Discussion
tumor, cancers, bleeding
ADVERSE REACTIONS, TUMOR, INFILTRATION, CANCERS, BLEEDING, ADVERSE EVENTS
In this multicenter, single-arm, phase II, prospective clinical trial, we reported the efficacy and safety of the VEGFR2-targeting apatinib combined with PD-1 inhibitor camrelizumab in patients with RM-NPC. Our findings revealed that the ORR of patients with RM-NPC treated with apatinib plus camrelizumab was 38.5% (10/26), the DCR was 61.5% (16/26), the mPFS was 6 months, and mOS was 14 months. Apatinib plus camrelizumab was well tolerated in patients with advanced NPC, regardless of their PD-L1 status, showing good ORR and PFS. Most treatment-related adverse events could be controlled by suspending apatinib and/or camrelizumab, or taking other drugs.After receiving first-line chemotherapy, patients with RM-NPC who progress have few treatment alternatives. In the previous phase 1b KEYNOTE-028((NCT02054806) trial,(Studies by Huang et al. found that the ORR of apatinib monotherapy in patients with RM-NPC was 31.4%, the mPFS was 3.9 months, and mOS was 5.8 months. (In our previous study (NCT03130270), apatinib at 500 mg/day was used as the initial dosage for all patients, as opposed to 250 mg/day in the current study.(Anti-angiogenic therapy can boost sensitivity to anti-PD-1/PD-L1 therapy by increasing PD-L1 expression and the infiltration of CD8+T cells into the tumor microenvironment, according to preclinical research.(Currently, scant investigations exist pertaining to the amalgamation of apatinib and camrelizumab in the therapeutic intervention of RM-NPC. A recent Phase II clinical study conducted by Ding et al. showed that the coadministration of apatinib and camrelizumab yielded an ORR of 65.5% and a DCR of 86.2% for RM-NPC.(In this study, the observed adverse reactions were generally mild (23.6% grade 3–4 adverse events), and was similar to the results for apatinib combined with camrelizumab in other cancers.(This study has a number of limitations. First, the small number of patients included made it less likely that the effectiveness observed was indeed successful, hence the results for anti-tumor activity were at the preliminary stage. Second, the patients had an ECOG performance status of 0-1 from southern China, which suggests that a selected population was enrolled in the study. Therefore, a further study would be needed to investigate the efficacy of this combination for non-Chiness patients with RM-NPC. Third, we excluded patients with tumor infiltration into major blood vessels from the study cohort to reduce the risk of bleeding during treatment. In subsequent studies, we will continue to focus on evaluating the post-treatment bleeding susceptibility of patients. Fourth, this was a single-arm study with no control group for comparison, and thus selection bias could not be ruled out.