Keane Fergus, O'Connor Catherine, Moss Drew, Chou Joanne F, Perry Maria A, Crowley Fionnuala, Saxena Parima, Chan Amelia, Schoenfeld Joshua D, Singhal Anupriya, Park Wungki, Cowzer Darren, Harrold Emily, Varghese Anna M, El Dika Imane, Crane Christopher, Harding James J, Abou-Alfa Ghassan K, Kingham T Peter, Wei Alice C, Yu Kenneth H, D'Angelica Michael I, Balachandran Vinod P, Drebin Jeffrey, Jarnagin William R, Bandlamudi Chaitanya, Kelsen David, Capanu Marinela, Soares Kevin C, Balogun Fiyinfolu, O'Reilly Eileen M
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
J Natl Cancer Inst. 2025 Mar 1;117(3):496-506. doi: 10.1093/jnci/djae269.
Adjuvant modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). Data are limited on adjuvant modified FOLFIRINOX outcomes outside clinical trials.
We queried institutional databases to identify patients with resected PDAC who received 1 or more doses of adjuvant modified FOLFIRINOX. Primary endpoints were recurrence-free survival (RFS) and overall survival. Secondary endpoints were clinical factors and genomic features associated with outcomes. We estimated RFS and overall survival by using the Kaplan-Meier method. A Cox proportional hazards regression model was used to associate clinicogenomic features with survival outcomes.
A search revealed 147 individuals with PDAC between January 2015 and January 2023. Median patient age was 67 years, with 57 (39%) patients older than 70 years. Unfavorable prognostic features included 52 (36%) patients with N2 nodal status, 115 (78%) patients with lymphovascular invasion, and 133 (90%) patients with perineural invasion. Median time from surgery to initiation of modified FOLFIRINOX was 1.78 months (IQR = 1.45-2.12). In total, 124 (84%) patients completed 12 doses; 98 (67%) patients stopped oxaliplatin early because of neuropathy (median = 10 doses, range = 4-12 doses). Further dosing characteristics are summarized in Table S3, with a median follow-up of 35.1 months, a median RFS of 26 months (95% confidence interval [CI] = 19 to 39), and a median overall survival not reached. For the cohort older than 70 years of age, the median RFS was 23 months (95% CI = 14 to not reached) and the median overall survival was 51 months (95% CI = 37 to not reached). Modified FOLFIRINOX started sooner than 8 weeks from resection was associated with improved RFS (hazard ratio = 0.62, 95% CI = 0.41 to 0.96; P = .033) and overall survival (hazard ratio = 0.53, 95% CI = 0.3 to 0.94; P = .030). KRAS variation and whole-genome doubling trended to shorter RFS and overall survival. Homologous recombination deficiency status did not confer improved survival outcomes.
Adjuvant modified FOLFIRINOX was effective and tolerated in patients with resected PDAC in a nontrial setting, including for patients older than 70 years of age.
辅助性改良亚叶酸钙、氟尿嘧啶、盐酸伊立替康和奥沙利铂（FOLFIRINOX）方案是适合接受过胰腺导管腺癌（PDAC）切除术患者的标准治疗方案。临床试验以外的辅助性改良FOLFIRINOX方案治疗效果的数据有限。
我们查询机构数据库，以确定接受过1剂或更多剂辅助性改良FOLFIRINOX方案治疗的PDAC切除患者。主要终点为无复发生存期（RFS）和总生存期。次要终点为与治疗结果相关的临床因素和基因组特征。我们采用Kaplan-Meier法估计RFS和总生存期。使用Cox比例风险回归模型将临床基因组特征与生存结果相关联。
一项检索发现，2015年1月至2023年1月期间有147例PDAC患者。患者中位年龄为67岁，其中57例（39%）患者年龄超过70岁。不良预后特征包括52例（36%）N2淋巴结状态患者、115例（78%）有脉管侵犯患者和133例（90%）有神经周围侵犯患者。从手术到开始改良FOLFIRINOX方案的中位时间为1.78个月（四分位间距[IQR]=1.45-2.12）。总共124例（84%）患者完成了12剂治疗；98例（67%）患者因神经病变提前停用奥沙利铂（中位=10剂，范围=4-12剂）。进一步的给药特征总结于表S3，中位随访时间为35.1个月，中位RFS为26个月（95%置信区间[CI]=19至39），总生存期未达到中位值。对于年龄超过70岁的队列，中位RFS为23个月（95%CI=14至未达到），中位总生存期为51个月（95%CI=37至未达到）。切除后8周内尽早开始改良FOLFIRINOX方案与改善的RFS（风险比=0.62，95%CI=0.41至0.96；P=0.033）和总生存期（风险比=0.53，95%CI=0.3至0.94；P=0.030）相关。KRAS变异和全基因组加倍倾向于缩短RFS和总生存期。同源重组缺陷状态并未带来更好的生存结果。
在非试验环境中，辅助性改良FOLFIRINOX方案对接受过PDAC切除术的患者有效且耐受性良好，包括年龄超过70岁的患者。
