Neoadjuvant therapy in pancreatic adenocarcinoma: A meta-analysis of phase II trials

Abstract

Background Neoadjuvant treatment has proven beneficial for many GI malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. This meta-analysis examines the best available phase II trials using neoadjuvant treatment for resectable and borderline/unresectable pancreatic adenocarcinoma. Methods Phase II trials were identified using a MEDLINE search, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. Patients were divided into two groups: patients with initially resectable tumors (Group A), and patients with borderline/unresectable tumors (Group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results A total of 14 phase II clinical trials including 536 patients were analyzed. Following treatment, resectability was 65.8% (95% CI 55.4%–75.6%) compared with 31.6% in Group B (95% CI 14.0%–52.5%). A significant partial response was observed in patients with borderline/unresectable tumors; 31.8 (95% CI 24.2%–39.8%) in Group B, and 9.5% (95% CI 2.9%–19.4%) in Group A (p=0.003). Progressive disease was seen in 17.0% (95% CI 11.9%–22.7) of patients in Group A versus 21.8% (95% CI 10.1%–36.5%) in Group B (p=0.006). Median survival in resected patients was 23 months for Group A, and 22.3 months for Group B. Conclusion Neoadjuvant treatment appears to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one-third of tumors initially deemed marginal for operative intervention were ultimately able to be resected following treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.

FOLFIRINOX-Based Neoadjuvant Therapy in Borderline Resectable or Unresectable Pancreatic Cancer

“…7 The median OS in our studies was systematically absent because it was not reached at the time of the final analysis. Our RR was similar to that of the registrative trial (35%), and this value is similar to the overall RR calculated in the meta-analyses of Gillen et al 3 and Assifi et al 4 However, in nonmetastatic disease, estimation of size reduction of the primary tumor is difficult in a primary PC tumor. It is likely that the pathologic (partial and complete) response is more clinically meaningful in this case.…”

“…3,4 Whether resection of locally advanced PC confers a survival, benefit is still unknown, because only a few, small, randomized trials have been published to date, and the quality of the evidence is fairly poor. A Cochrane metaanalysis, however, calculated an increased chance of survival at 3 and 5 years for patients who underwent surgery compared with nonoperated subjects.…”

“…3,4 The main regimens used in the studies included in these systematic reviews are gemcitabine (GEM) and 5-fluorouracil (5FU) or GEM-based doublets followed by CT-RT with 5FU or GEM as a radiosensitizer. However, no randomized trials have prospectively validated this strategy in borderline resectable PC.…”

Pancreatic cancer: from state-of-the-art treatments to promising novel therapies

“…33 Nevertheless, several metaanalyses that included patients treated in the neoadjuvant setting have not consistently demonstrated improved survival with this approach compared to the outcomes expected with surgery and adjuvant chemotherapy. [34][35][36] Of note, a lack of consensus across institutions regarding which tumours are considered borderline resectable might have influenced the results of the meta-analyses. Moreover, a patient selection bias is inherent to adjuvant trials, as patients harbouring tumours with a high-risk biology often experience rapid disease progression and clinical deterioration after resection, and are unlikely to be eligible for enrolment.…”

Stent placement as a bridge to surgery in malignant biliary obstruction (pancreatic cancer, distal bile duct cancer, and hilar tumors)

“…Several meta-analyses show that up to onethird of unresectable locally advanced tumors can be ultimately resected after neoadjuvant treatment with comparable outcomes as patients with initially resectable tumors. 54,55 Surgery can be delayed for several months when receiving preoperative chemoradiation and in most instances, the administration of chemotherapy requires normalization of liver function. Therefore, PBD is required in these patients prior to neoadjuvant treatment.…”