Abstract | BACKGROUND: PATIENTS AND METHODS: This single-center, single-arm, phase IIb study (NCT02465502) enrolled adults with mCRC whose disease had progressed on, or who were intolerant to, standard therapy, but who were antiangiogenic therapy-naïve. Patients received regorafenib 160 mg once daily for 3 weeks per 4-week cycle. The primary endpoint was progression-free survival (PFS) rate at week 8. RESULTS: Of 59 treated patients, almost half had received at least four prior lines of therapy. Patients received a median of 86% of the planned dose. The week 8 PFS rate was 53% (95% confidence interval [CI], 39.1-64.3); median PFS was 3.5 months (95% CI, 1.8-3.6). Median OS was 7.4 months (95% CI, 5.3-8.9). Tumor response (RECIST version 1.1) was 2%, and metabolic response rate (criteria from the European Organisation for Research and Treatment of Cancer) was 41%. The most frequently reported regorafenib-related grade ≥3 adverse events were hypertension (36%), hand-foot skin reaction (HFSR, 25%), and hypophosphatemia (24%). There were no regorafenib-related deaths. An exploratory analysis showed that patients with grade ≥2 HFSR had longer OS (10.2 months) with regorafenib treatment versus those with grades 0-1 (5.4 months). CONCLUSION: These findings support the antitumor activity of regorafenib in antiangiogenic-naïve patients with chemotherapy-refractory mCRC. IMPLICATIONS FOR PRACTICE: The multikinase inhibitor regorafenib improved overall survival in the phase III CORRECT and CONCUR trials in heavily pretreated patients with treatment-refractory metastatic colorectal cancer (mCRC). Exploratory subgroup analysis from CONCUR suggested that regorafenib treatment prior to targeted therapy (including bevacizumab) may improve outcomes. In this single-center, single-arm phase IIb study, regorafenib demonstrated antitumor activity in 59 antiangiogenic-naïve patients with chemotherapy-refractory mCRC. Further studies should assess the efficacy of regorafenib in this patient population, as well as explore the reasons behind improved outcomes among patients who had a metabolic response and those who developed hand-foot skin reaction.
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Authors | Rachel P Riechelmann, Luiz S Leite, Giovanni M Bariani, Joao Glasberg, Thomas G Rivelli, Leonardo Gomes da Fonseca, Daniela R Nebuloni, Maria I Braghiroli, Marcelo A Queiroz, Alice M Isejima, Christian Kappeler, Luciana Kikuchi, Paulo M Hoff |
Journal | The oncologist
(Oncologist)
Vol. 24
Issue 9
Pg. 1180-1187
(09 2019)
ISSN: 1549-490X [Electronic] England |
PMID | 31175167
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © AlphaMed Press 2019. |
Chemical References |
- Angiogenesis Inhibitors
- Phenylurea Compounds
- Pyridines
- regorafenib
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Topics |
- Adult
- Aged
- Angiogenesis Inhibitors
(therapeutic use)
- Colorectal Neoplasms
(blood supply, drug therapy, pathology)
- Drug Resistance, Neoplasm
- Female
- Humans
- Male
- Middle Aged
- Neovascularization, Pathologic
(drug therapy)
- Phenylurea Compounds
(therapeutic use)
- Pyridines
(therapeutic use)
- Salvage Therapy
- Survival Rate
- Treatment Outcome
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