DISCUSSION
toxicity, nasopharyngeal necrosis, ICA rupture, necrosis, epistaxis
EPISTAXIS, RECURRENCE, NECROSIS
To our knowledge, this is the first prospective study to evaluate the antitumor activity and safety of immunotherapy combined with antiangiogenesis therapy for RM-NPC. Our results revealed that camrelizumab plus apatinib showed promising antitumor activity and a manageable toxicity profile. Nasopharyngeal necrosis was the most frequent and important cause of apatinib discontinuation and was significantly associated with nasopharyngeal recurrence and reirradiation.There are limited effective options for patients with RM-NPC who suffer from progression after first-line chemotherapy. Single-agent chemotherapy, considered a standard subsequent-line treatment, exhibited an ORR of 23.3%, with a median PFS of 5.5 months.The safety profiles of camrelizumab and apatinib in NPC were consistent with those in other solid tumorsIn the current study, nasopharyngeal necrosis and its associated severe epistaxis were key limiting factors for the long-term maintenance of apatinib. Two patients developed grade 4 necrosis with a high risk of lethal ICA rupture. Such deadly incidents have been previously reported when using anti-VEGFR TKIs in treating NPC.Moreover, we suppose that because nasopharyngeal necrosis was associated with local recurrence and limited the long-term use of apatinib, an ORR advantage for patients with locoregional recurrence could not reflect in the PFS. This is based on our results showing that patients who experienced dose reduction or discontinuation had a similar outcome with recurrent patients (higher ORR, but indistinguishable DoR and PFS), and the most common reason for dose adjustment was nasopharyngeal necrosis. Thus, we speculate that this regimen may work better for refractory recurrent patients if they could adhere to the combined treatment.The predictive value of PD-L1 expression and the TMB score for NPC were unclear. Similar to toripalimab,In addition to these notable findings, there are several limitations to consider. First, this was a single-arm study without control group, and the synergistic effect of apatinib and camrelizumab needs further validation. We are now undertaking a prospective small-sample trial to compare the treatment effects of mono-chemotherapy, chemoimmunotherapy, antiangio-immunotherapy, and antiangiochemoimmunotherapy (ClinicalTrials.gov identifier: In conclusion, camrelizumab plus apatinib showed encouraging efficacy in patients with RM-NPC. Nasopharyngeal necrosis, associated with a history of reirradiation and local recurrence, should be closely monitored and managed during treatment. Future randomized controlled trials are needed to confirm these findings.