PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer.

patients_and_methods

Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in BRCA1/2 or PALB2.

患者按1:1的比例随机分配到mFFX或GnP组，排除了BRCA1/2或PALB2基因的胚系致病性变异。

The primary end point was progression-free survival(PFS) between arms with 0.3 significance.

主要终点是两组之间的无进展生存（PFS），显著性水平为0.3。

The per-protocol (PP) population included patients who received one dose of chemotherapy.

按方案（PP）人群包括接受了至少一剂化疗的患者。

Pretreatment biopsies underwent whole-genome/transcriptome sequencing and patient-derived organoid (PDO) development, providing correlate recommendations at a molecular tumor board and outcomes assessed according to RNA signatures (basal-like v classical).

治疗前活检样本进行了全基因组/转录组测序和患者来源的类器官（PDO）开发，为分子肿瘤委员会提供了相关建议，并根据RNA特征（基底样与经典型）评估了结果。

Results

Of 160 patients randomly assigned (80 mFFX, 80 GnP), 140 patients were in the PP population (71 mFFX, 69 GnP), with median follow-up of 8.3 months.

在随机分配的160名患者中（80名mFFX，80名GnP），有140名患者进入了PP人群（71名mFFX，69名GnP），中位随访时间为8.3个月。

The median PFS was 4.0 months for mFFX versus 5.3 months for GnP (hazard ratio[HR], 1.37 [95% CI, 0.97 to 1.92]; P = .069) in intention-to-treat.

意向治疗人群中，mFFX的中位无进展生存期为4.0个月，而GnP为5.3个月（风险比[HR]，1.37 [95% 置信区间，0.97至1.92]；P = .069）。

Median overall survival(OS) was 8.5 months with mFFX and 9.7 months with GnP (HR, 1.57 [95% CI, 1.08 to 2.28]; P = .017).

意向治疗人群中，mFFX的中位总生存期为8.5个月，而GnP为9.7个月（风险比[HR]，1.57 [95% 置信区间，1.08至2.28]；P = .017）。

Genomic data were generated in 94%, transcriptomes in 74%, and PDOs in 50%.

94%的样本生成了基因组数据，74%的样本生成了转录组数据，50%的样本生成了患者来源的异种移植（PDO）数据。

The median PFS for those with basal-like was 3.0 (mFFX) and 5.5 (GnP) months (P = .17), and classical PDAC was 6.3 (mFFX) versus 5.4 (GnP) months (P = .36).

具有基底样特征的患者的中位无进展生存期（PFS）为3.0个月（mFFX治疗组）和5.5个月（GnP治疗组）（P = .17），而经典型胰腺导管腺癌患者的中位PFS为6.3个月（mFFX治疗组）对比5.4个月（GnP治疗组）（P = .36）。

The median OS in basal-like was 7.5 (mFFX) and 8.9 (GnP) months (P = .75) versus in classical OS was 9.7 (mFFX) and 13.9 (GnP) months (P = .047).

在基底样亚型中，总生存期的中位数为7.5个月（mFFX方案）和8.9个月（GnP方案）（P = .75），而在经典亚型中，总生存期的中位数为9.7个月（mFFX方案）和13.9个月（GnP方案）（P = .047）。

Overall, 75 (54%) of patients received second-line treatment, 33/75 (44%) correlate-guided.

总体而言，75名（54%）患者接受了二线治疗，其中33/75名（44%）是根据相关指导进行的。

The median time on second-line treatment was only 2.1 months with a median OS of 5.4 months for a correlate-guided choice versus 4.4 months on a standard chemotherapy approach (P = .45).

在二线治疗中，相关指导选择的中位治疗时间为2.1个月，总生存期为5.4个月，而标准化疗方法的总生存期为4.4个月（P = .45）。

Conclusions

In the phase II Pancreatic Adenocarcinoma Signature Stratification for Treatment-01 (PASS-01) trial population, PFS was similar between GnP and mFFX; however, OS and safety trends favored GnP.

在二期胰腺导管腺癌特征分层治疗-01（PASS-01）试验人群中，GnP和mFFX的无进展生存期（PFS）相似；然而，总生存期（OS）和安全性趋势更倾向于GnP。

The second-line setting appears inadequate to offer precision choices, given the short survival observed.

鉴于观察到的生存期较短，二线治疗似乎不足以提供精确的选择。