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Incidence of side effects during multikinase inhibitor treatment

The mechanism of action of multikinase inhibitors can result in unique side effects that may be associated with the specific molecular target or mechanism which the compound is targeting, or may be non-specific.1 Cutaneous effects with multikinase inhibitor treatment are very common (≥1/10) or common (≥1/100 to <1/10) 2-13 with incidence for individual skin toxicities varying depending on the drug and tumour indication. Skin-related side effects may lead to changes in dosing due to severity, and both physical and psychological discomfort or pain.1

While predominantly mild, patients may experience clinically unusual or severe cutaneous side effects, most notably, hand-foot skin reaction.1 Severe (grade 3) hand-foot skin reaction has been described in 17% of patients with metastatic colorectal cancer treated with regorafenib in the phase III trials.14 Also, in 8% of patients with renal cell carcinoma and 17% of patients with hepatocellular carcinoma treated with cabozantinib, a similar proportion in patients with progressive metastatic medullary thyroid cancer treated with cabozantinib, 6% of patients with renal cell carcinoma and 8% of patients with the unresectable hepatocellular carcinoma treated and 19% of patients with differentiated thyroid carcinoma treated with sorafenib.15-24

As skin reactions tend to vary between patients and show different kinetics based on the particular compound and cutaneous effect, data on incidence and course can be inconsistent. However, the following figure demonstrates the onset of hand-foot skin reaction seen with the multikinase inhibitor regorafenib, as an example.25

Figure: Frequency of hand-foot skin reaction over time in regorafenib-treated patients. 

Frequency of hand-foot skin reaction over timein regorafenib-treated patients

Adapted from: Grothey A, et al.
Time profile of adverse events (AEs) from regorafenib (REG) treatment for metastatic colorectal cancer (mCRC) in the phase III CORRECT study. ASCO 2013; abstract 3637. One treatment cycle for regorafenib is a 4-week period consisting of 3 weeks “on therapy” (when the patient takes daily the recommended dose of regorafenib) followed by 1 week “off therapy”. Treatment cycles are repeated as long as benefit is observed or until unacceptable toxicity occurs.


  1. Guztmer R, et al. Dtsch Arztebl Int. 2012;109:133–140.
  2. European Medicines Agency. Stivarga (regorafenib) Summary of Product Characteristics 2018.
  3. European Medicines Agency. Nexavar (sorafenib) Summary of Product Characteristics 2018.
  4. European Medicines Agency. Caprelsa (vandetanib) Summary of Product Characteristics 2019.
  5. European Medicines Agency. Sutent (sunitinib) Summary of Product Characteristics 2019.
  6. European Medicines Agency. Glivec (imatinib) Summary of Product Characteristics 2019.
  7. European Medicines Agency. Cabometyx (cabozantinib) Summary of Product Characteristics 2019.
  8. European Medicines Agency. Cometriq (cabozantinib) Summary of Product Characteristics 2019.
  9. European Medicines Agency. Kisplyx (lenvatinib) Summary of Product Characteristics 2019.
  10. European Medicines Agency. Lenvima (lenvatinib) Summary of Product Characteristics 2019.
  11. European Medicines Agency. Sprycel (dasatinib) Summary of Product Characteristics 2019.
  12. European Medicines Agency. Votrient (pazopanib) Summary of Product Characteristics 2018.
  13. European Medicines Agency. Rydapt (midostaurin) Summary of Product Characteristics 2018.
  14. Food and Drug Administration. Stivarga (regorafenib) Prescribing Information 2019.
  15. Food and Drug Administration. Nexavar (sorafenib) Prescribing Information 2018.
  16. Food and Drug Administration. Caprelsa (vandetanib) Prescribing Information 2018.
  17. Food and Drug Administration. Sutent (sunitinib) Prescribing Information 2019.
  18. Food and Drug Administration. Gleevec (imatinib) Prescribing Information 2018.
  19. Food and Drug Administration. Cabometyx (cabozantinib) Prescribing Information 2019.
  20. Food and Drug Administration. Cometriq (cabozantinib) Prescribing Information 2018.
  21. Food and Drug Administration. Lenvima (lenvatinib) Prescribing Information 2018.
  22. Food and Drug Administration. Sprycel (dasatinib) Prescribing Information 2018.
  23. Food and Drug Administration. Votrient (pazopanib) Prescribing Information 2017.
  24. Food and Drug Administration. Rydapt (midostaurin) Prescribing Information 2018.
  25. Grothey A, et al. ASCO 2013; abstract 3637.

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