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Original Investigation |

Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression

Martina Sanlorenzo, MD1,2; Igor Vujic, MD1,3; Adil Daud, MD1; Alain Algazi, MD1; Matthew Gubens, MD1; Sara Alcántara Luna, MD1; Kevin Lin, BS1; Pietro Quaglino, MD2; Klemens Rappersberger, MD3; Susana Ortiz-Urda, MD, PhD, MBA1
[+] Author Affiliations
1Mt Zion Cancer Research Center, Department of Dermatology, University of California–San Francisco
2Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy
3Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria
JAMA Dermatol. 2015;151(11):1206-1212. doi:10.1001/jamadermatol.2015.1916.
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Importance  Immunomodulatory anticancer drugs, such as the anti–programmed death-1 drug pembrolizumab, have shown promising results in trials, and more patients will receive such treatments. Little is known about cutaneous adverse events (AEs) caused by these drugs and their possible correlation with treatment response.

Objective  To describe the frequency and spectrum of cutaneous AEs linked with pembrolizumab and their possible correlation with treatment response.

Design, Setting, and Participants  A single-institution, retrospective medical record review was conducted of patients with cancer who were treated with pembrolizumab from March 1, 2011, to May 28, 2014. The review comprised 83 consecutive patients who were enrolled in 2 clinical trials, received at least 1 dose of pembrolizumab, and had at least 1 follow-up visit. Patients were grouped according to the following therapeutic regimen for pembrolizumab: 43 received 10 mg/kg every 3 weeks, 24 received 10 mg/kg every 2 weeks, and 16 received 2 mg/kg every 3 weeks. Sixty-six patients were treated for melanoma, 15 patients for lung cancer, 1 patient for prostate cancer, and 1 patient for Merkel cell carcinoma. Median follow-up was 15 weeks (range, 2-105 weeks). The analysis was conducted from March 1 to September 30, 2014.

Main Outcomes and Measures  Occurrence, severity, and type of cutaneous AEs, as well as disease progression and response to pembrolizumab treatment.

Results  Thirty-five patients (42%) developed cutaneous AEs attributed to pembrolizumab. The most common cutaneous AEs were macular papular eruption (24 [29%]), pruritus (10 [12%]), and hypopigmentation (7 [8%]). All 7 patients who developed hypopigmentation were treated for melanoma. Survival analyses showed that patients who developed cutaneous AEs had significantly longer progression-free intervals in all 3 groups (pembrolizumab, 10 mg/kg, every 3 weeks, P = .001; pembrolizumab, 10 mg/kg, every 2 weeks, P = .003; pembrolizumab, 2 mg/kg, every 3 weeks, P = .009) compared with patients who did not develop cutaneous AEs.

Conclusions and Relevance  Pembrolizumab therapy was associated with cutaneous AEs in 42% of patients. The development of cutaneous AEs, especially of hypopigmentation in patients with melanoma, could point toward better treatment response.

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Figure 1.
Cutaneous Adverse Events During Treatment With Pembrolizumab

A, Macular papular eruption involving the dorsal surfaces of both hands. B, Macular papular eruption involving the palmar surface of both hands. C, Spontaneous hypopigmentation (vitiligo) on and around lips. D, Scaly macular papular eruption on the lower back with some hypopigmented postinflammatory regions.

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Figure 2.
Grade 3 Cutaneous Adverse Events in a Patient Treated With Pembrolizumab

A, Macular papular eruption with predilection sites on photoexposed areas of the chest. B, Macular papular eruption with predilection sites on photoexposed areas of the arm.

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Figure 3.
Kaplan-Meier Survival Curves for Progression-Free Survival and Multivariate Cox Proportional Hazard Regression Models Corrected for the Number of Pembrolizumab Cycles

A, Patients treated with 10 mg/kg every 3 weeks. B, Patients treated with 10 mg/kg every 2 weeks. C, Patients treated with 2 mg/kg every 2 weeks. Patients who developed cutaneous adverse events have a longer progression-free interval in all treatment groups. HR indicates hazard ratio.

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