scholarly journals Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study

2021 ◽  
Author(s):  
John R. Zalcberg ◽  
Michael C. Heinrich ◽  
Suzanne George ◽  
Sebastian Bauer ◽  
Patrick Schöffski ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Disease Progression ◽  
Dose Escalation ◽  
Clinical Benefit ◽  
Stromal Tumor

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.

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 Avapritinib in advanced gastrointestinal stromal tumor: case series and review of the literature from a tertiary care center in India

2021 ◽  
pp. FSO676
Author(s):  
Saurav Verma ◽  
Rohit Reddy ◽  
Sheragaru Hanumanthappa Chandrashekhara ◽  
Shamim Ahmed Shamim ◽  
Sarthak Tripathy ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Clinical Benefit ◽  
Care Center ◽  
Tertiary Care ◽  
Case Series ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Stromal Tumor ◽  
Significant Difference ◽  
Us Fda

The therapeutic landscape in advanced gastrointestinal stromal tumor has evolved. Avapritinib and ripretinib have now been approved by the US FDA for platelet-derived growth factor alpha D842V-mutant and refractory gastrointestinal stromal tumor patients, respectively. Here we report five patients who have been on avapritinib under an expanded access program. Response assessment was available for four patients – a partial response in two patients and stable disease in one, while one patient had progressive disease. Though preliminary results of the VOYAGER trial have shown less activity of avapritinib and no significant difference in progression-free survival when compared with regorafenib, avapritinib may show some clinical benefit in a subset of patients refractory to approved therapies. We share our experience of five cases, with clinical benefit in three. We believe avapritinib should be further evaluated in clinical trials.

Real world treatment patterns of gastrointestinal stromal tumor patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15602-e15602
Author(s):  
J. A. Morgan ◽  
A. Guo ◽  
D. Williams ◽  
A. Guérin ◽  
D. Latremouille-Viau ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Dose Escalation ◽  
Real World ◽  
Kinase Inhibitor ◽  
Treatment Patterns ◽  
Stromal Tumor ◽  
Data Availability ◽  
Dose Increase ◽  
First Line ◽  
Long Term Treatment

e15602 Background: Imatinib is accepted as the standard first-line therapy to treat gastrointestinal stromal tumor (GIST) in patients with unresectable or metastatic disease. In the case of disease progression, physicians may consider increasing imatinib dose or switching to another second-line agent, such as sunitinib. The aim of this study was to analyze the real-world long term treatment patterns of GIST patients. Methods: Two large claims databases from 01/1999 to 03/2008 were combined (MarketScan and Ingenix Impact) to extract patients diagnosed with GIST who initiated on imatinib ≥400 mg/day. Patients were followed from the first observed imatinib prescription to the end of data availability. Patients who dose increased during the study period were defined as dose escalators, while patients who later switched to sunitinib with or without dose escalation were defined as switchers. Kaplan Meier analyses were used to estimate the rate of treatment changes over time including imatinib discontinuation, defined as a lack of imatinib supply for ≥60 days, and switching back to initial treatment. Results: Among the 1,508 GIST patients who initiated on imatinib, 253 patients had a dose increase and 153 patients switched to sunitinib during the study period. 20.1% patients on imatinib discontinued by the end of the first year, and 43.0% discontinued by the end of the third year. Among the 153 switchers, 61 patients had a dose escalation prior to the switch, of which 82.0% reached 800 mg before switching. Among all the switchers, 20.3% switched back to imatinib within 6 months. Conclusions: These claims-based findings on the duration of first-line imatinib therapy of GIST patients supports data on imatinib efficacy in treating GIST from formal clinical research studies. Most of GIST patients who initiated imatinib continued on this therapy without undergoing dose increase or switch to sunitinib. Among switchers, most did not dose escalate before switching and many eventually switched back to imatinib. It appears that physicians tend to not always follow clinical practice guidelines developed based on expert consensus, with respect to decision rules for dose escalation, or for the appropriate time to change kinase inhibitor therapy. [Table: see text]

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