scholarly journals Dose escalation of ripretinib can lead to response in advanced gastrointestinal stromal tumor patients refractory to the standard dose: a report of two cases

2021 ◽  
Vol 4 ◽  
pp. 1-1
Author(s):  
Philippos Apolinario Costa ◽  
Caroline Kamal Abdelmessih Hana ◽  
Navin Chakravarthy Balaji ◽  
Anthony Frank Skryd ◽  
Brianna Nicole Valdes ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Dose Escalation ◽  
Standard Dose ◽  
Stromal Tumor ◽  
Tumor Patients

Targeted therapy in gastrointestinal stromal tumor (GIST): A nationwide database analysis from Taiwan.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 437-437
Author(s):  
I-Jen Chiang ◽  
Wen-Yi Shau ◽  
Wei-Tse Fang ◽  
Chi-Hui Fang ◽  
Yen-Yang Chen
Keyword(s):  
Targeted Therapy ◽  
Gastrointestinal Stromal Tumor ◽  
Dose Escalation ◽  
Targeted Therapies ◽  
Standard Dose ◽  
Stromal Tumor ◽  
Treatment Modalities ◽  
Research Database ◽  
Line Treatment ◽  
First Line

437 Background: Gastrointestinal stromal tumor (GIST) is a visceral sarcoma that arises from the gastrointestinal tract. Currently, imatinib (first-line) and sunitinib (second-line) are two reimbursed targeted therapies for GIST in Taiwan. This study aimed to evaluate the real world data of targeted therapies in GIST treatment among Taiwanese population. Methods: We conducted a nationwide retrospective cohort study based on data from the National Health Insurance Research Database (NHIRD) between January 2005 and December 2010. NHIRD is a comprehensive database of administrative and claim data which covers over 99% of entire population in Taiwan. Patients were selected with ICD codes and targeted therapy utilization, imatinib (IMA) or sunitinib (SUN). Time to treatment discontinuation (DC) due to any reasons (such as death, intolerance and disease progression) was estimated using Kaplan-Meier analysis. Results: From 2005 to 2010, the incidence rate of GIST in Taiwan was between 20 and 30 cases per million. A total of 3,436 GIST patients were identified; the mean age was 63.2 years and 57 % were male. Most patients (94.7%) received standard dose IMA (…400mg/day). Among these patients, 136 patients (4.0%) required IMA dose escalation and 44 (1.3%) patients switched to SUN after IMA. The probability of the 1st-line treatment DC was 20%, 30.7%, 38.9%, 43.2%, and 47.1% for years 1 to 5, respectively. The probability of a change in treatment pattern (defined as either IMA dose escalation or switch to SUN) was 4% 6.8%, 9.6%, 10.5% and 11.7% for years 1 to 5. Lastly, the probability of the 2nd-line treatment DC was 20.5%, 33.7%, 41.1%, 44.8%, 51.7% for years 1 to 5, respectively. Conclusions: First-line IMA plus other treatment modalities may provide additional benefits to progression-free survival. Taiwanese GIST patients who failed first-line treatment still gained benefit from either IMA dose escalation or a switch to SUN. Additional analysis is required for the detailed comparison in different treatment patterns.

scholarly journals Effect of Gastrointestinal Bleeding on Gastrointestinal Stromal Tumor Patients: A Retrospective Cohort Study

2018 ◽  
Vol 24 ◽  
pp. 363-369 ◽  
Author(s):  
Yuqian Huang ◽  
Rui Zhao ◽  
Yaping Cui ◽  
Yong Wang ◽  
Lin Xia ◽  
...  
Keyword(s):  
Cohort Study ◽  
Gastrointestinal Bleeding ◽  
Gastrointestinal Stromal Tumor ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Stromal Tumor ◽  
Tumor Patients

scholarly journals Therapeutic Consequences from Molecular Biology for Gastrointestinal Stromal Tumor Patients Affected by Neurofibromatosis Type 1

2008 ◽  
Vol 14 (14) ◽  
pp. 4550-4555 ◽  
Author(s):  
Chiara Mussi ◽  
Hans-Ulrich Schildhaus ◽  
Alessandro Gronchi ◽  
Eva Wardelmann ◽  
Peter Hohenberger
Keyword(s):  
Molecular Biology ◽  
Gastrointestinal Stromal Tumor ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Stromal Tumor ◽  
Tumor Patients ◽  
Therapeutic Consequences

scholarly journals Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib

2020 ◽  
Vol 38 (28) ◽  
pp. 3294-3303 ◽  
Author(s):  
Filip Janku ◽  
Albiruni R. Abdul Razak ◽  
Ping Chi ◽  
Michael C. Heinrich ◽  
Margaret von Mehren ◽  
...  
Keyword(s):  
Phase I ◽  
Gastrointestinal Stromal Tumor ◽  
Dose Escalation ◽  
Phase I Study ◽  
Stromal Tumor ◽  
Second Line ◽  
Once Daily ◽  
Switch Control ◽  
Wide Range ◽  
Advanced Gist

PURPOSE In advanced gastrointestinal stromal tumor (GIST), there is an unmet need for therapies that target both primary and secondary mutations of pathogenic KIT/PDGFRA oncoproteins. Ripretinib is a novel switch-control kinase inhibitor designed to inhibit a wide range of KIT and PDGFRA mutations. PATIENTS AND METHODS This first-in-human, to our knowledge, phase I study of ripretinib (ClinicalTrials.gov identifier: NCT02571036) included a dose-escalation phase and subsequent expansion phase at the recommended phase II dose (RP2D). Eligible patients included those with advanced GIST, intolerant to or experienced progression on ≥ 1 line of systemic therapy, and other advanced malignancies. Safety, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), and preliminary antitumor activity were evaluated. RESULTS At data cutoff (August 31, 2019), 258 patients (n = 184 GIST) were enrolled, with 68 patients in the dose-escalation phase. Three DLTs were reported: grade 3 lipase increase (n = 2; 100 mg and 200 mg twice a day) and grade 4 increased creatine phosphokinase (n = 1; 150 mg once daily). MTD was not reached (maximum dose evaluated, 200 mg twice a day); 150 mg once daily was established as the RP2D. The most frequent (> 30%) treatment-emergent adverse events in patients with GIST receiving ripretinib 150 mg once daily (n = 142) were alopecia (n = 88 [62.0%]), fatigue (n = 78 [54.9%]), myalgia (n = 69 [48.6%]), nausea (n = 65 [45.8%]), palmar-plantar erythrodysesthesia (n = 62 [43.7%]), constipation (n = 56 [39.4%]), decreased appetite (n = 48 [33.8%]), and diarrhea (n = 47 [33.1%]). Objective response rate (confirmed) of 11.3% (n = 16/142) ranging from 7.2% (n = 6/83; fourth line or greater) to 19.4% (n = 6/31; second line) and median progression-free survival ranging from 5.5 months (fourth line or greater) to 10.7 months (second line), on the basis of investigator assessment, were observed. CONCLUSION Ripretinib is a well-tolerated, novel inhibitor of KIT and PDGFRA mutant kinases with promising activity in patients with refractory advanced GIST.

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