Clinical Management of EGFRI Dermatologic Toxicities: The Japanese Perspective

Clinical Management of EGFRI Dermatologic Toxicities: The Japanese Perspective

ABSTRACT: Epidermal growth factor receptor inhibitors (EGFRIs) have demonstrated clinical activity in patients with non–small-cell lung cancer, pancreatic cancer, and colorectal cancer. EGFRIs are generally well tolerated, but reversible dermatologic toxicities are commonly associated with their use. Limited clinical evidence has characterized these adverse reactions as a class effect. For panitumumab (Vectibix), mild-to-moderate dermatologic toxicities are the most common associated adverse reactions. This report details the Japanese experience in the management of dermatologic toxicities associated with panitumumab use. Treatment selection for skin toxicity in Japan is also detailed, with a flowchart depicting strategies to treat various stages of dermatologic toxicities. Panitumumab was well tolerated in Japanese patients with advanced solid tumors, with a safety profile similar to that seen in non-Japanese patients.


In a study reported by Yamada et al,[1] investigators evaluated the safety and pharmacokinetics of panitumumab (Vectibix) monotherapy in Japanese patients with advanced solid tumors. Primary objectives were to assess safety and evaluate pharmacokinetics. The secondary objectives were to assess immunogenicity (antipanitumumab antibody response) and clinical efficacy (objective tumor response) in Japanese patients with advanced solid tumors.

Patients were enrolled sequentially into one of three cohorts—2.5 mg/kg weekly, 6.0 mg/kg every 2 weeks, and 9.0 mg/kg every 3 weeks—and continued treatment until disease progression or drug intolerability. Patients were enrolled into the next dose cohort following evaluation of dose-limiting toxicity and safety data 4 weeks after the first infusion on the previous cohort.


Dermatologic Toxicities Observed in This Study

A total of 18 patients (6 per cohort) were enrolled and received at least one dose of panitumumab. At the time of the report, the median follow-up time was 16.5 weeks in cohort 1, 13.5 weeks in cohort 2, and 12 weeks in cohort 3. No dose-limiting toxicities were reported in this study. Some degree of skin-related toxicity was seen in all patients. Dermatologic toxicity was defined as any toxicity in the integument or eye.

The dermatologic toxicities observed in this study were predictable and generally tolerable. The reaction often took the form of clusters of monomorphous pustular lesions that resembled an acneiform-type drug eruption. The manifestations were similar in most affected patients and typically involved the upper trunk and face. The dermatologic manifestations were usually associated with only minimal symptoms but were cosmetically distressing for some patients. The reactions typically occurred 1 week after administration of panitumumab and rarely affected patients as early as day 3. Treatment for these adverse effects continued for as many as 91 days, while patients were still on therapy.


Time to First Skin Toxicity

The first dermatologic toxicity was seen in a median of 7 days (Kaplan-Meier estimate; 95% confidence interval = 5–8 days). In cohort 1, the median was 7 days (range, 3–11); in cohort 2, it was 8 days (range, 5–9); and in cohort 3, it was also 8 days (range, 3–8). The median time to the most severe skin toxicity was day 11 (range, 8–14) in all patients (n = 18). In cohort 1, the median time to the most severe skin toxicity was 14 days (range, 7–20); in cohort 2, it was 11 days (range, 9–14); and in cohort 3, it was 9 days (range, 8–14) [Amgen data on file].


Treatment Selection for Skin Toxicity in Japan

EGFR inhibitors are generally well tolerated and do not have any of the severe systemic side effects seen with cytotoxic agents. However, these agents do cause skin toxicity, most often a papulopustular reaction (PPR).[2-5]


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