Anthem Innovation Israel, Ltd, Tel Aviv, Israel.
Division of Hematology and Oncology, Department of Medicine and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
JAMA Netw Open. 2022 Jun 1;5(6):e2216199. doi: 10.1001/jamanetworkopen.2022.16199.
FOLFIRINOX (leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) and gemcitabine plus nab-paclitaxel are the 2 common first-line therapies for metastatic adenocarcinoma of the pancreas (mPC), but they have not been directly compared in a clinical trial, and comparative clinical data analyses on their effectiveness are limited.
To compare the FOLFIRINOX and gemcitabine plus nab-paclitaxel treatments of mPC in clinical data and evaluate whether there are differences in overall survival and posttreatment complications between them.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective, nonrandomized comparative effectiveness study used data from the AIM Specialty Health-Anthem Cancer Care Quality Program and from administrative claims of commercially insured patients, spanning 388 outpatient centers and clinics for medical oncology located in 44 states across the US. Effectiveness and safety of the treatments were analyzed by matching or adjusting for age, Charlson Comorbidity Index, ECOG performance status (PS) score, Social Deprivation Index (SDI), liver and lymph node metastasis, prior radiotherapy or surgical procedures, and year of treatment. Patients with mPC treated between January 1, 2016, and December 31, 2019, and followed up until June 30, 2020, were included in the analysis.
Initiation of treatment with FOLFIRINOX or gemcitabine plus nab-paclitaxel.
Outcomes were overall survival and posttreatment costs and hospitalization. Median survival time was calculated using Kaplan-Meier estimates adjusted with inverse probability of treatment weighting and 1:1 matching.
Among the 1102 patients included in the analysis (618 men [56.1%]; median age, 60.0 [IQR, 55.5-63.7] years), those treated with FOLFIRINOX were younger (median age, 59.1 [IQR, 53.9-63.3] vs 61.2 [IQR, 57.2-64.3] years; P < .001), with better PS scores (226 [39.9%] with PS of 0 in the FOLFIRINOX group vs 176 [32.8%] in the gemcitabine plus nab-paclitaxel group; P = .02), fewer comorbidities (median Charlson Comorbidity Index, 0.0 [IQR, 0.0-1.0] vs 1.0 [IQR, 0.0-1.0]), and lower SDI (median, 36.0 [IQR, 16.2-61.0] vs 42.0 [IQR, 23.8-66.2]). After adjustments, the median overall survival was 9.27 (IQR, 8.74-9.76) and 6.87 (IQR, 6.41-7.66) months for patients treated with FOLFIRINOX and gemcitabine plus nab-paclitaxel, respectively (P < .001). This survival benefit was observed among all subgroups, including different ECOG PS scores, ages, SDIs, and metastatic sites. FOLFIRINOX-treated patients also had 17.3% fewer posttreatment hospitalizations (P = .03) and 20% lower posttreatment costs (P < .001).
In this comparative effectiveness cohort study, FOLFIRINOX was associated with improved survival of approximately 2 months compared with gemcitabine plus nab-paclitaxel and was also associated with fewer posttreatment complications. A randomized clinical trial comparing these first-line treatments is warranted to test the survival and posttreatment hospitalization (or complications) benefit of FOLFIRINOX compared with gemcitabine plus nab-paclitaxel.
FOLFIRINOX（亚叶酸钙[叶酸]、氟尿嘧啶、盐酸伊立替康和奥沙利铂）和吉西他滨加 nab-紫杉醇是转移性胰腺腺癌（mPC）的两种常见一线治疗方法，但它们尚未在临床试验中直接比较，并且对其疗效的比较临床数据分析有限。
比较 FOLFIRINOX 和吉西他滨加 nab-紫杉醇治疗 mPC 的临床数据，并评估它们在总生存期和治疗后并发症方面是否存在差异。
设计、设置和参与者：这是一项回顾性、非随机的比较有效性研究，使用了 AIM Specialty Health-Anthem Cancer Care Quality Program 和商业保险患者行政索赔的数据，涵盖了美国 44 个州的 388 个门诊中心和医学肿瘤学诊所。通过匹配或调整年龄、Charlson 合并症指数、ECOG 表现状态（PS）评分、社会剥夺指数（SDI）、肝和淋巴结转移、既往放疗或手术、以及治疗年份来分析治疗的有效性和安全性。纳入分析的患者为 2016 年 1 月 1 日至 2019 年 12 月 31 日期间接受治疗且随访至 2020 年 6 月 30 日的 mPC 患者。
开始接受 FOLFIRINOX 或吉西他滨加 nab-紫杉醇治疗。
结局为总生存期和治疗后费用及住院情况。使用 Kaplan-Meier 估计值和逆概率治疗加权及 1:1 匹配进行调整后计算中位生存时间。
在分析中纳入的 1102 例患者（618 例男性[56.1%]；中位年龄 60.0 [IQR，55.5-63.7] 岁）中，接受 FOLFIRINOX 治疗的患者更年轻（中位年龄 59.1 [IQR，53.9-63.3] 岁 vs 61.2 [IQR，57.2-64.3] 岁；P<0.001），PS 评分更好（FOLFIRINOX 组中有 226 例[39.9%] PS 为 0，而吉西他滨加 nab-紫杉醇组中有 176 例[32.8%]；P=0.02），合并症较少（中位 Charlson 合并症指数 0.0 [IQR，0.0-1.0] vs 1.0 [IQR，0.0-1.0]），SDI 较低（中位数 36.0 [IQR，16.2-61.0] vs 42.0 [IQR，23.8-66.2]）。调整后，接受 FOLFIRINOX 和吉西他滨加 nab-紫杉醇治疗的患者的中位总生存期分别为 9.27（IQR，8.74-9.76）和 6.87（IQR，6.41-7.66）个月（P<0.001）。在所有亚组中，包括不同的 ECOG PS 评分、年龄、SDI 和转移部位，均观察到这种生存获益。接受 FOLFIRINOX 治疗的患者治疗后住院率也降低了 17.3%（P=0.03），治疗后费用降低了 20%（P<0.001）。
在这项比较有效性队列研究中，与吉西他滨加 nab-紫杉醇相比，FOLFIRINOX 治疗可使生存时间延长约 2 个月，且与较少的治疗后并发症相关。需要进行随机临床试验来比较这两种一线治疗方法，以检验 FOLFIRINOX 与吉西他滨加 nab-紫杉醇相比在总生存期和治疗后住院（或并发症）获益方面的优势。
