Management of Dermatologic Complications of Lung Cancer Therapies

  • Silvina B. Pugliese
  • Joel W. Neal
  • Bernice Y. Kwong
Lung Cancer (HA Wakelee, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Lung Cancer

Opinion statement

In recent years, oncogene-directed targeted agents and immunotherapies have expanded the treatment armamentarium for advanced lung cancer and, in particular, non-small cell lung cancer (NSCLC). Along with extended survival, these agents are accompanied by a host of cutaneous complications that affect the skin, hair, and nails. These skin complications range from the well-characterized papulopustular (acneiform) eruption of the epidermal growth factor receptor (EGFR) inhibitors to the emerging characterization of lichenoid skin eruptions seen during treatment with antibodies targeting the programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand (PD-L1). When promptly recognized and accurately diagnosed, most cutaneous adverse events can be managed with supportive treatments, avoiding the need to interrupt antitumor therapy. Furthermore, preemptive management of skin problems can lead to significantly decreased severity of many cutaneous complications of these therapies. We encourage close collaboration between dermatologists and oncologists to better characterize cutaneous toxicity, select appropriate management, and avoid unnecessary dose reduction or discontinuation while simultaneously improving patient quality of life.

Keywords

Oncodermatology Skin toxicity Lung cancer Epidermal growth factor receptor inhibitor Vascular endothelial growth factor inhibitor Anaplastic kinase lymphoma inhibitor Programmed cell death protein 1 PD-1 BRAF inhibitor Immunotherapy Checkpoint inhibitor Papulopustular eruption Xerosis Pruritus Paronychia Pyogenic granuloma Photosensitivity Pruritus Hair Nails Rash 

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.••
    Kris MG, Johnson B, Berry L, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998–2006. This study showed that the majority of lung adenocarcinomas have an identifiable oncogenic driver and that matching targeted therapies to these drivers allowed individuals to live longer.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Kyllo RL, Anadkat MJ. Dermatologic adverse events to chemotherapeutic agents, part 1: cytotoxics, epidermal growth factor receptors, multikinase inhibitors, and proteasome inhibitors. Semin Cutan Med Surg. 2014;33(1):28–39.CrossRefPubMedGoogle Scholar
  3. 3.•
    Rosen AC, Case EC, Dusza SW, et al. Impact of dermatologic adverse events on quality of life in 283 cancer patients: a questionnaire study in a dermatology referral clinic. Am J Clin Dermatol. 2013;14(4):327–33. Patient quality-of-life was noted to be negatively affected by the skin toxicities associated with chemotherapy. Quality-of-life scores were lower for patients on targeted therapy as compared to conventional therapy.CrossRefPubMedGoogle Scholar
  4. 4.
    Reyes-Habito CM, Roh EK. Cutaneous reactions to chemotherapeutic drugs and targeted therapy for cancer: part II. Targeted therapy. J Am Acad Dermatol. 2014;71(2):217.e1–217.Google Scholar
  5. 5.
    Makrilia N, Syrigou E, Kaklamanos I, et al. Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review. Met Based Drugs. 2010;2010.Google Scholar
  6. 6.
    Litt JZ. Litt’s Drug Eruption and Reaction Database. http://www.drugeruptiondata.com.laneproxy.stanford.edu/. Accessed 5 April 2015.
  7. 7.
    Piraccini BM, Alessandrini A. Drug-related nail disease. Clin Dermatol. 2013;31(5):618–26.Google Scholar
  8. 8.
    Aydogan I, Kavak A, Parlak AH, et al. Persistent serpentine supravenous hyperpigmented eruption associated with docetaxel. J Eur Acad Dermatol Venereol. 2005;19(3):345–7.Google Scholar
  9. 9.
    ABRAXANE. Celgene. Revised December 2014. http://www.abraxane.com/downloads/Abraxane_PrescribingInformation.pdf. Accessed 6 April 2015.
  10. 10.
    Mitsudomi T. Molecular epidemiology of lung cancer and geographic variations with special reference to EGFR mutations. Transl Lung Cancer Res. 2014;3(4):205–11.Google Scholar
  11. 11.
    U.S. Food and Drug Administration. Erlotinib. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm352317.htm. Updated May 15 2013. Accessed 1 April 2015.
  12. 12.
    U.S. Food and Drug Administration. Afatinib. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm360574.htm. Updated July 12 2013. Accessed 1 April 2015
  13. 13.
    Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009;373(9674):1525–31.Google Scholar
  14. 14.
    Janjigian YY, Smit EF, Groen HJ, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014;4(9):1036–45.Google Scholar
  15. 15.
    Thatcher N, Hirsch FR, Szczesna A, et al. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). 2014 ASCO Annual Meeting. J Clin Oncol. 2014;32:5s (suppl; abstr 8008^).Google Scholar
  16. 16.
    Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6(10):803–12.Google Scholar
  17. 17.
    Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009;361(10):958–67.Google Scholar
  18. 18.
    Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012;13(5):528–38.Google Scholar
  19. 19.
    Yang JC, Shih JY, Su WC, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012;13(5):539–48.Google Scholar
  20. 20.
    Yang JC, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141–51.Google Scholar
  21. 21.
    Sequist LV, Soria JC, Goldman JW, et al. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2015;372(18):1700–9.Google Scholar
  22. 22.
    Janne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015;372(18):1689–99.Google Scholar
  23. 23.
    Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (2009). http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7. Accessed 30 May 2015.
  24. 24.
    Lacouture ME, Anadkat MJ, Bensadoun RJ, et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19(8):1079–95.Google Scholar
  25. 25.
    Shah NT, Kris MG, Pao W, et al. Practical management of patients with non-small-cell lung cancer treated with gefitinib. J Clin Oncol. 2005;23(1):165–74.Google Scholar
  26. 26.
    Nakahara T, Moroi Y, Takayama K, et al. Changes in sebum levels and the development of acneiform rash in patients with non-small cell lung cancer after treatment with EGFR inhibitors. Onco Targets Ther. 2015;8:259–63.Google Scholar
  27. 27.••
    Bachet JB, Peuvrel L, Bachmeyer C, et al. Folliculitis induced by EGFR inhibitors, preventive and curative efficacy of tetracyclines in the management and incidence rates according to the type of EGFR inhibitor administered: a systematic literature review. Oncologist. 2012;17(4):555–68. A thorough literature review investigating the use of tetracyclines for prophylactic and curative treatment of EGFR inhibitor papulopustular eruption. This study concluded that prophylactic tetracycline therapy should be routinely prescribed to all patients.Google Scholar
  28. 28.
    Lacouture ME, Mitchel EP, Piperdi B, et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28(8):1351–7.Google Scholar
  29. 29.
    Jatoi A, Rowland K, Sloan JA, et al. Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: results of a placebo-controlled trial from the North Central Cancer Treatment Group (N03CB). Cancer. 2008;113(4):847–53.Google Scholar
  30. 30.
    Deplanque G, Chavaillon J, Vergnenegre A, et al. CYTAR: a randomized clinical trial evaluating the preventive effect of doxycycline on erlotinib-induced folliculitis in non-small cell lung cancer patients. 2010 ASCO Annual Meeting. J Clin Oncol. 2010;28:15s (suppl; abstr 9019).Google Scholar
  31. 31.
    Scope A, Agero AL, Dusza SW, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25(34):5390–6.Google Scholar
  32. 32.••
    Liu H, Wu Y, Lv TF, et al. Skin rash could predict the response to EGFR tyrosine kinase inhibitor and the prognosis for patients with non-small cell lung cancer: a systematic review and meta-analysis. PLoS One. 2013;8(1):e55128. A review of clinic trials concluding that patients who developed a rash during EGFR inhibitor treatment had longer progression-free survival and overall survival than the control group.Google Scholar
  33. 33.
    Melosky BL, Anderson H, Burkes RL. Pan-Canadian rash trial with EGFR inhibitors. 2014 ASCO Annual Meeting. J Clin Oncol. 2014;32:5s (suppl; abstr 8013).Google Scholar
  34. 34.
    Macdonald JB, Macdonald B, Golitz LE, et al. Cutaneous adverse effects of targeted therapies. J Am Acad Dermatol. 2015;72(2):203–18.Google Scholar
  35. 35.
    Lacouture ME, Schadendorf D, Chu CY, et al. Dermatologic adverse events associated with afatinib: an oral ErbB family blocker. Expert Rev Anticancer Ther. 2013;13(6):721–8.Google Scholar
  36. 36.
    Chiang HC, Anadkat MJ. Isotretinoin for high-grade or refractory epidermal growth factor receptor inhibitor-related acneiform papulopustular eruptions. J Am Acad Dermatol. 2013;69(4):657–8.Google Scholar
  37. 37.
    Tomková H, Pospíšková M, Zábojníková M, et al. Phytomenadione pre-treatment in EGFR inhibitor-induced folliculitis. J Eur Acad Dermatol Venereol. 2013;27(4):514–9.Google Scholar
  38. 38.•
    Pinta F, Ponzetti A, Spadi R, et al. Pilot clinical trial on the efficacy of prophylactic use of vitamin K1-based cream (Vigorskin) to prevent cetuximab-induced skin rash in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2014;13(1):62–7. This trial studied the use of topical vitamin K1 as preventive treatment to avoid cetuximab-induced papulopustular rash in colorectal cancer patients. Patients were noted to have a lower incidence of grades 2–3 rashes as compared to the literature.Google Scholar
  39. 39.
    Amitay-Laish I, David M, Stemmer SM. Staphylococcus coagulase-positive skin inflammation associated with epidermal growth factor receptor-targeted therapy: an early and a late phase of papulopustular eruptions. Oncologist. 2010;15(9):1002–8.Google Scholar
  40. 40.
    Eilers RE, Gandhi M, Patel JD, et al. Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy. J Natl Cancer Inst. 2010;102(1):47–53.Google Scholar
  41. 41.
    Belum VR, Cercek A, Sanz-Motilva V, et al. Dermatologic adverse events to targeted therapies in lower GI cancers: clinical presentation and management. Curr Treat Options Oncol. 2013;14(3):389–404.Google Scholar
  42. 42.
    Meyer V, Kerk N, Mellmann A, et al. MRSA eradication in dermatologic outpatients—theory and practice. J Dtsch Dermatol Ges. 2012;10(3):186–96.Google Scholar
  43. 43.
    Jatoi A, Thrower A, Sloan JA, et al. Does sunscreen prevent epidermal growth factor receptor (EGFR) inhibitor-induced rash? Results of a placebo-controlled trial from the North Central Cancer Treatment Group (N05C4). Oncologist. 2010;15(9):1016–22.Google Scholar
  44. 44.••
    Valentine J, Belum VR, Duran J, et al. Incidence and risk of xerosis with targeted anticancer therapies. J Am Acad Dermatol. 2015;72(4):656–67. Xerosis is an important side effect of targeted therapy that can significantly reduce quality of life and interrupt treatment.Google Scholar
  45. 45.
    Hu JC, Sadeghi P, Pinter-Brown LC, et al. Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis, and management. J Am Acad Dermatol. 2007;56(2):317–26.Google Scholar
  46. 46.
    Busam KJ, Capodieci P, Motzer R, et al. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol. 2001;144(6):1169–76.Google Scholar
  47. 47.•
    Ensslin CJ, Rosen AC, Wu S, et al. Pruritus in patients treated with targeted cancer therapies: systematic review and meta-analysis. J Am Acad Dermatol. 2013;69(5):708–20. Pruritus is a common and important side effect of anticancer therapy that can significantly reduce quality of life and interrupt treatment.Google Scholar
  48. 48.•
    Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13(10):1020–4. Prospective study of aprepitant in treating pruritus induced by biological cancer treatment in 45 patients with metastatic solid tumors. Aprepitant effectively decreased severe pruritus with no reported adverse events.Google Scholar
  49. 49.
    Hepper DM, Wu P, Anadkat MJ. Scarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinib. J Am Acad Dermatol. 2011;64(5):996–8.Google Scholar
  50. 50.
    Yang BH, Bang CY, Byun JW, et al. A case of cicatricial alopecia associated with erlotinib. Ann Dermatol. 2011;23 Suppl 3:S350–3.Google Scholar
  51. 51.
    Toda N, Fujimoto N, Kato T, et al. Erosive pustular dermatosis of the scalp-like eruption due to gefitinib: case report and review of the literature of alopecia associated with EGFR inhibitors. Dermatology. 2012;225(1):18–21.Google Scholar
  52. 52.
    Day A, Abramson AK, Patel M, et al. The spectrum of oculocutaneous disease. J Am Acad Dermatol. 2014;70(5):821.e1–19.Google Scholar
  53. 53.
    Hachisuka J, Doi K, Moroi Y, et al. Successful treatment of epidermal growth factor receptor inhibitor-induced periungual inflammation with adapalene. Case Rep Dermatol. 2011;3(2):130–6.Google Scholar
  54. 54.
    Fontanella C, Ongaro E, Bolzonello S, et al. Clinical advances in the development of novel VEGFR2 inhibitors. Ann Transl Med. 2014;2(12):123.Google Scholar
  55. 55.
    U.S. Food and Drug Administration. Bevacizumab. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279177.htm. Updated December 7 2014. Accessed 20 April 2015.
  56. 56.
    Dhillon S. Nintedanib: a review of its use as second-line treatment in adults with advanced non-small cell lung cancer of adenocarcinoma histology. Target Oncol. 2015;10(2):303–10.Google Scholar
  57. 57.
    Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–50.Google Scholar
  58. 58.
    Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665–73.Google Scholar
  59. 59.
    Reck M, Kaiser R, Mellemgaard A, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014;15(2):143–55.Google Scholar
  60. 60.
    Saif MW, Longo WL, Israel G. Correlation between rash and a positive drug response associated with bevacizumab in a patient with advanced colorectal cancer. Clin Colorectal Cancer. 2008;7(2):144–8.Google Scholar
  61. 61.
    Gotli V, Khaled S, Lapko I, et al. Skin rash secondary to bevacizumab in a patient with advanced colorectal cancer and relation to response. Anticancer Drugs. 2006;17(10):1227–9.Google Scholar
  62. 62.
    Gavrilova M, Martin JM, Martin-Gorgojo A, et al. Follicular acneiform eruption induced by bevacizumab. Dermatol Online J. 2012;18(9):15.Google Scholar
  63. 63.
    Molina-Ruiz AM, Domine M, Requena L. Acute and severe acne in a patient treated with bevacizumab. Int J Dermatol. 2013;52:486–90.Google Scholar
  64. 64.
    Torino F, Sarmiento R, Gasparini G. The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer. Crit Rev Oncol Hematol. 2013;87(3):283–305.Google Scholar
  65. 65.
    AVASTIN (Bevacizumab) [package insert]. Genentech, Inc. Revised May 2009. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125085s0169lbl.pdf. Accessed 20 April 2015.
  66. 66.
    Fourcade S, Gaudy-Marqueste C, Tasei AM, et al. Localized skin necrosis of steroid-induced striae distensae: an unusual complication of bevacizumab and irinotecan therapy. Arch Dermatol. 2011;147:1227–8.Google Scholar
  67. 67.
    Dosal J, Handler MZ, Ricotti CA, et al. Ulceration of abdominal striae distensae (stretch marks) in a cancer patient. Arch Dermatol. 2012;148:385–90.Google Scholar
  68. 68.•
    Farber SA, Samimi S, Rosenbach M. Ulcerations within striae distensae associated with bevacizumab therapy. J Am Acad Dermatol. 2015;72:e33–5. Case report describing the development of ulcerations within striae secondary to bevacizumab therapy, reviewing potential pathophysiology and recommending treatment.Google Scholar
  69. 69.
    Peters KB, Coyle TE, Vredenburgh JJ, et al. Ulceration of striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy. J Neurooncol. 2011;101:155–9.Google Scholar
  70. 70.
    Zhao F, Xu M, Lei H, et al. Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusion gene: a meta-analysis. PLoS One. 2015;10(2):e0117333.Google Scholar
  71. 71.
    Wong DW, Leung EL, So KK, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer. 2009;115(8):1723–33.Google Scholar
  72. 72.
    Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94.Google Scholar
  73. 73.
    Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370(13):1189–97.Google Scholar
  74. 74.
    Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012;13(10):1011–9.Google Scholar
  75. 75.
    ZYKADIA (Ceritinib). Novartis Pharmaceuticals. Revised April 2014. http://www.pharma.us.novartis.com/product/pi/pdf/zykadia.pdf. Accessed 20 April 2015.
  76. 76.
    Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014;15(10):1119–28.Google Scholar
  77. 77.
    Oser MG, Pasi AJ. A severe photosensitivity dermatitis caused by crizotinib. J Thorac Oncol. 2014;9(7):e51–3.Google Scholar
  78. 78.
    Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–77.Google Scholar
  79. 79.
    Paik PK, Arcila ME, Fara M, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011;29:2046–51.Google Scholar
  80. 80.
    Choi JN. Dermatologic adverse events to chemotherapeutic agents, part 2: BRAF inhibitors, MEK inhibitors, and ipilimumab. Semin Cutan Med Surg. 2014;33(1):40–8Google Scholar
  81. 81.
    Planchard D, Kim TM, Mazieres J, et al. Dabrafenib in patients with BRAF V600E-mutant advanced non-small cell lung cancer: a multicenter, open-label phase II trial (BRF113928). ESMO Congress. Abstract LBA38_PR. Presented September 29, 2014.Google Scholar
  82. 82.
    Rinderknecht JD, Goldinger SM, Rozati S, et al. RASopathic skin eruptions during vemurafenib therapy. PLoS One. 2013;8(3):e58721.Google Scholar
  83. 83.
    Anforth R, Blumetti TC, Clements A, et al. Systemic retinoids for the chemoprevention of cutaneous squamous cell carcinoma and verrucal keratosis in a cohort of patients on BRAF inhibitors. Br J Dermatol. 2013;169(6):1310–3.Google Scholar
  84. 84.
    Dummer R, Rinderknecht J, Goldinger SM. Ultraviolet A and photosensitivity during vemurafenib therapy. N Engl J Med. 2012;366(5):480–1.Google Scholar
  85. 85.
    Hecht M, Zimmer L, Loquai C, et al. Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients. Ann Oncol. 2015;26(6):1238–44.Google Scholar
  86. 86.
    Mossner R, Zimmer L, Berking C, et al. Erythema nodosum-like lesions during BRAF inhibitor therapy: report on 16 new cases and review of the literature. J Eur Acad Dermatol Venerol. 2015.Google Scholar
  87. 87.
    Sanlorenzo M, Choudhry A, Vujic I, et al. Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma. J Am Acad Dermatol. 2014;71(6):1102–1109.e1.Google Scholar
  88. 88.
    Chen FW, Tseng D, Reddy S, et al. Involution of eruptive melanocytic nevi on combination BRAF and MEK inhibitor therapy. JAMA Dermatol. 2014;150(11):1209–12.Google Scholar
  89. 89.
    Grosso J, Horak CE, Inzunza D, et al. Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538). 2013 ASCO Annual Meeting. J Clin Oncol. 2013;31(suppl):abstract 3016.Google Scholar
  90. 90.
    Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.Google Scholar
  91. 91.
    Rizvi NA, Mazières J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16(3):257–65.Google Scholar
  92. 92.
    Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.Google Scholar
  93. 93.
    Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.Google Scholar
  94. 94.
    Lutzky J, Antonia SJ, Blake-Haskins A. A phase 1 study of MEDI4736, an anti-PD-L1 antibody, in patients with advanced solid tumors. 2014 ASCO Annual Meeting. J Clin Oncol. 2014;32:5s (suppl; abstr 3001^).Google Scholar
  95. 95.
    Segal NH, Antonia SJ, Brahmer JR, et al. Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. 2014 ASCO Annual Meeting. J Clin Oncol. 2014;32:5s (suppl; abstr 3002^).Google Scholar
  96. 96.
    Joseph RW, Cappel M, Goedjen B. Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy. Cancer Immunol Res. 2015;3(1):18–22.Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Silvina B. Pugliese
    • 1
  • Joel W. Neal
    • 2
  • Bernice Y. Kwong
    • 1
    • 3
  1. 1.Department of DermatologyStanford UniversityStanfordUSA
  2. 2.Department of Medicine, Division of OncologyStanford University/Stanford Cancer InstituteStanfordUSA
  3. 3.Palo AltoUSA

Personalised recommendations