Gupta Amol, De Jesus-Acosta Ana, Zheng Lei, Lee Valerie, Kamel Ihab, Le Dung, Pishvaian Michael, Laheru Daniel
The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, MD, United States.
Front Oncol. 2023 Aug 28;13:1250136. doi: 10.3389/fonc.2023.1250136. eCollection 2023.
The efficacy of combination chemotherapy beyond the first-line setting remains modest in patients with advanced pancreatic adenocarcinoma (PAC). Evidence from recent clinical studies has shown that liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) resulted in survival benefits in patients with advanced pancreatic adenocarcinoma (APAC) after progression on gemcitabine-based treatment. However, the survival benefits of nal-IRI in the third and later lines, in which limited options are available, have yet to be extensively studied. Also, some studies have shown conflicting results regarding the impact of prior treatment with conventional IRI on patient outcomes following treatment with nal-IRI. Therefore, this real-world study aimed to evaluate the efficacy and safety of nal-IRI plus 5FU-LV in advanced PAC patients who progressed on conventional IRI-containing regimens.
A retrospective chart review was conducted between November 2016 to December 2022 on 30 patients diagnosed with advanced PAC who completed at least one cycle of nal-IRI plus 5-FU- LV and were previously treated with conventional IRI. Data regarding survival outcomes were retrieved.
Thirty patients met the inclusion criteria. Overall, 76.7% of the patients received at least two lines of therapy prior to nal-IRI. The median overall duration of nal-IRI treatment was 2.0 months (IQR: 1.3 - 3.9 months). One patient (3.3%) had a partial response, and seven patients (23.3%) had stable disease as their best response. The median progression-free survival (PFS) was 1.9 months (95% CI 1.6 - 2.0) and the 6-month PFS rate was 20.0%. The median overall survival (OS) was 5.0 months (95% CI 3.4 - 7.0), and the 6-month OS rate was 36.7%. An interval between conventional IRI and nal-IRI ≥5.5 months was significantly associated with prolonged OS of 10.2 months (95% CI 3.3 - 12.1) versus 4.3 months (95% CI 2.1 - 5.9; p =0.003). Ten patients (33.3%) experienced grade 3 adverse events, most commonly nausea, fatigue, diarrhea, and non-neutropenic fever.
Nal-IRI plus 5FU/LV had modest survival benefits and an acceptable safety profile in patients with prior conventional IRI. A longer interval between conventional IRI and nal-IRI was associated with increased survival outcomes.
对于晚期胰腺腺癌（PAC）患者，一线治疗后的联合化疗疗效仍较为有限。近期临床研究证据表明，脂质体伊立替康（nal-IRI）联合5-氟尿嘧啶（5-FU）和亚叶酸钙（LV）可使接受基于吉西他滨治疗后病情进展的晚期胰腺腺癌（APAC）患者获益。然而，nal-IRI在三线及更后线治疗中的生存获益（此时可用选择有限）尚未得到广泛研究。此外，一些研究对于既往使用传统伊立替康（IRI）治疗对患者接受nal-IRI治疗后结局的影响得出了相互矛盾的结果。因此，本项真实世界研究旨在评估nal-IRI联合5FU-LV在接受含传统IRI方案治疗后病情进展的晚期PAC患者中的疗效和安全性。
对2016年11月至2022年12月期间确诊为晚期PAC且完成至少一个周期nal-IRI联合5-FU-LV治疗并曾接受传统IRI治疗的30例患者进行回顾性病历审查。检索生存结局相关数据。
30例患者符合纳入标准。总体而言，76.7%的患者在接受nal-IRI治疗前至少接受过两线治疗。nal-IRI治疗的中位总疗程为2.0个月（四分位间距：1.3 - 3.9个月）。1例患者（3.3%）出现部分缓解，7例患者（23.3%）最佳缓解为病情稳定。中位无进展生存期（PFS）为1.9个月（95%置信区间1.6 - 2.0），6个月PFS率为20.0%。中位总生存期（OS）为5.0个月（95%置信区间3.4 - 7.0），6个月OS率为36.7%。传统IRI与nal-IRI之间的间隔≥5.5个月与OS延长显著相关，分别为10.2个月（95%置信区间3.3 - 12.1）和4.3个月（95%置信区间2.1 - 5.9；p =0.003）。10例患者（33.3%）发生3级不良事件，最常见的是恶心、疲劳、腹泻和非中性粒细胞减少性发热。
对于既往接受传统IRI治疗的患者，nal-IRI联合5FU/LV有一定的生存获益且安全性可接受。传统IRI与nal-IRI之间间隔较长与生存结局改善相关。
