Camrelizumab combined with apatinib and albumin-bound paclitaxel followed by camrelizumab plus apatinib as first-line therapy for unresectable or metastatic pancreatic cancer.

Abstract

703 Background: Pancreatic carcinoma has complex immunosuppressive tumor microenvironment that acts to insulate the tumor against an effective cytotoxic immune response. Apatinib (small molecular agent targeting the VEGFR-2), has shown the potential additive or synergistic antitumor effects with camrelizumab (anti-PD-1 agent) in vitro study. The inhibition of VEGF signaling pathway could trigger immune suppression provoked. Considering the anti-PD-1 agent plus antiangiogenic drug might avoid the substantial cumulative toxicities and obtain well tolerance, the specific and optimized therapeutic agents and treatment strategy to carry out chemotherapy-free strategy as maintenance or sequential (switch maintenance) therapy is hopeful and noteworthy. Methods: In this single-arm, single-center, exploratory study, patients (pts) who were pathologically or cytologically diagnosed as unresectable or metastatic pancreatic cancer and had not received systemic treatment before, with an ECOG performance status of 0-2. Pts received camrelizumab (200 mg intravenously once every 3 weeks) plus albumin-bound paclitaxel (125 mg/m2 intravenously on day 1,8 every 3 weeks) and apatinib (250 mg once daily orally on days 1–21 of each 3-week cycle) for 4–6 cycles, and pts without progressive disease (PD) after completing 4–6 cycles of initial camrelizumab plus albumin-bound paclitaxel and apatinib were administrated subsequent camrelizumab (200 mg intravenously once in 3 weeks) plus apatinib (250 mg once daily orally on days 1–21 of each 3-week cycle). Primary endpoint was progressionfree survival (PFS) by RECIST 1.1. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From 09/2021 to 08/2022 13 pts were enrolled (median age 60, 77% male). At data cutoff, 5 pts continued to receive subsequent camrelizumab plus apatinib, 12 pts were included in the efficacy analysis. The ORR was 16.7%, with confirmed 2 (16.7%) PR. SD were 9 (75.0%) with a DCR of 91.7%. All pts experienced treatment-related AEs (TRAEs), the ≥grade 3 TRAEs were GGT increased (31%), blood bilirubin increased (8%), alanine aminotransferase increased (8%), aspartate aminotransferase increased (8%), alkaline phosphatase increased (8%), creatinine increased (8%), hypoesthesia (8%) and malaise (8%). Of 13 patients, 5 (38%) had TRAEs leading to any treatment interruption, and 5 (38%) patients had TRAEs leading to any dose reduction, respectively. None patient died because of TRAEs. Conclusions: Camrelizumab combined with apatinib and albumin-bound paclitaxel followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as firstline therapy for patients with unresectable or metastatic pancreatic cancer. Clinical trial information: ChiCTR2100045844 .