Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
J Clin Oncol. 2023 Dec 1;41(34):5263-5273. doi: 10.1200/JCO.23.00506. Epub 2023 Aug 3.
To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with / wild-type metastatic colorectal cancer (mCRC).
PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable / wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time 6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).
Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively ( < .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.
Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with / wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.
验证改良氟尿嘧啶、亚叶酸钙和奥沙利铂（mFOLFOX）双联化疗与氟尿嘧啶加亚叶酸钙（5-FU+LV）单药化疗联合帕尼单抗（PAN）作为初治老年野生型转移性结直肠癌（mCRC）患者的初始治疗方案是否均能取得满意疗效。
PANDA（临床试验.gov 标识符：NCT02904031）是一项开放标签、随机、Ⅱ期非对照临床试验，纳入了未经治疗的年龄≥70 岁且不可切除/野生型 mCRC 患者。患者按 1:1 随机分配至 mFOLFOX+PAN（A 组）或 5-FU+LV+PAN（B 组），最多接受 12 个周期的治疗，然后接受 PAN 维持治疗。主要终点为无进展生存期（PFS）。在每个组中，假设中位 PFS 时间为 6 个月且目标 PFS≥9.65，每组需要 90 例患者才能达到 90%的效能和 5%的Ⅰ类错误（单侧 Brookmeyer-Crowley 检验）。
2016 年 7 月至 2019 年 4 月，91 例患者被随机分配至 A 组，92 例患者被分配至 B 组。中位随访时间为 50.0 个月（IQR，45.6-56.4）时，A 组和 B 组的中位 PFS 分别为 9.6 和 9.0 个月（两组均<0.001）。总体缓解率分别为 69%和 52%，而 A 组和 B 组的中位总生存期分别为 23.5 和 22.0 个月。≥2 级化疗相关不良事件的总体发生率分别为 60%和 37%。基线 G8 和高年龄患者化疗风险评估量表评分具有预后意义，但与两组的疗效和安全性无关。
mFOLFOX 和 5-FU+LV+PAN 均是初治老年野生型 mCRC 患者的合理治疗选择，5-FU+LV+PAN 具有更好的安全性。
