Advanced vulvar cancer is associated with a very poor prognosis. Surgical resection is the mainstay of treatment, with radiation indicated for areas at high risk for recurrence. When surgical and radiation options have been exhausted, the effectiveness of systemic chemotherapy is poor. No biologic or targeted agents have been approved for the management of advanced or recurrent vulvar cancer. Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), has been successfully used as a target of tumor immune therapy in small cell lung cancer and melanoma. We present the first case in the literature of a patient with recurrent vulvar cancer who was treated successfully with pembrolizumab. Caris next-generation testing revealed a PD-L1 and PD-1 mutation (PD-L1 positive, 2+, 100%). She attained a complete clinical remission after 2 cycles, and a CT scan after 6 cycles revealed a significant response by RECIST criteria. After completing 10 cycles, treatment was stopped due to complications of severe malnutrition related to narcotic abuse. A CT scan 10 weeks after the final treatment revealed no adenopathy. Pembrolizumab is a safe and effective chemotherapeutic agent to treat recurrent vulvar carcinoma.

National Cancer Institute: SEER Cancer Statistics Factsheets: Vulvar Cancer. (accessed June 6, 2018).
Alkatout I, Schubert M, Garbrecht N, Weigel MT, Jonat W, Mundhenke C, Gunther V: Vulvar cancer: epidemiology, clinical presentation, and management options. Int J Womens Health 2015; 7: 305–313.
Ueda Y, Enomoto T, Kimura T, Yoshino K, Fujita M, Kimura T: Two distinct pathways to development of squamous cell carcinoma of the vulva. J Skin Cancer 2011; 2011: 951250.
Sul J, Blumenthal GM, Jiang X, He K, Keegan P, Pazdur R: FDA approval summary: pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1. Oncologist 2016; 21: 643–650.
Hacker NF, Berek JS, Lagasse LD, Nieberg RK, Leuchter RS: Individualization of treatment for stage I squamous cell vulvar carcinoma. Obstet Gynecol 1984; 63: 155–162.
Hoffman JS, Kumar NB, Morley GW: Microinvasive squamous carcinoma of the vulva: search for a definition. Obstet Gynecol 1983; 61: 615–618.
Tilmans AS, Sutton GP, Look KY, Stehman FB, Ehrlich CE, Hornback NB: Recurrent squamous carcinoma of the vulva. Am J Obstet Gynecol 1992; 167: 1383–1389.
Nooij LS, Brand FA, Gaarenstroom KN, Creutzberg CL, de Hullu JA, van Poelgeest MI: Risk factors and treatment for recurrent vulvar squamous cell carcinoma. Crit Rev Oncol Hematol 2016; 106: 1–13.
Belinson JL, Stewart JA, Richards AL, McClure M: Bleomycin, vincristine, mitomycin-C, and cisplatin in the management of gynecological squamous cell carcinomas. Gynecol Oncol 1985; 20: 387–393.
Cormio G, Loizzi V, Gissi F, Serrati G, Panzarino M, Carriero C, Selvaggi L: Cisplatin and vinorelbine chemotherapy in recurrent vulvar carcinoma. Oncology 2009; 77: 281–284.
Han SN, Vergote I, Amant F: Weekly paclitaxel/carboplatin in the treatment of locally advanced, recurrent, or metastatic vulvar cancer. Int J Gynecol Cancer 2012; 22: 865–868.
Muss HB, Bundy BN, Christopherson WA: Mitoxantrone in the treatment of advanced vulvar and vaginal carcinoma. A gynecologic oncology group study. Am J Clin Oncol 1989; 12: 142–144.
Thigpen JT, Blessing JA, Homesley HD, Lewis GC Jr: Phase II trials of cisplatin and piperazinedione in advanced or recurrent squamous cell carcinoma of the vulva: a Gynecologic Oncology Group Study. Gynecol Oncol 1986; 23: 358–363.
Trope C, Johnsson JE, Larsson G, Simonsen E: Bleomycin alone or combined with mitomycin C in treatment of advanced or recurrent squamous cell carcinoma of the vulva. Cancer Treat Rep 1980; 64: 639–642.
Wagenaar HC, Colombo N, Vergote I, Hoctin-Boes G, Zanetta G, Pecorelli S, Lacave AJ, van Hoesel Q, Cervantes A, Bolis G, Namer M, Lhomme C, Guastalla JP, Nooij MA, Poveda A, Scotto di Palumbo V, Vermorken JB: Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer. Gynecol Oncol 2001; 81: 348–354.
Witteveen PO, van der Velden J, Vergote I, Guerra C, Scarabeli C, Coens C, Demonty G, Reed N: Phase II study on paclitaxel in patients with recurrent, metastatic or locally advanced vulvar cancer not amenable to surgery or radiotherapy: a study of the EORTC-GCG (European Organisation for Research and Treatment of Cancer – Gynaecological Cancer Group). Ann Oncol 2009; 20: 1511–1516.
Clancy AA, Spaans JN, Weberpals JI: The forgotten woman’s cancer: vulvar squamous cell carcinoma (VSCC) and a targeted approach to therapy. Ann Oncol 2016; 27: 1696–1705.
Palisoul ML, Mullen MM, Feldman R, Thaker PH: Identification of molecular targets in vulvar cancers. Gynecol Oncol 2017; 146: 305–313.
Horowitz NS, Olawaiye AB, Borger DR, Growdon WB, Krasner CN, Matulonis UA, Liu JF, Lee J, Brard L, Dizon DS: Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva. Gynecol Oncol 2012; 127: 141–146.
Bergstrom J, Bidus M, Miles E, Allard J: Use of cetuximab in combination with cisplatin and adjuvant pelvic radiation for stage IIIB vulvar carcinoma. Case Rep Obstet Gynecol 2015; 2015: 139817.
Butler JS, Milliken DA, Dina R, Eccles SA, Maghami SG, Jameson C, Mason P, Shepherd JH, Soutter WP, Barton DP: Isolated groin recurrence in vulval squamous cell cancer (VSCC). The importance of node count. Eur J Gynaecol Oncol 2010; 31: 510–513.
Cormio G, Loizzi V, Carriero C, Cazzolla A, Putignano G, Selvaggi L: Groin recurrence in carcinoma of the vulva: management and outcome. Eur J Cancer Care (Engl) 2010; 19: 302–307.
Gordinier ME, Malpica A, Burke TW, Bodurka DC, Wolf JK, Jhingran A, Ramirez PT, Levenback C: Groin recurrence in patients with vulvar cancer with negative nodes on superficial inguinal lymphadenectomy. Gynecol Oncol 2003; 90: 625–628.
Klapdor R, Hertel H, Soergel P, Hillemanns P: Groin recurrences in node negative vulvar cancer patients after sole sentinel lymph node dissection. Int J Gynecol Cancer 2017; 27: 166–170.
van Beekhuizen HJ, Auzin M, van den Einden LC, de Hullu JA, van der Velden J, Wildhagen MF, van Doorn HC: Lymph node count at inguinofemoral lymphadenectomy and groin recurrences in vulvar cancer. Int J Gynecol Cancer 2014; 24: 773–778.
Abdel-Rahman O: Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Immunotherapy 2016; 8: 1383–1391.
Brahmer JR, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M: Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol 2017; 18: 1600–1609.
Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM: Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol 2017; 35: 3823–3829.
Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR: Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375: 1823–1833.
Petrella TM, Robert C, Richtig E, Miller WH Jr, Masucci GV, Walpole E, Lebbe C, Steven N, Middleton MR, Hille D, Zhou W, Ibrahim N, Cebon J: Patient-reported outcomes in KEYNOTE-006, a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma. Eur J Cancer 2017; 86: 115–124.
Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, van Brummelen E: Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol 2017; 18: 623–630.
Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz CH: Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol 2016; 34: 3733–3739.
Chan TS, Luk TH, Lau JS, Khong PL, Kwong YL: Low-dose pembrolizumab for relapsed/refractory Hodgkin lymphoma: high efficacy with minimal toxicity. Ann Hematol 2017; 96: 647–651.
Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von TB, Shipp MA, Zhang Y, Ricart AD, Balakumaran A, Moskowitz CH: Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 2017; 35: 2125–2132.
Balar AV, Castellano D, O'Donnell PH, Grivas P, Vuky J, Powles T, Plimack ER, Hahn NM, de WR, Pang L, Savage MJ, Perini RF, Keefe SM, Bajorin D, Bellmunt J: First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017; 18: 1483–1492.
Plimack ER, Bellmunt J, Gupta S, Berger R, Chow LQ, Juco J, Lunceford J, Saraf S, Perini RF, O’Donnell PH: Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study. Lancet Oncol 2017; 18: 212–220.
Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L: Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol 2016; 34: 2460–2467.
Blumenthal DT, Yalon M, Vainer GW, Lossos A, Yust S, Tzach L, Cagnano E, Limon D, Bokstein F: Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors. J Neurooncol 2016; 129: 453–460.
Frenel JS, Le TC, O'Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, van Brummelen EMJ, Rugo HS, Thomas S, Saraf S, Rangwala R, Varga A: Safety and efficacy of pembrolizumab in advanced, programmed death ligand 1-positive cervical cancer: results from the phase Ib KEYNOTE-028 trial. J Clin Oncol 2017; 35: 4035–4041.
Mehnert JM, Panda A, Zhong H, Hirshfield K, Damare S, Lane K, Sokol L, Stein MN, Rodriguez-Rodriquez L, Kaufman HL, Ali S, Ross JS, Pavlick DC, Bhanot G, White EP, DiPaola RS, Lovell A, Cheng J, Ganesan S: Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer. J Clin Invest 2016; 126: 2334–2340.
Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, Puzanov I, Mehnert JM, Aung KL, Lopez J, Carrigan M, Saraf S, Chen M, Soria JC: Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol 2017; 35: 2535–2541.
Ghorani E, Kaur B, Fisher RA, Short D, Joneborg U, Carlson JW, Akarca A, Marafioti T, Quezada SA, Sarwar N, Seckl MJ: Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia. Lancet 2017; 390: 2343–2345.
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