Metastatic pancreatic adenocarcinoma (mPAC) is a fatal disease. Palliative chemotherapy has been the only treatment option for patients; a modest benefit on overall survival (OS) has been well established with single-agent gemcitabine or 5-FU since the 1990s. Nearly two decades later, in 2011, Conroy et al showed the superiority of the FOLFIRINOX regimen over gemcitabine alone (median OS, 11.1 vs 6.8 months; p<0.001). In 2013, Von Hoff et al demonstrated the OS benefit of gemcitabine+nab-paclitaxel (Gem-Nab) over gemcitabine alone (8.5 vs 6.7 months; HR 0.72; 95% CI 0.62 to 0.83; p<0.001). Currently, both regimens have been used in high-income countries, but nab-paclitaxel is less widely available in low- and middle-income countries.
Despite several efforts, no targeted therapy has shown improvement in OS in phase III trials, with the exception of a minimal benefit from adding erlotinib to gemcitabine. Recent data with PARP inhibitors in pancreatic tumours with BRCA or PALB mutations have shown promising results but only as maintenance therapy after palliative chemotherapy. In addition, even if such improvements are confirmed in phase III trials, only a minority of patients with pancreatic cancer harbour these mutations. Unfortunately, very few patients with pancreatic cancer benefit from current tumour-agnostic approaches, such as immunotherapy or NTRK inhibitors for those who harbour a microsatellite instability-high tumour or NTRK fusion, respectively.
Because of its poor prognosis and high incidence, there is substantial interest in developing better therapies to treat mPAC. Currently, there are 326 clinical trials registered at ClinicalTrials.gov investigating therapeutic regimens in mPAC. Among those, 36 are in the context of first-line therapy, and of those, only seven are investigating FOLFIRINOX, while 29 are investigating Gem-Nab as the backbone therapy. Notably, among the seven trials using FOLFIRINOX, only one is active, while two were withdrawn and none were recruiting or completed. Moreover, nearly all new therapies have been tested in combination with the Gem-Nab regimen.
Source: ESMO Open