Treatment and assessments
toxicity
DISEASE PROGRESSION, ADVERSE EVENT, HYPERPROGRESSION, ADVERSE EVENTS, MAY, TUMOR GROWTH
All patients received camrelizumab 200 mg intravenously every 2 weeks and apatinib 500 mg orally once daily, 4 weeks as a cycle, until disease progression, unacceptable toxicity, or withdrawal of consent. Dose delay or reduction of apatinib (to 250 mg) was allowed. Dose delay for camrelizumab was allowed, and dose modification was not allowed. The maximum duration of dose delay was 8 weeks for camrelizumab and 4 weeks for apatinib. If the length of the dose delay exceeded the maximum duration, the treatment agent was discontinued. However, during initial treatment, more than two-thirds of patients experienced dose reduction or discontinuation due to apatinib-related adverse events (AEs). Therefore, the study protocol was amended to version 1.1 on May 18, 2020, and the starting dose of apatinib was set to 250 mg.The response evaluation was performed according to Lugano 2014 response criteria. For the response evaluation, positron emission tomography-computed tomography (PET-CT) was recommended, while CT was allowed upon the patient’s request. Imaging assessment was performed every 8 weeks for the first 6 months, every 12 weeks from 6 months to 12 months, and every 16 weeks thereafter until disease progression or the end of study. Hyperprogression was defined as a tumor growth rate at the first assessment that is equal to or greater than twice the baseline. The safety records of this study included clinical symptoms, vital signs, physical examination, and laboratory tests. All AEs were monitored and documented until 90 days after the last dose. The grading of AEs was performed according to the Common Terminology Criteria for Adverse Events, version 4.03.