PMID- 26222619 OWN - NLM STAT- MEDLINE DCOM- 20160225 LR - 20220409 IS - 2168-6084 (Electronic) IS - 2168-6068 (Print) IS - 2168-6068 (Linking) VI - 151 IP - 11 DP - 2015 Nov TI - Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression. PG - 1206-1212 LID - 10.1001/jamadermatol.2015.1916 [doi] AB - 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. FAU - Sanlorenzo, Martina AU - Sanlorenzo M AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Vujic, Igor AU - Vujic I AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Daud, Adil AU - Daud A AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Algazi, Alain AU - Algazi A AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Gubens, Matthew AU - Gubens M AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Luna, Sara Alcantara AU - Luna SA AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Lin, Kevin AU - Lin K AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Quaglino, Pietro AU - Quaglino P AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Rappersberger, Klemens AU - Rappersberger K AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). FAU - Ortiz-Urda, Susana AU - Ortiz-Urda S AD - Mt Zion Cancer Research Center, Department of Dermatology, University of California-San Francisco (Sanlorenzo, Vujic, Daud, Algazi, Gubens, Luna, Lin, Ortiz-Urda); Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy (Sanlorenzo, Quaglino); Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria (Vujic, Rappersberger). LA - eng GR - K08 CA155035/CA/NCI NIH HHS/United States GR - K08CA155035/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Dermatol JT - JAMA dermatology JID - 101589530 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use MH - Antineoplastic Agents/*adverse effects/therapeutic use MH - Disease Progression MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Neoplasms/*drug therapy/pathology MH - Retrospective Studies MH - Severity of Illness Index MH - Skin Diseases/*chemically induced/epidemiology/pathology MH - Treatment Outcome MH - Young Adult PMC - PMC5061067 MID - NIHMS817441 EDAT- 2015/07/30 06:00 MHDA- 2016/02/26 06:00 PMCR- 2016/10/12 CRDT- 2015/07/30 06:00 PHST- 2015/07/30 06:00 [entrez] PHST- 2015/07/30 06:00 [pubmed] PHST- 2016/02/26 06:00 [medline] PHST- 2016/10/12 00:00 [pmc-release] AID - 10.1001/jamadermatol.2015.1916 [doi] PST - ppublish SO - JAMA Dermatol. 2015 Nov;151(11):1206-1212. doi: 10.1001/jamadermatol.2015.1916.