Keywords
nasopharyngeal carcinoma - immunotherapy - nasopharynx - head and neck cancer - EBV - immune checkpoint inhibitors - recurrent disease - adoptive cell therapy
Case Presentation
A 60-year-old female presented with T2N0M0 nonkeratinizing Epstein–Barr virus (EBV) negative squamous cell carcinoma of the left nasopharynx (nasopharyngeal carcinoma [NPC]). She underwent 6 weeks of chemoradiation with cisplatin. Posttreatment positron emission tomography/computed tomography (PET/CT) illustrated cervical lymphadenopathy and persistent disease in the nasopharynx ([Fig. 1]). Biopsy of cervical nodal uptake confirmed persistent disease. Thus, left neck dissection was performed. She was then referred to our center for endoscopic endonasal resection and craniotomy with carotid resection/bypass. Surgical margins were negative. However, 7-month posttreatment PET/CT illustrated residual disease, which was confirmed on biopsy ([Fig. 2]). She started pembrolizumab and experienced interval improvement over the course of 8 months. She then completed four cycles of gemcitabine/cisplatin (GP). Due to persistent disease, she continued pembrolizumab and started capecitabine as well. Given disease progression, lenvatinib was added in lieu of capecitabine. She remains on pembrolizumab and lenvatinib 3 years since initial diagnosis with stable disease.
Fig. 1 Magnetic resonance imaging (MRI) throughout treatment course: presurgical, postsurgical, 3 months postsurgery, and 6 months postsurgery. (A) Presurgical MRI. (B) Postoperative MRI. (C) Three months postoperative MRI. (D) Six months postoperative MRI illustrating recurrence in the left nasopharynx.
Fig. 2 Positron emission tomography/computed tomography (PET/CT) scan imaging illustrating recurrence postsurgery and immunotherapy treatment response. (A) PET/CT illustrating recurrence postsurgery. Six months PET/CT illustrating complete response to pembrolizumab.
Literature Review
Radiation therapy serves as the mainstay of treatment for NPC in early-stage disease while concurrent chemoradiation is the basis for locoregional advanced disease with 80% five-year survival rate.[1]
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[6] Approximately 15% of patients experience recurrent or metastatic disease.[3]
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[6] Locoregional recurrence may prompt surgical intervention.[1]
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[8] Recurrence or metastasis pose treatment challenges as reirradiation, repeat chemotherapy, and surgery are associated with treatment toxicity and morbidity.[1]
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Immunotherapy is reserved for nonresectable recurrent or metastatic disease.[10] Current strategies include immune checkpoint inhibitors, EBV-directed vaccination, and adoptive T cell therapy.[1]
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The immunosuppressive NPC tumor microenvironment boasts an overexpression of inhibitory immune checkpoints, an ideal target for immune checkpoint inhibitors (ICIs).[1]
[10] Clinical trials have investigated the efficacy of anti-programmed cell death protein 1 (PD-1) antibodies such as pembrolizumab, nivolumab, and camrelizumab with promising results.[11]
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[13] The KEYNOTE-028 trial investigated the efficacy of pembrolizumab in unresectable recurrences revealing a 26% objective response rate (ORR) and 33% one-year progression-free survival (PFS).[11] However, the KEYNOTE-122, phase III trial illustrated that pembrolizumab did not improve PFS or ORR compared with chemotherapy.[14] A phase II trial assessing nivolumab response in recurrent or metastatic NPC noted a 20% ORR with 59% one-year overall survival (OS).[12] Two single-arm phase I trials evaluated camrelizumab as (1) monotherapy in recurrence or metastasis with a 34% ORR and 27% one-year PFS and (2) combined with GP in patients with recurrence or metastasis disease yielding a 91% ORR and 61% PFS.[1]
[13] The JUPITER-02 trial assessed the efficacy of toripalimab combined with GP versus placebo and GP, revealing 49.4% of patients in the combination arm experienced PFS, compared with 27.9% in the control arm.[15]
[16] A meta-analysis of ICIs noted 27% ORR and 61% OS.[17]
EBV-directed vaccination offers preventative and therapeutic strategies against infection with EBV, a key contributor to the pathogenesis of NPC.[18] Previous clinical trials investigated peptide and viral vaccines by targeting EBV glycoproteins: gH/gL and gB, membrane proteins critical for epithelial cell infection, and virus-like proteins target antigens such as latent membrane protein 1 (LMP1) or LMP2, key drivers in malignant transformation of EBV-infected cells.[18]
[19] A phase I trial noted partial clinical response in advanced EBV-associated NPC.[19]
Ultimately, treatment of recurrent or metastatic NPC remains complex and requires a multifaceted approach. The advent of immunotherapy, primarily anti-PD-1 antibodies, as novel treatment for recurrent or metastatic NPC has provided an additional treatment option. Although clinical trials have illustrated promising results, long-term follow-up studies are necessary.
