Princess Alexandra Hospital, Brisbane, QLD, Australia.
The University of Queensland, Brisbane, QLD, Australia.
Ann Surg Oncol. 2020 Jul;27(7):2506-2515. doi: 10.1245/s10434-020-08205-2. Epub 2020 Jan 29.
While combination therapy with nab-paclitaxel/gemcitabine (nab-gem) is effective in pancreatic ductal adenocarcinoma (PDAC), its efficacy as perioperative chemotherapy is unknown. The primary objective of this multicenter, prospective, single-arm, phase II study was to determine whether neoadjuvant therapy with nab-gem was associated with higher complete resection rates (R0) in resectable PDAC, while the secondary objectives were to determine the utility of radiological assessment of response to preoperative chemotherapy and the safety and efficacy of nab-gem as perioperative therapy.
Patients were recruited from eight Australian sites, and 42 patients with radiologically defined resectable PDAC and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Participants received two cycles of preoperative nab-paclitaxel 125 mg/m and gemcitabine 1000 mg/m on days 1, 8, and 15 (28-day cycle) presurgery, and four cycles postoperatively. Early response to chemotherapy was measured with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans on day 15.
Preoperative nab-gem was completed by 93% of participants, but only 63% postoperatively. Thirty-six patients had surgery: 6 (17%) were unresectable, 15 (52%) had R0 (≥ 1 mm) resections, 14 (48%) had R1 (< 1 mm) resections, and 1 patient did not have PDAC. Median progression-free survival was 12.3 months and median overall survival (OS) was 23.5 months: R0 patients had an OS of 35 months versus 25.6 months for R1 patients after surgery. Seven patients had not progressed after 43 months.
The GAP trial demonstrated that perioperative nab-gem was tolerable. Although the primary endpoint of an 85% R0 rate was not met, the R0 rate was similar to trials using a > 1 mm R0 resection definition, and survival rates were comparable with recent adjuvant studies.
纳武利尤单抗联合吉西他滨/白蛋白紫杉醇（nab-gem）在胰腺导管腺癌（PDAC）中具有疗效，但作为围手术期化疗的疗效尚不清楚。本多中心、前瞻性、单臂、Ⅱ期研究的主要目的是确定新辅助nab-gem 治疗是否与可切除 PDAC 中的更高完全切除率（R0）相关，次要目的是确定术前化疗反应的影像学评估的效用以及 nab-gem 作为围手术期治疗的安全性和有效性。
从 8 个澳大利亚站点招募患者，共纳入 42 例影像学定义的可切除 PDAC 患者，ECOG 体能状态为 0-2。患者接受术前nab-紫杉醇 125mg/m 和吉西他滨 1000mg/m，第 1、8 和 15 天（28 天周期），共 2 个周期，然后在术后接受 4 个周期。化疗的早期反应通过氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（FDG-PET/CT）在第 15 天测量。
93%的患者完成了术前 nab-gem 治疗，但只有 63%的患者完成了术后治疗。36 例患者接受了手术：6 例（17%）为不可切除，15 例（52%）为 R0（≥1mm）切除，14 例（48%）为 R1（<1mm）切除，1 例患者未患有 PDAC。中位无进展生存期为 12.3 个月，中位总生存期（OS）为 23.5 个月：R0 患者的 OS 为 35 个月，而 R1 患者术后的 OS 为 25.6 个月。7 例患者在 43 个月后仍未进展。
GAP 试验表明围手术期 nab-gem 是可以耐受的。尽管未达到 85%的 R0 率的主要终点，但 R0 率与使用>1mmR0 切除定义的试验相似，且生存率与最近的辅助研究相当。
