Department of Hematology-Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Cancer Med. 2024 Jun;13(12):e7257. doi: 10.1002/cam4.7257.
Both immunotherapy (IO) and targeted therapy (TT) are used as adjuvant (adj) treatment for stage III melanoma, however, data describing real-world outcomes are limited. In addition, a significant proportion of patients relapse, for whom best management is unclear. The aim of our study was to assess the efficacy, and safety of adj anti-PD1 IO and TT in a real-world cohort of patients with resected stage III melanoma, and further delineate patterns of recurrence and treatment strategies.
We retrospectively analyzed 130 patients who received adj therapy (100 anti-PD1 IO and 30 TT).
At a median follow-up of 30 months, median relapse-free survival (RFS) was 24.6 (95% CI, 17-not reached [NR]) versus 64 (95% CI, 29.5-NR) months for the TT and IO groups, respectively (p = 0.26). Median overall survival (OS) was NR for either subgroup. At data cutoff, 77% and 82% of patients in TT and IO arms were alive. A higher number of grade ≥3 treatment-related adverse events (AEs) were noted in the IO group (11% vs. 3%), however, a higher proportion of patients permanently discontinued adj therapy in the TT group (43% vs. 11%) due to toxicity. Strategies at relapse and outcomes were variable based on location and timing of recurrence. A significant number of patients who relapsed after adj IO received a second round of IO. Among them, patients who were off adj IO at relapse had superior second median RFS (mRFS2), compared to those who relapsed while on adj IO; mRFS2 was NR versus 5.1 months (95% CI, 2.5-NR), respectively, p = 0.02.
In summary, both TT and IO yielded prolonged RFS in a real-world setting, however, longer follow-up is needed to determine any potential OS benefit. Adj therapy, particularly TT, may not be as well tolerated as suggested in clinical trials, with lower completion rates (59% vs. 74%) in a real-life setting. Overall, patients who relapse during adj therapy have poor outcomes, while patients who relapse after discontinuation of adj IO therapy appear to benefit from IO re-treatment.
免疫疗法 (IO) 和靶向治疗 (TT) 均被用作 III 期黑色素瘤的辅助 (adj) 治疗，但描述真实世界结果的数据有限。此外，相当一部分患者复发，其最佳治疗方法尚不清楚。我们研究的目的是评估在接受辅助治疗的 III 期黑色素瘤患者的真实世界队列中，抗 PD1 IO 和 TT 的疗效和安全性，并进一步阐明复发模式和治疗策略。
我们回顾性分析了 130 例接受辅助治疗 (100 例抗 PD1 IO 和 30 例 TT) 的患者。
在中位随访 30 个月时，TT 组和 IO 组的中位无复发生存期 (RFS) 分别为 24.6 (95%CI，17-NR) 和 64 (95%CI，29.5-NR) 个月（p=0.26）。两组的中位总生存期 (OS) 均未达到 NR。截止数据时，TT 组和 IO 组分别有 77%和 82%的患者存活。IO 组的治疗相关不良事件 (AE) 发生率更高（11% 比 3%），但 TT 组因毒性而永久停止辅助治疗的患者比例更高（43% 比 11%）。基于复发的位置和时间，复发后的治疗策略和结果存在差异。相当一部分接受辅助 IO 治疗后复发的患者接受了第二轮 IO 治疗。在这些患者中，复发时已停用辅助 IO 的患者的中位第二次无复发生存期 (mRFS2) 优于复发时仍在接受辅助 IO 治疗的患者；mRFS2 分别为 NR 与 5.1 个月（95%CI，2.5-NR），p=0.02。
总之，TT 和 IO 在真实环境中均延长了 RFS，但需要更长的随访时间来确定任何潜在的 OS 获益。辅助治疗，特别是 TT，在真实环境中的完成率较低（59%比 74%），可能不如临床试验中耐受良好。总体而言，辅助治疗期间复发的患者预后较差，而辅助 IO 治疗停止后复发的患者似乎从 IO 再治疗中获益。
