Pathological complete response following neoadjuvant chemotherapy with PD-1 inhibitor for locally advanced pancreatic...

In recent years, the incidence of pancreatic cancer has shown an obvious increasing trend worldwide and even causes a greater disease burden to the mankind. Due to the lack of effective early surveillance methods, patients are often in the middle to advanced stages of their disease at the time of detection, thus losing the opportunity for surgery. The currently available chemotherapy regimens are yet to be further improved to prolong patient survival. The use of immune monotherapy in pancreatic cancer is even more frustrating, with poor therapeutic results.

Here, we present two cases of locally advanced pancreatic cancer in which neoadjuvant chemotherapy (gemcitabine with albumin-bound paclitaxel) was administered in combination with a programmed cell death protein 1 (PD-1) inhibitor (tislelizumab), resulting in the opportunity for surgical intervention. Notably, one patient exhibited a pathological complete response, characterized by minimal residual highly intraepithelial neoplasia accompanied by extensive fibrosis and transparency. Genetic testing found that the patient had a KRAS mutation (c.35G>T, p.G12V).

The efficacy of this combination therapy has renewed our interest in the mechanism of action or drug resistance of tumor cells in chemotherapy and immunotherapy. An in-depth study of the possible synergistic mechanisms of action of these drugs will provide new research directions for the treatment of pancreatic cancer.