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Benefit of pazopanib in advanced gastrointestinal stromal tumours: results from a phase II trial (SSG XXI, PAGIST)

Eriksson, Mikael LU orcid ; Reichardt, P. ; Joensuu, H ; Krarup-Hansen, A. ; Hagberg, Oskar LU ; Hohenberger, P. ; Hagberg, H ; Hansson, L ; Foukakis, Theodoros and Pulkkanen, K. , et al. (2021) In ESMO Open 6(4).
Abstract
BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized,... (More)
BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
ESMO Open
volume
6
issue
4
publisher
BMJ Publishing Group
external identifiers
  • scopus:85117623106
  • pmid:34271307
ISSN
2059-7029
DOI
10.1016/j.esmoop.2021.100217
language
English
LU publication?
yes
id
49677f24-9e59-4901-b5d7-78836dda6259
date added to LUP
2021-11-22 12:44:20
date last changed
2022-05-12 23:59:20
@article{49677f24-9e59-4901-b5d7-78836dda6259,
  abstract     = {{BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.}},
  author       = {{Eriksson, Mikael and Reichardt, P. and Joensuu, H and Krarup-Hansen, A. and Hagberg, Oskar and Hohenberger, P. and Hagberg, H and Hansson, L and Foukakis, Theodoros and Pulkkanen, K. and Bauer, S. and Goplen, Dorota and Blach-Rossen, P. and Sundby Hall, Kirsten}},
  issn         = {{2059-7029}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{ESMO Open}},
  title        = {{Benefit of pazopanib in advanced gastrointestinal stromal tumours: results from a phase II trial (SSG XXI, PAGIST)}},
  url          = {{http://dx.doi.org/10.1016/j.esmoop.2021.100217}},
  doi          = {{10.1016/j.esmoop.2021.100217}},
  volume       = {{6}},
  year         = {{2021}},
}