Hui Shan Tan1, Huihua Li2, Yu Wen Hong3, Chee-Keong Toh1, Alvin Wong4, Gilberto Lopes5, Miah Hiang Tay6, Alexandre Chan3, Xin Yao7, Tiffany Tang1, Quan Sing Ng1, Ravindran Kanesvaran1, Noan Minh Chau1, Min-Han Tan8. 1. Department of Medical Oncology, National Cancer Centre Singapore, Singapore. 2. Department of Health Services Research, Singapore General Hospital, Singapore. 3. Oncology Pharmacy, National Cancer Centre Singapore, Singapore; Department of Pharmacy, National University of Singapore, Singapore. 4. Department of Haematology-Oncology, National University Health System, Singapore. 5. Johns Hopkins International Medical Centre, Singapore. 6. Onco-Care Cancer Centre, Gleneagles Hospital, Singapore. 7. Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China. 8. Department of Medical Oncology, National Cancer Centre Singapore, Singapore; Institute of Bioengineering and Nanotechnology, Singapore. Electronic address: tan.min.han@nccs.com.sg.
Abstract
BACKGROUND: The use of sunitinib at conventional doses (50 mg/d, 6-week cycles: 4 weeks of treatment, then 2 weeks of no treatment) in Asian patients with metastatic renal cell carcinoma (mRCC) is associated with high real-world toxicities. PATIENTS AND METHODS: Patients with mRCC treated with sunitinib between 2005 and 2012 at 4 centers representing a near-national cohort (n = 160) in Singapore were evaluated. One hundred twenty-seven consecutive patients in 1 center were treated with a novel attenuated-dose sunitinib regimen (37.5 mg/d, 6-week cycle: 4 weeks of treatment, then 2 weeks of no treatment) with outcomes captured in a prospective registry. Efficacy and safety outcomes of these patients were compared against those who received sunitinib at conventional dosing (n = 33) at all 4 centers. Statistical modeling was adjusted for baseline prognostic criteria and therapy line where possible. RESULTS: Overall survival from treatment initiation (OSinitiation), overall survival from the first documented metastasis (OStotal), and progression-free survival (PFS) were similar for patients who received first-line sunitinib for conventional relative to attenuated dose regimens (OSinitiation: 18.3 vs. 16.5 months, respectively; P = .54; OStotal: 27.4 vs. 21.8 months, respectively; P = .45; PFS: 6.7 vs. 7.9 months, respectively; P = .64), similar to real-world outcomes in Western studies. A marked lower rate of severe toxicities, dose delays, and reductions were observed with the attenuated dose regimen, with 75/127 (59%), rather than 28/33 (85%) for the conventional dose arm who experienced Grade ≥ 3 toxicities (P = .0088); 31/127 (24%) rather than 19/33 (58%) who experienced dose delays (P = .0004); and 44/127 (35%) rather than 23/33 (70%) who experienced dose reduction (P = .0005) during their course of treatment. CONCLUSION: An attenuated dose regimen of sunitinib yielded comparable real-world efficacy outcomes, with considerable reduction in toxicities as documented in a prospective registry.
BACKGROUND: The use of sunitinib at conventional doses (50 mg/d, 6-week cycles: 4 weeks of treatment, then 2 weeks of no treatment) in Asian patients with metastatic renal cell carcinoma (mRCC) is associated with high real-world toxicities. PATIENTS AND METHODS: Patients with mRCC treated with sunitinib between 2005 and 2012 at 4 centers representing a near-national cohort (n = 160) in Singapore were evaluated. One hundred twenty-seven consecutive patients in 1 center were treated with a novel attenuated-dose sunitinib regimen (37.5 mg/d, 6-week cycle: 4 weeks of treatment, then 2 weeks of no treatment) with outcomes captured in a prospective registry. Efficacy and safety outcomes of these patients were compared against those who received sunitinib at conventional dosing (n = 33) at all 4 centers. Statistical modeling was adjusted for baseline prognostic criteria and therapy line where possible. RESULTS: Overall survival from treatment initiation (OSinitiation), overall survival from the first documented metastasis (OStotal), and progression-free survival (PFS) were similar for patients who received first-line sunitinib for conventional relative to attenuated dose regimens (OSinitiation: 18.3 vs. 16.5 months, respectively; P = .54; OStotal: 27.4 vs. 21.8 months, respectively; P = .45; PFS: 6.7 vs. 7.9 months, respectively; P = .64), similar to real-world outcomes in Western studies. A marked lower rate of severe toxicities, dose delays, and reductions were observed with the attenuated dose regimen, with 75/127 (59%), rather than 28/33 (85%) for the conventional dose arm who experienced Grade ≥ 3 toxicities (P = .0088); 31/127 (24%) rather than 19/33 (58%) who experienced dose delays (P = .0004); and 44/127 (35%) rather than 23/33 (70%) who experienced dose reduction (P = .0005) during their course of treatment. CONCLUSION: An attenuated dose regimen of sunitinib yielded comparable real-world efficacy outcomes, with considerable reduction in toxicities as documented in a prospective registry.