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About Stivarga® (regorafenib) in mCRC
Now NICE and SMC recommended as an alternative to continued cytotoxic chemotherapy in mCRC
Stivarga is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumour angiogenesis (VEGFR1, 2, 3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumour immunity (CSF-1R).
Stivarga is indicated as monotherapy for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy.
Stivarga is an established oral TKI with proven efficacy from clinical trials with >8,000 patients, as well as >500,000 patients treated worldwide over the last 10 years.
- Mechanism of actionexpand_more
Stivarga provides a proven option that may help patients when tumours stop responding to chemotherapy
mCRC cells may become resistant to chemotherapy-based regimens. Stivarga is an oral, multitargeted TKI that actively inhibits tumour growth, survival and spread through four key mechanisms.
Introducing a different MoA may help patients who have developed resistance to chemotherapy-based regimens without precluding future chemotherapy-based treatments. Switching to Stivarga is associated with better outcomes vs a complete break from treatment.
Learn more about Stivarga and it’s antitumour activities - Efficacyexpand_more
Demonstrated extended OS in both Phase 3, randomised, controlled trials and real-world studies.
Patients treated with Stivarga had improved OS vs placebo in mCRC patients, regardless of KRAS and BRAF mutation status.
Trials presented for completeness, not intended for head-to-head comparison.
Phase 3 clinical trial overview:
CORRECT: an international, multicentre, randomised, placebo-controlled trial (N=760; Stivarga + BSC, n=505; placebo + BSC, n=255).
CONCUR: a randomised, double-blind, placebo-controlled trial in Asian patients (N=204; Stivarga + BSC, n=136; placebo + BSC, n=68).
Adult patients in the treatment arm were treated with Stivarga 160 mg orally, once daily + BSC 3 weeks on, 1 week off.
Median OS (primary endpoint) in CORRECT
The 12-month OS rate with Stivarga in CORRECT was 24%
6.4 months vs 5.0 months
HR: 0.77 (95% CI: 0.64–0.94); p=0.0052; one-sided)
BSC: best supportive care; HR: hazard ratio; CI: confidence interval; OS: overall survival
Median OS (primary endpoint) in CONCUR
Stivarga extended OS regardless of KRAS status or age group
8.8 months vs 6.3 months
HR: 0.55 (95% CI: 0.40–0.77); p=0.00016; one-sided
- Safetyexpand_more
Stivarga has a manageable, well-established safety profile across Phase 3 and real-world studies
- The most common adverse events typically occurred in treatment cycles 1–2, and most declined over time with subsequent treatment cycles
- Grade 3/4 neutropaenia, anaemia and thrombocytopaenia occurred in <5% of the study population in both CORRECT and CONCUR
- In the CONCUR study, only 1.5% of patients required a dose delay due to neutropaenia
- The Phase 3 trials had low incidences of severe haematological toxicity
- The most frequently observed adverse drug reactions (≥30%) in patients receiving Stivarga are pain, hand foot skin reaction (HFSR), asthenia/fatigue, diarrhoea, decreased appetite and food intake, hypertension and infection. Please consult the SmPC before prescribing.
- Dose modificationsexpand_more
Dose modifications for Stivarga can be made for HFSR and LFT abnormalities, if needed
Stivarga dosing in the pivotal trial comprised a 4-week cycle repeated each month:
- 4 tablets, each containing 40 mg, taken orally once daily for 3 weeks followed by a 1 week treatment break comprises a cycle of 4 weeks
- No dose adjustments are required based on age; mild, moderate or severe renal impairment; mild or moderate hepatic impairment; gender or ethnicity
- Stivarga should be taken with water at the same time each day, after a light meal that contains less than 30% fat
- Treatment should continue as long as benefit is observed or until unacceptable toxicity occurs
Adjustable dosing for management of HFSR and LFT abnormalities:
- Modify dose to maintain tolerability if required
- Recommended starting dose of 160 mg can be reduced in 40 mg decrements to manage AEs
- Dose can be re-escalated upon resolution of HFSR and LFT, check SmPC for more information
Please refer to Stivarga SmPC for full dosing information prior to prescribing.
HFSR: hand foot skin reaction; LFT: Liver function test
- 4 tablets, each containing 40 mg, taken orally once daily for 3 weeks followed by a 1 week treatment break comprises a cycle of 4 weeks
- Treatment planningexpand_more
Stivarga offers an alternative option after chemotherapy-based agents and does not preclude subsequent chemotherapy usage.
Use Stivarga as part of the mCRC treatment sequence
Expert guidelines validate the use of Stivarga in mCRC after recommended upfront chemo-based regimens
Adapted from NICE TA8661 and Cervantes, et al. 2023.
© NICE 2023 Regorafenib for previously treated metastatic colorectal cancer. Available from https://www.nice.org.uk/guidance/ta866 (Accessed February 2024). All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.* In RAS-wt patients not previously treated with anti-EGFR monoclonal antibodies.
† Treatment for BRAF-mut patients if not used in the second line.mCRC: metastatic colorectal cancer; mut: mutation; wt: wild-type.
Proportion of patients able to receive cytotoxic therapy following treatment with Stivarga
PP-STI-GB-0450 | March 2025
- Referencesexpand_more
- 1NICE. Technology appraisal guidance TA866. Published: February 2023. Regorafenib for previously treated metastatic colorectal cancer. Available at: www.nice.org.uk/guidance/ta866 (Last Accessed February 2024)
- 2SMC. Medicines advice 2562 - regorafenib. Available from: https://www.scottishmedicines.org.uk/medicines-advice/regorafenib-stivarga-full-smc2562 (Accessed February 2024).
- 3STIVARGA (regorafenib) Summary of Product Characteristics.
- 4Data on file. Bayer HealthCare Pharmaceuticals, Inc. [BAY 73-4506]. November 2020.
- 5Santini D, et al. Ann Oncol. 2012;23:2313–8.
- 6Arai H, et al. Cancer Treat Rev. 2019;81:101912.
- 7Grothey A. Clin Adv Hematol Oncol. 2020;17:2–4
- 8Tonini G, et al. J Exp Clin Cancer Res. 2013;32:1–8.
- 9Grothey A, et al. Lancet. 2013;381:303–12.
- 10Li J, et al. Lancet Oncol. 2015;16:619–29.
- 11Ducreux M, et al. Eur J Cancer. 2019;123:146–54.
- 12Van Cutsem E, et al. Ann Oncol. 2016;27:1386–422.
- 13Grothey A, et al. Oncologist. Abstract presented at: ASCO 2013; Chicago, IL. Abstract 3637.
- 14Cervantes A, et al. Ann Oncol. 2023;34:10–32.
- 15Mayer RJ, et al. NEJM. 2015;372:1909–19.
- 16Bachet JB, et al. ESMO Open. 2020;5:e000698.
- 17Kidd M, et al. Poster presented at: American Society of Clinical Oncology (ASCO) 2015, Gastrointestinal Cancers Symposium; May 29–June 2, 2015; Chicago IL. Poster 678.