Patient characteristics
In this retrospective study, 19 eligible patients ( 13 males and 6 females) were selected from 1,510 patients with NPC. All patients were Asian and ranged in age from 32 to 73 years, with a median age of 54 years Most of the patients were under 65 years old, accounting for 78 9% Additionally, 63.2% and 26.3% of the patients had a history of smoking and drinking, respectively. The HBV DNA baseline was positive in 10 patients (52.6%) and negative in 7 (36.8%). Non-keratinising undifferentiated NPC (WHO Type III) was the main pathological type, accounting for 63.2% and the remaining 36.8% had non-keratinising differentiated NPC (WHO Type II) Seven patients had distant metastasis (stage IVb) and the remaining 12 patients were stage IVa. Immunotherapy was used as first-line therapy in 12 patients and second-line or higher in seven patients. Additionally, 11 and eight patients underwent ≤6 cycles of immunotherapy and >6 cycles of immunotherapy, respectively. Fourteen patients received radiotherapy in combination with immunotherapy Antibiotics were administered to six patients during immunotherapy, primarily because of pneumonia and oral mucositis. HBsAg was positive in all patients prior to immunotherapy and baseline liver function was normal. Table 1 lists the clinical characteristics.
Treatment
As shown in Table 2, most patients were treated with immunotherapy in combination with radiotherapy during first-line therapy. Conventional radiotherapy was the primary mode of radiotherapy, whereas Stereotactic Body Radiation Therapy was only applied to a few metastatic lesions. Five patients received Sintilimab, four received Nivolumab, three received Camrelizumab, three received Toripalimab, three received Penpulimab and one received Pembrolizumab The 12th patient was first diagnosed with NPC in August 2013 and underwent systemic chemoradiotherapy; unfortunately, it relapsed 2 years later. In September 2018, he started Camrelizumab combined with radiotherapy after receiving multiple lines of treatment that failed. This regimen was the sixth line of treatment for the patient, which maintained PFS for 6.0 months before the disease progressed again. The 14th patient was treated with Sintilimab in combination with radiotherapy as a fourth-line treatment after failing multiple lines of treatment, which maintained PFS for up to 16.0 months. Of the HBV patients, 13 patients and one patient were treated with Entecavir and Tenofovir, respectively. The remaining five patients refused to receive regular anti-HBV treatment regimented by infectious disease doctors because there were no significant abnormalities in liver function and no significant increase in HBV DNA
Safety
Table 3 lists the treatment-related AEs. None of the patients in the study experienced HBV reactivation or treatment-related death. All patients had at least grade 1 adverse reactions, whereas the main adverse reactions included hypoerythrocytopia, anaemia, hypoproteinaemia and increased conjugated bilirubin. The adverse reactions were generally mild (grade 1) and only leukopenia, lymphocytopenia, thrombocytopenia, neutrophilia, increased ALT and increased AST were grade 3. In the 7th and 11th cases, although ALT and AST increased significantly after treatment, HBV reactivation did not occur; thus, it was considered to be caused by chemotherapy and radiotherapy Immune treatment-related adverse reactions, such as hypothyroidism, fever, root and rash were all grade 1. Therefore, the ICIs were well-tolerated in NPC patients with HBV infection.
Tumour response
Among the 19 patients, 18 were evaluated for tumour response as one patient lacked post-treatment imaging data. Table 2 presents in detail the tumour response data. Three patients ( 16.7%) achieved a complete response, 11 patients (61. 1%) had a partial response, two patients ( 11. 1%) had stable disease and two patients ( 11. 1%) had progressive disease. The objective response rate was 77.8% and the disease control rate was 88.9%.
Survival outcome
The median number of ICI cycles was 6 (range, 1– 18 cycles). The median follow-up time was 19.6 months (range, 3.3–42.5 months). The median OS of all patients was 14.4 months, and the median PFS was 10.4 months The 1-year PFS and 1-year OS were 47 4% and 52.6%, respectively Figure 1A and Figure 1B show the survival curves.
Subgroup analysis
Subgroup analysis was conducted for the PFS and OS of all the patients in the study (Table 4). Immunotherapy as a first-line treatment for nasopharyngeal cancer increased OS (HR = 0.095, 95%CI: 0.001–0.831, P = 0.033) but did not prolong PFS (P = 0.204). Additionally, no significant difference in OS and PFS was found with respect to gender, age, whether anti-HBV treatment was administered, whether combined radiotherapy was administered, whether antibiotics were used or the number of ICI cycles.