Incidence

The mechanism of action of multikinase inhibitors can result in unique side effects that may be associated with the specific targeted structure or mechanism for which the compound is targeting, or which may be non-specific.1 Cutaneous effects with Multikinase inhibitor treatment are common2-6, and reported to occur in up to 34% of patients, although some cutaneous side effects may have a higher incidence.1-6 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.1 For instance, severe (grade 3–4) rash is reported to occur in up to 13% of patients, severe Hand-foot skin reaction in up to 17%, severe Stomatitis in up to 6%, and severe photosensitivity in up to 2% of patients treated with multikinase inhibitors.2-6,7-11

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 unreliable. However, the following figure demonstrates the onset of hand-foot skin reaction seen with the multikinase inhibitor regorafenib over a 4-week treatment cycle, as an example.12

Frequency of Hand-foot skin reaction over time in 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.

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

References

1Guztmer R, et al. Cutaneous side effects of new antitumor drugs: clinical features and management. Dtsch Arztebl Int. 2012;109:133–140.
2European Medicines Agency. Stivarga® (regorafenib) Summary of Product Characteristics 2013.
3European Medicines Agency. Nexavar® (sorafenib) Summary of Product Characteristics 2014.
4European Medicines Agency. Caprelsa® (vandetanib) Summary of Product Characteristics 2014.
5European Medicines Agency. Sutent® (sunitinib) Summary of Product Characteristics 2014.
6European Medicines Agency. Glivec® (imatinib) Summary of Product Characteristics 2014.
7Food and Drug Administration. Stivarga® (regorafenib) Prescribing Information 2013.
8Food and Drug Administration. Nexavar® (sorafenib) Prescribing Information 2013.
9Food and Drug Administration. Caprelsa® (vandetanib) Prescribing Information 2014.
10Food and Drug Administration. Sutent® (sunitinib) Prescribing Information 2013.
11Food and Drug Administration. Gleevec® (imatinib) Prescribing Information 2013.
12Grothey A, Sobrero A.F., Siena S., et al Time profile of adverse events (AEs) from regorafenib (REG) treatment for metastatic colorectal cancer (mCRC) in the phase III CORRECT study. J Clin Oncol 31, 2013 (suppl; abstr 3637)

Last update: 22 August 2014