Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in Patients with Platinum-Resistant or Immunotherapy-Resistant Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective, Real-World Study

Kailin Chen,1 Yuyi Li,12 Xiaoyu Chen,12 Weichang Zhu,12 Yuchen Shi,12 Xu Ye,1 Cuihong Jiang,1 Yajun Li,3 Feng Liu,11Department of Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410013, People’s Republic of China; 2Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3Department of Lymphoma and Hematology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410013, People’s Republic of ChinaCorrespondence: Feng Liu, Department of Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410013, People’s Republic of China, Email liufeng@hnca.org.cn; Yajun Li, Department of Lymphoma and Hematology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410013, People’s Republic of China, Email liyajun@hnca.org.cnPurpose: For recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC) that has progressed after platinum-based chemotherapy or immunotherapy, treatment options are limited. This real-world study evaluated the effectiveness and safety of anlotinib, alone or combined with PD-1 inhibitors, in patients with platinum-resistant or PD-1 inhibitor-resistant R/M-NPC.Patients and Methods: This retrospective, single-center study included 86 patients with R/M-NPC who received at least one cycle of anlotinib-based therapy between November 2018 and March 2024. Patients were divided into anlotinib monotherapy (n=53) and anlotinib plus PD-1 blockade combination groups (n=33). The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.Results: The ORR was significantly higher in the combination group than in the monotherapy group (30.30% vs 7.55%, P=0.013). DCR was also superior with combination therapy (87.90% vs 62.30%, P=0.02). Median PFS was 8.93 months for combination therapy versus 5.13 months for monotherapy (P=0.011); median OS was 12.97 months versus 8.73 months (P=0.001), respectively. In the subgroup of patients with prior immune checkpoint inhibitor therapy, the combination regimen maintained a numerically higher ORR (50.00% vs 13.60%, P=0.028), a longer PFS (mPFS: 9.57 vs 5.12 months, P=0.036) and OS (mOS: 12.97 vs 8.23 months, P=0.009), compared to monotherapy. Treatment-related adverse events (TRAEs) occurred in 54.65% of patients, with most being grade 1– 2. Grade 3 TRAEs were reported in 6 patients; no grade 4 TRAEs or treatment-related deaths occurred.Conclusion: Anlotinib plus PD-1 blockade significantly improved antitumor activity versus monotherapy in platinum- or PD-1 inhibitor-resistant R/M NPC, with acceptable safety. The favorable trends seen in the immunotherapy-pretreated subgroup are preliminary. These findings support the further evaluation of this combination as a promising therapeutic option in this challenging patient population.Keywords: anlotinib, PD-1 inhibitor, nasopharyngeal carcinoma, platinum-resistant, immunotherapy-resistant