Pembrolizumab Cutaneous Adverse Events May Predict Better Response


Key Points

  • Time to progression was longer in patients who developed cutaneous adverse events.
  • Patients who developed cutaneous adverse events received more pembrolizumab treatment cycles.

In a single-center retrospective review reported in JAMA Dermatology, Sanlorenzo et al found that cutaneous adverse events in patients receiving the anti–PD-1 agent pembrolizumab (Keytruda), currently approved for treatment of melanoma, may indicate better treatment response.

Study Details

The study was a retrospective record review of 83 consecutive patients treated with pembrolizumab in two studies from March 2011 to May 2014 at the University of California, San Francisco, who had received at least one dose of pembrolizumab and had at least one follow-up visit. Among the patients, 66 had melanoma, 15 lung cancer, 1 prostate cancer, and 1 Merkel cell carcinoma. Patients received pembrolizumab regimens of 10 mg/kg every 3 weeks (n = 43), 10 mg/kg every 2 weeks (n = 24), and 2 mg/kg every 3 weeks (n = 16).

Median follow-up was 15 weeks (range = 2–105 weeks). Overall, 35 patients (42%) developed cutaneous adverse events attributed to pembrolizumab, with the most common being macular papular eruption (29%), pruritus, (12%), and hypopigmentation (8%), with all cases of hypopigmentation occurring in melanoma patients.

According to regimen, patients with vs without cutaneous adverse events had longer progression-free intervals among those receiving 10 mg/kg every 3 weeks (n = 19 vs 24; P = .001), 10 mg/kg every 2 weeks (n = 7 vs 17; P = .003), or 2 mg/kg every 3 weeks (n = 9 vs 7; P = .009). Patients who developed cutaneous adverse events had a greater median number of pembrolizumab cycles: 17 vs 4.5 (P < .001) in the 10 mg/kg every-3-week group, 10 vs 6 (P = .02) in the 10 mg every-2-week group, and 18 vs 4 (P = .05).

On multivariate analysis including number of pembrolizumab cycles, the benefit in time to progression remained significant in the lowest-dose group (hazard ratio = 0.12, P = .02). Hazard ratios in the 10 mg/kg every-3-week group (0.82, P =.81) and the 10 mg/kg every-2-week group (0.70, P = .79) favored the patients with cutaneous adverse events but were not significant.

The investigators concluded: “Pembrolizumab therapy was associated with cutaneous [adverse events] in 42% of patients. The development of cutaneous [adverse events], especially of hypopigmentation in patients with melanoma, could point toward better treatment response.”

Martina Sanlorenzo, MD, of the University of California, San Francisco, is the corresponding author for the JAMA Dermatology article.

The study was supported by the National Cancer Institute and Melanoma Research Alliance.

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