Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial

Komatsu, Yoshito; Doi, Toshihiko; Sawaki, Akira; Kanda, Tatsuo; Yamada, Yasuhide; Kuss, Iris; Demetri, George D.; Nishida, Toshirou

doi:10.1007/s10147-015-0790-y

Cited by 32 publications

(34 citation statements)

References 19 publications

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“…However, it was previously reported that the incidence of hypothyroidism with axitinib treatment alone was also higher in Japanese patients than the overall population in the studies of single‐agent axitinib in patients with advanced RCC . The trend of higher frequency of hypothyroidism in Japanese patients compared to the overall population was observed with other VEGFR inhibitors, such as sorafenib and regorafenib . In addition, immune‐related thyroid disorders observed in Japanese patients did not require corticosteroid therapy.…”

Section: Discussionmentioning

confidence: 93%

“…14,19 The trend of higher frequency of hypothyroidism in Japanese patients compared to the overall population was observed with other VEGFR inhibitors, such as sorafenib and regorafenib. 14,35 In addition, immune-related thyroid disorders observed in Japanese patients did not require corticosteroid therapy. The incidence of other immune-related adverse events such as hepatitis, colitis, adrenal insufficiency or rash was similar between Japanese patients and the overall population.…”

Section: Discussionmentioning

confidence: 99%

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Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

et al. 2020

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The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment‐naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression‐free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD‐L1+ tumors (≥1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval [CI]) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (hazard ratio [HR], 0.49; 95% CI, 0.152, 1.563) in patients with PD‐L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD‐L1 expression. Median overall survival (OS) has not been reached in either arm in patients with PD‐L1+ tumors and irrespective of PD‐L1 expression. ORR (95% CI) was 60.6% (42.1%, 77.1%) vs 17.6% (6.8%, 34.5%) in patients irrespective of PD‐L1 expression. Common treatment‐emergent adverse events (all grade; grade ≥3) in each arm were hand‐foot syndrome (64%; 9% vs 71%; 9%), hypertension (55%; 30% vs 44%; 18%), hypothyroidism (55%; 0% vs 24%; 0%), dysgeusia (21%; 0% vs 56%; 0%) and platelet count decreased (3%; 0% vs 65%; 32%). Avelumab + axitinib was efficacious and tolerable in treatment‐naive Japanese patients with advanced RCC, which is consistent with results in the overall population.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

et al. 2020

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“…Unfortunately, many GIST patients fail to receive clinical benefit from sunitinib. This resulted in the recent approval of regorafenib by the FDA as a third-line agent for the treatment of patients with GIST refractory to IM and sunitinib [48]. Regorafenib is a broad inhibitor of receptor tyrosine kinases that targets KIT, PDGFRA/B, RET, RAF1, BRAF, vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor [49].…”

Section: Introductionmentioning

confidence: 99%

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Alturkmani

Pessetto

Godwin

2015

Expert Opinion on Investigational Drugs

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Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival.

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“…HFSR was the toxicity observed most frequently and the most common reason for dose reduction in the present study. The incidence of HFSR in the study population (82%) was higher than that in the regorafenib group in the GRID trial (56%) [12] but was similar to that in the regorafenib group in the GRID trial Japanese subgroup (92%) [13]. The toxicity was managed successfully with a dose reduction.…”

Section: Discussionmentioning

confidence: 56%

Efficacy and safety of regorafenib in Korean patients with advanced gastrointestinal stromal tumor after failure of imatinib and sunitinib: A multicenter study based on the management access program.

Son¹,

Ryu²,

Park³

et al. 2015

JCO

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Original ArticlePurpose The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients. Materials and MethodsFifty-seven Korean patients with advanced GIST who experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on /1 week off). ResultsNone of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for  12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a handfoot skin reaction (n=31). ConclusionThis study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.

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Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial

Cited by 32 publications

References 19 publications

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Efficacy and safety of regorafenib in Korean patients with advanced gastrointestinal stromal tumor after failure of imatinib and sunitinib: A multicenter study based on the management access program.

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