From First Line to Sequential Treatment in the Management of Metastatic Pancreatic Cancer

Abstract

The current management of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is based on systemic chemotherapy. The results of the MPACT and PRODIGE clinical trials have demonstrated that the combination of nab-paclitaxel and gemcitabine (GEM) as well as FOLFIRINOX regimen result in improvement in overall survival when compared to GEM alone. Treatment guidelines now recommend either one of these two regimens as first line treatment for fit patients with mPDAC. Because no head-to-head comparison between the two regimens exists, the selection of one versus the other is based on clinical criteria. The design and eligibility criteria of these two clinical trials are dissimilar, making the results of the MPACT trial more applicable to the general population of patients with mPDAC. In addition, the combination of nab-paclitaxel and GEM is better tolerated and easier to administer in clinical practice than FOLFIRINOX. Furthermore, when the regimens are studied in comparable patient populations the efficacy results are very similar. Nanoliposomal irinotecan plus 5FU has recently demonstrated a significant increase in efficacy rates after a GEM-based treatment. Importantly, treatment of mPDAC should now be considered as a continuum care for patients who are fit, with second and even third line treatments. Different sequential treatment algorithms are proposed based on available data. In retrospective studies, patients who were managed with GEM-based regimens followed by fluoropyrimidine-based regimens appear to have the most favorable outcome.

Long-lasting response to third-line chemotherapy in metastatic pancreatic cancer

“…Retrospective studies showed extended overall survival with a second line in patients previously treated with gemcitabine-based therapies with a median overall survival of 12 to 15 months. 6 But the good response to second line was apparently influenced by longer first-line progression-free survival in these reports. 9 …”

“…Treatment decisions and prognostic differ according to patient- and disease-related factors. Variables associated with better outcomes are: <65 years old, 3 excellent performance status, tumors in the head of the pancreas, 6 low level of serum Ca19.9. 8 Surgery to the primary tumor and surgery of the metastatic disease are also associated with better overall survival.…”

“… 4 , 5 Although the response to currently available chemotherapy (ChT) remains low, the proportion of patients candidates to receive second- and third-line regimens increased due to better results with these 2 ChT combinations. 6 …”

A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma—A Proof of Antigen Discovery Feasibility in Three Patients

“…However, multiagent adjuvant therapy (modified folforinox) has been demonstrated to be more effective than gemcitabine alone in the adjuvant setting, but its use is limited only to patients with excellent performance status (5). Recently it has suggested that gemcitabine plus capecitabine is a valid option for these patients since it has been shown that it is more efficient than gemcitabine alone (6).…”

Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer

“…Gemcitabine is the first-line drug for chemotherapy in pancreatic carcinoma. Although the application of gemcitabine has a certain effect in terms of clinical benefit, it has limited control of progression of pancreatic carcinoma[5,6]. However, chemoresistance is a tough barrier in the treatment of pancreatic carcinoma, and the prognostic study has confirmed that the clinical effectiveness of gemcitabine is below 20%[7,8].…”