Objective

The objective of this study was to evaluate whether building upon multidrug chemotherapy regimens represents a viable strategy in pancreatic cancer clinical trial design.

Methods

We performed a pooled analysis of all single-arm phase II studies in which a specific targeted agent (the anti-vascular endothelial growth factor monoclonal antibody bevacizumab) was added to gemcitabine-based cytotoxic doublets. The primary end point was overall survival (OS). Secondary end points included objective response rate, CA-19-9 biomarker response rate, and adverse event frequencies. Kaplan-Meier methods estimated time-to-event end points, whereas the Cox proportional hazard model estimated univariate hazard ratios of death.

Results

For the 300 patients included in the pooled analysis, median OS was 9.1 months (95% confidence interval, 8.3-10.2). Differences in OS were observed according to patients' baseline performance status (median OS, 10.4 vs 8.6 months for Eastern Cooperative Oncology Group 0 vs 1, respectively). Moreover, bevacizumab-related adverse events were not observed at increased frequency with gemcitabine-based doublets compared with historic data.

Conclusions

Recognizing the limitations of cross-study comparisons, these results compare favorably to those from Cancer and Leukemia Group B 80303, a phase III trial testing bevacizumab in combination with gemcitabine alone. This is the largest data set available to demonstrate the feasibility of building upon more intensive chemotherapy backbones in clinical trials of novel targeted agents in pancreatic cancer.

Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival <12 months. Therefore, novel treatment options are needed. Currently, there is no brachytherapy device approved for pancreatic cancer treatment. Hereby, we present the protocol of a prospective, multicenter, interventional, open-label, single-arm pilot study (OncoPac-1, Clinicaltrial.gov-NCT03076216) aiming to determine the safety and efficacy of Phosphorus-32 when implanted directly into pancreatic tumors using EUS guidance, for patients with unresectable LAPC undergoing chemotherapy (gemcitabine ± nab-paclitaxel).