-017 at the doses of 3 mg and 6 mg was as safe and well tolerated as standard daily filgrastim administration. There were no unexpected adverse events in all groups. Conclusions: The results of this study support comparable efficacy of single s.c. injection of 6 mg BCD-017 versus daily 5 mg/kg s.c. injections of filgrastim. Further phase III study of BCD-017 for treatment and prophylaxis of neutropenia in patients receiving chemotherapy is necessary. Clinical trial information: NCT01569087.

scholarly journals Final Results of a Randomized, Phase III Study of Rituximab With or Without Idelalisib Followed by Open-Label Idelalisib in Patients With Relapsed Chronic Lymphocytic Leukemia

2019 ◽  
Vol 37 (16) ◽  
pp. 1391-1402 ◽  
Author(s):  
Jeff P. Sharman ◽  
Steven E. Coutre ◽  
Richard R. Furman ◽  
Bruce D. Cheson ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Extension Study ◽  
Efficacy And Safety ◽  
Term Efficacy ◽  
Phase Iii Study ◽  
Grade 3 ◽  
To Receive

PURPOSE A randomized, double-blind, phase III study of idelalisib (IDELA) plus rituximab versus placebo plus rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) was terminated early because of superior efficacy of the IDELA-plus-rituximab (IDELA/R) arm. Patients in either arm could then enroll in an extension study to receive IDELA monotherapy. Here, we report the long-term efficacy and safety data for IDELA-treated patients across the primary and extension studies. PATIENTS AND METHODS Patients were randomly assigned to receive rituximab in combination with either IDELA 150 mg twice daily (IDELA/R; n = 110) or placebo (placebo/R; n = 110). Key end points were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety. RESULTS The long-term efficacy and safety of treatment with IDELA was assessed in 110 patients who received at least one dose of IDELA in the primary study, 75 of whom enrolled in the extension study. The IDELA/R-to-IDELA group had a median PFS of 20.3 months (95% CI, 17.3 to 26.3 months) after a median follow-up time of 18 months (range, 0.3 to 67.6 months). The ORR was 85.5% (94 of 110 patients; n = 1 complete response). The median OS was 40.6 months (95% CI, 28.5 to 57.3 months) and 34.6 months (95% CI, 16.0 months to not reached) for patients randomly assigned to the IDELA/R and placebo/R groups, respectively. Prolonged exposure to IDELA increased the incidence of all-grade, grade 2, and grade 3 or greater diarrhea (46.4%, 17.3%, and 16.4%, respectively), all-grade and grade 3 or greater colitis (10.9% and 8.2%, respectively) and all-grade and grade 3 or greater pneumonitis (10.0% and 6.4%, respectively) but did not increase the incidence of elevated hepatic aminotransferases. CONCLUSION IDELA improved PFS and OS compared with rituximab alone in patients with relapsed CLL. Long-term IDELA was effective and had an expected safety profile. No new IDELA-related adverse events were identified with longer exposure.

Efficacy and safety data from patients with advanced renal cell cancer treated with tivozanib hydrochloride after progression on sorafenib.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 364-364
Author(s):  
Robert John Motzer ◽  
Dmitry Nosov ◽  
Piotr Tomczak ◽  
Anna Berkenblit ◽  
Brooke Esteves ◽  
...  
Keyword(s):  
Median Duration ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Safety Data ◽  
Phase Iii ◽  
Extension Study ◽  
Efficacy And Safety

364 Background: Tivozanib hydrochloride (tivozanib) is a potent, selective, tyrosine kinase inhibitor of all three vascular endothelial growth factor receptors, with a long half-life and has shown superior efficacy, measured as progression-free survival (PFS), as first-line, targeted therapy vs. sorafenib in a phase III trial (TIVO-1) in patients with advanced renal cell carcinoma (J Clin Oncol2012;30[suppl]:Abstract 4501). Patients who progressed (PD) on sorafenib could receive tivozanib in an open-label, prospective multicenter extension study of TIVO-1. We report preliminary efficacy and safety data for patients who had PD on sorafenib and subsequently received tivozanib in this extension study. Methods: Patients with PD on sorafenib, per RECIST version 1.0, were eligible to receive tivozanib dosed at 1.5 mg/day PO for 3 weeks followed by a 1-week rest, in repeated 4-week cycles, until PD or unacceptable toxicity. Patients were to have been no more than 4 weeks from last dose of sorafenib until initiation of tivozanib, and have an ECOG performance status of ≤2. Dose adjustments were performed as previously reported. Objectives included assessing objective response rate (ORR), duration of response, PFS for tivozanib following PD on sorafenib, and overall survival. Results: As of January 20, 2012, 127 patients (72.4% male) were evaluable for response. Median age was 59.0 years (range: 23–85 years). ORR was 7.9% (95% CI 3.8–14.0%; partial response [PR]=7.9%; stable disease [SD]=65.4%; PD=18.9%), and 71.3% of patients showed tumor shrinkage. Median duration of PR was 11.1 months (95% CI ≥7.5 months). Median duration of SD was 12.7 months (95% CI ≥7.4 months). Median PFS was 5.6 months (95% CI 5.4–9.1 months). Median OS was not yet reached. Most commonly reported treatment-emergent adverse events (all grades/Grade ≥3) were hypertension (22.4%/10.2%), asthenia (11.0%/3.1%), fatigue (11.0%/3.9%), palmar-plantar erythrodysesthesia (11.0%/1.6%), and diarrhea (10.2%/1.6%). Conclusions: Tivozanib has anti-tumor activity after PD on sorafenib. The adverse-event profile of tivozanib after sorafenib is similar to that observed in TIVO-1. Clinical trial information: NCT01076010.

Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 510-510 ◽  
Author(s):  
Justin Stebbing ◽  
Yauheni Valerievich Baranau ◽  
Valery Baryash ◽  
Alexey Manikhas ◽  
Vladimir Moiseyenko ◽  
...  
Keyword(s):  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
To Receive ◽  
Related Reaction

510 Background: CT-P6 (C) is a proposed biosimilar to trastuzumab. This trial (NCT02162667) evaluated the similarity of C and trastuzumab in efficacy and safety for HER2+ EBC. Methods: 549 patients with HER2+ EBC were randomized to receive C (n=271) or trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (Cycles 5-8). C or trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints were overall response rate (ORR), PK, PD and safety. After surgery, patients received adjuvant C or trastuzumab to complete a total of 1-year treatment. Results: The pCR rate was 46.8% for C and 50.4% for trastuzumab. The 95% CIs for the risk ratio estimate were within the equivalence margin (0.74, 1.35) in PPS and ITT analyses. Other efficacy endpoints were similar between C and trastuzumab. The proportion of patients with at least 1 treatment-emergent SAE was 6.6% for C and 7.6% for trastuzumab. Only 1 patient in each group withdrew treatment due to significant LVEF decrease. Infusion-related reaction was reported for 8.5% of patients in C and 9.0% of patients in trastuzumab. Conclusions: This study demonstrated the similarity of efficacy in terms of pCR between CT-P6 and trastuzumab in EBC patients. Secondary efficacy endpoints also supported the similarity between CT-P6 and trastuzumab. CT-P6 was well tolerated with a similar safety profile to that of trastuzumab during the neoadjuvant period. Clinical trial information: NCT02162667. [Table: see text]

Final efficacy and safety results of pemetrexed (pem) continuation maintenance (mtc) therapy in the elderly from the PARAMOUNT phase III study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8068-8068
Author(s):  
Cesare Gridelli ◽  
Michael Thomas ◽  
Kumar Prabhash ◽  
Claude El Kouri ◽  
Fiona Helen Blackhall ◽  
...  
Keyword(s):  
Safety Data ◽  
Dose Intensity ◽  
The Elderly ◽  
Phase Iii ◽  
Double Blind Study ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Phase Iii Study ◽  
Continuation Maintenance ◽  
To Receive

8068 Background: The PARAMOUNT phase III trial showed that mtc pem after pem-cisplatin induction was well tolerated and effective for patients (pts) with advanced nonsquamous NSCLC. Here we present the final OS and safety data from this study in elderly (≥70 yrs) vs. non-elderly (<70 yrs) pts. Methods: In this double-blind study, 539 pts with a PS of 0/1 were randomized (2:1, stratified for stage, PS and induction response) to receive mtc pem (n=359, 500 mg/m2, day 1, 21 day cycle) or placebo (plc) (n=180). The study was powered for PFS (previously reported) and key secondary OS. Subgroup analyses were done for pts ≥70 yrs and <70 yrs. Results: Subgroups (≥70: n=92, 17%; <70: n=447, 83%) had similar baseline characteristics except for PS and sex (elderly, PS 0/1: 22%/77%, M/F: 66%/34%; non-elderly, PS 0/1: 34%/65%, M/F: 56%/44%). The median ages were 73 yrs (≥70) and 60 yrs (<70). The mean cycles received for pts ≥70 were 7.4 (range 1-36, dose intensity (DI) 91%) for pem and 4.5 for plc, and for pts <70 were 8.0 (range 1-44, DI 94%) for pem and 5.1 for plc. The OS HRs (pem vs. plc) were 0.89 (95% CI: 0.55-1.4) for ≥70 yrs and 0.75 (95% CI: 0.60-0.95, p=0.015) for<70 yrs. The median OS (95% CI) (≥70) was 13.7 mo (10.4-19.4) for pem and 12.1 mo (8.4-16.9) for plc; the median OS (95%CI) (<70) was 13.9 mo (12.5-16.1) for pem and 10.8 mo (9.5-12.9) for plc. The 1 and 2 yr OS rates (95% CI) for the elderly were 60% (45-71%) and 34% (21-47%) for pem vs. 52% (36-66%) and 28% (15-43%) for plc, respectively. For non-elderly pts, the 1 and 2 yr OS rates were 58% (52-63%) and 31% (26-37%) for pem vs. 43% (35-52%) and 19% (13-27%) for plc, respectively. The Table shows a subset of drug-related AEs. Conclusions: Continuation mtc pem had comparable survival and toxicity profiles in the ≥70 and <70 yrs subgroups. However, Gr 3/4 anemia and neutropenia were numerically higher for pts ≥70 yrs. Clinical trial information: NCT00789373. [Table: see text]

Subgroup analysis of crizotinib versus either pemetrexed (PEM) or docetaxel (DOC) in the phase III study (PROFILE 1007) of advanced ALK-positive non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8105-8105
Author(s):  
Benjamin J. Solomon ◽  
Scott N. Gettinger ◽  
Gregory J. Riely ◽  
Shirish M. Gadgeel ◽  
Hiroshi Nokihara ◽  
...  
Keyword(s):  
Risk Ratio ◽  
Standard Of Care ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Vision Disorder ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Alk Positive ◽  
To Receive ◽  
Clinical Trial Information

8105 Background: PROFILE 1007 compared the efficacy and safety of crizotinib with that of standard-of-care chemotherapy in patients with ALK+ NSCLC. Although the study was not designed for formal assessment of patient outcomes on crizotinib vs. PEM or crizotinib vs. DOC, due to later interest, we performed retrospective efficacy and safety analyses of patient subgroups treated with crizotinib or each chemotherapy individually. Methods: Patients with stage IIIB/IV ALK+ NSCLC previously treated with 1 prior platinum-based regimen were randomized to receive crizotinib 250 mg PO BID or chemotherapy (PEM 500 mg/m2 or DOC 75 mg/m2, IV q3 wk). Patients with progressive disease on chemotherapy were offered crizotinib treatment in a separate study. In these subgroup analyses, PFS and ORR based on independent radiologic review, and safety were evaluated. Results: Of 347 patients randomized, 172 received crizotinib, 99 PEM, 72 DOC, and 4 no treatment. At data cutoff (Mar 2012), 85 crizotinib patients, 21 PEM patients, and 7 DOC patients were receiving treatment. Median treatment duration was longer in the crizotinib arm (7.1 mo) than in either the PEM (4.1 mo) or DOC (2.1 mo) treatment subgroups. Median PFS was significantly longer on crizotinib (7.7 mo) than on either PEM (4.2 mo; HR, 0.59; P=0.0004) or DOC (2.6 mo; HR, 0.30; P<0.0001). 1-year PFS rates were 31% on crizotinib, 16% on PEM, and 6% on DOC. The ORR on crizotinib (66%) was significantly higher than on either PEM (29%; risk ratio, 2.31; P<0.0001) or DOC (7%; risk ratio, 9.65; P<0.0001). The most common all-causality adverse events with crizotinib were diarrhea (60%), vision disorder (60%), and nausea (55%); with PEM, nausea (38%), fatigue (36%), and decreased appetite (26%); and with DOC, alopecia (47%), neutropenia (43%), and nausea (36%). Conclusions: Crizotinib’s superior efficacy over chemotherapy, with a distinct but generally tolerable and manageable side effect profile in patients with advanced ALK+ NSCLC, was also observed in separate comparisons with either PEM or DOC. In patients receiving chemotherapy, median PFS, 1-year PFS rates, and ORR were all numerically higher on PEM than on DOC. Clinical trial information: NCT00932893.

scholarly journals Ripretinib (DCC-2618): a new tyrosine kinase inhibitor for the treatment of metastatic gastrointestinal stromal tumors

2020 ◽  
Vol 25 (1) ◽  
pp. 4-8
Author(s):  
D.. A Filonenko ◽  
T. E. Tikhomirova ◽  
A. A. Meshcheryakov
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitor ◽  
Phase Iii ◽  
Stromal Tumors ◽  
Phase Iii Study ◽  
Approved Drugs ◽  
Advanced Gist ◽  
Experienced Treatment

Ripretinib (DCC-2618) is a novel tyrosine kinase inhibitor designed to broadly inhibit primary and secondary mutations in KIT (exons 9,11, 13, 14,17,18) and PDGFRA (exon 18). Here in our article we describe clinical trials of ripretinib for patient with advanced gastrointestinal stromal tumors (GIST). The clinical trial INVICTUS-randomized phase III study of ripretinib for patient with advanced GIST in 4 lines therapy; it is the most important results, because there are currently no approved drugs for such patients. Median PFS was significantly improved with ripretinib compared with placebo 6,3 и 1 months (p0,0001) and median OS was significantly improved with ripretinib compared with placebo 15,1 и 6,6 months (p0,004). High efficacy of ripretinib was accompanied with favorable profile of toxicity, only 8,2% patients experienced treatment discontinuations due to adverse events.

scholarly journals FRESCO-2: a global Phase III study investigating the efficacy and safety of fruquintinib in metastatic colorectal cancer

2021 ◽  
Author(s):  
Arvind Dasari ◽  
Alberto Sobrero ◽  
James Yao ◽  
Takayuki Yoshino ◽  
William Schelman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Supportive Care ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Phase Iii Study

Fruquintinib, a novel, highly selective, small-molecule tyrosine kinase inhibitor of VEGF receptors (VEGFRs)-1, -2 and -3, is approved in China for the treatment of metastatic colorectal cancer. FRESCO-2, a global, randomized, double-blind, placebo-controlled, Phase III study, is investigating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Key inclusion criteria include: progression on or intolerance to TAS-102 and/or regorafenib; and prior treatment with approved chemotherapy, anti-VEGF therapy, and, if RAS wild-type, anti-EGFR therapy. Approximately 687 patients will be randomized 2:1 to fruquintinib plus best supportive care or placebo plus best supportive care. Primary and key secondary end points are overall survival and progression-free survival, respectively. FRESCO-2 is enrolling in the USA, Europe, Australia and Japan.

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