DISCUSSION
NSCLC, hypoxia, tumor, extracranial lesions
TUMOR, INFILTRATION, HYPOXIA, DISEASE, BRAIN METASTASES, RECRUITMENT, NSCLC
To our knowledge, this is the first study to report the efficacy and safety of sintilimab plus anlotinib in pretreated patients with advanced NSCLC harboring uncommon Previous studies in NSCLC have revealed the effectiveness of combined treatment with ICIs and antiangiogenic therapies. The inhibition of angiogenesis potentiates PD‐1/PD‐L1 blockade by reducing hypoxia, promoting the infiltration of CD8 T cells, and inhibiting recruitment of tumor‐associated macrophages.In the current study, 38.1% of patients who received late‐line treatment with sintilimab plus anlotinib achieved an objective response, and 85.7% achieved disease control. Overall, the median PFS was 7.0 months, and median OS was 20.0 months. Interestingly, given the diverse clinical settings, the ORR for sintilimab plus anlotinib observed in the present study (38.1%) compares favorably with previous studies of anlotinib monotherapy (9.2%)While anti‐tumor activity was observed across multiple subgroups in this study, we noted a trend towards higher ORR for patients harboring Among the nine patients with brain metastases at baseline, those with brain metastases had a similar overall PFS to those without brain metastases. Although only two patients had evaluable brain lesions, one achieved intracranial PR and one achieved intracranial SD. Both patients sustained intracranial benefit when extracranial lesions showed progression. The intracranial responses observed were active, although this requires further validation in larger patient cohorts.In this study, we evaluated the association between survival outcomes and tumor PD‐L1 expression and immune‐cell infiltration. Our results suggest that PFS and OS following treatment with sintilimab combined with anlotinib are not affected by PD‐L1 status, in line with prior studies of ICIs combined with antiangiogenic agents in patients with metastatic NSCLC.Combined treatment with sintilimab plus anlotinib was generally well tolerated, and the safety profile was consistent with that of either drug as monotherapy.Limitations of this study include its single‐arm design with a relatively small sample size and a potential for selection bias due to the lack of a control group. In addition, immunohistochemistry results could not be obtained from every patient due to sample accessibility, and there were variable tumor tissue resources. Therefore, the observed trend toward better response among patients with dual expression of PD‐L1/CD8 requires further prospective research for verification.