Safety
hyperplasia, thrombocytopenia, myocarditis, rash, nasopharyngeal necrosis, necrosis, hypertension, hand and foot syndrome
PATHOLOGY, HYPERPLASIA, ADVERSE EVENTS, THROMBOCYTOPENIA, MYOCARDITIS, HAND-FOOT SYNDROME, NECROSIS, EVENTS, HYPERTENSION
In the safety set, dose reductions occurred in 49 (68.1%) of 72 patients for apatinib, of whom 39 (79.6%) patients required only one level of dose reduction and 17 (34.7%) patients had two levels of dose reduction. Treatment-related adverse events led to dose interruptions of apatinib in 49 (68.1%) of 72 patients, and of camrelizumab in 15 (20.8%) patients. The most common reasons for interruptions of apatinib were hypertension (19 [38.8%]), hand and foot syndrome (15 [30.6%]), increased aspartate aminotransferase (nine [18.4%]), and increased alanine aminotransferase (eight [16.3%]); similarly, increased aspartate aminotransferase (nine [18.4%]) and increased alanine aminotransferase (eight [16.3%]) led to camrelizumab interruptions. Nine patients discontinued apatinib because of nasopharyngeal necrosis (seven [77.8%]), increased alkaline phosphatase (one [11.1%]), and thrombocytopenia (one [11.1%]). Three patients discontinued camrelizumab because of rash (two [66.7%]) and immune myocarditis (one [33.3%]).The most common grade 3–4 adverse events were hypertension (27.8%), hand-foot syndrome (12.5%), and the increase in AST (11.1%). Serious adverse events were reported in three patients, with two presenting with rash, and one with acute immune myocarditis, all of which were considered treatment-related. In nine (12.5%) of patients, receptive cutaneous slender endothelial multiplication (RCCEP), a common and self-limiting trAE of camrelizumab, was observed, with two individuals revealing grade 3 events. RCCEP occurred only on the skin, with pathology revealing hairlike endothelial hyperplasia and slender hyperplasia in the dermis. During the treatment period, we saw the occurrence of nasopharyngeal necrosis in 9 cases (12.5%) and the diagnosis for all cases of nasopharyngeal necrosis was confirmed through nasopharyngoscope and/or magnetic resonance imaging. All nine patients with nasopharyngeal necrosis were classified as grade 3 or higher (Supplementary Table 