# Efficacy and Safety of Combination Therapy With Immune Checkpoint Inhibitors and Chemotherapy With Gemcitabine and Nab‐Paclitaxel in Pancreatic Cancer: A Systematic Review

## TL;DR

This review examines whether combining chemotherapy with immune checkpoint inhibitors improves outcomes in pancreatic cancer patients.

## Contribution

The study systematically evaluates the safety and potential efficacy of combining specific chemotherapy drugs with immune checkpoint inhibitors in pancreatic cancer.

## Key findings

- Combination therapy showed improved median overall survival (~15 months) compared to chemotherapy alone (8–9 months).
- Objective response rates ranged from 18% to 50% with combination therapy.
- Grade 3–4 adverse events were primarily hematologic and neurologic.

## Abstract

Pancreatic cancer (PC) is a lethal malignancy with a 5‐year survival rate of 13% as the 7th leading cause of cancer‐related death worldwide. Most patients are ineligible for resection at diagnosis. Monotherapy with immune checkpoint inhibitors (ICIs) has shown limited success in PC, with objective response rates below 5% and median overall survival rarely exceeding 6 months. This systematic review evaluates the efficacy and safety of combining gemcitabine and nab‐paclitaxel with ICIs in pancreatic cancer.

To assess the efficacy and safety of combining gemcitabine and nab‐paclitaxel chemotherapy with ICIs in patients with pancreatic cancer.

A comprehensive search of PubMed, Scopus, and Web of Science was performed using predefined keywords. Eligible studies included original research articles employing interventional, cohort, case–control, or cross‐sectional designs. Case reports, case series, and review articles were excluded. Data extraction and quality assessment using the Mixed Methods Appraisal Tool (MMAT, 2018) were conducted independently by two reviewers.

Of 1904 search results, seven studies met inclusion criteria: four clinical trials and three retrospective cohorts. Sample sizes ranged from 17 to 180 participants with advanced or locally advanced PC. Median overall survival was ~15 months (range: 9.8–16.7) versus 8–9 months for chemotherapy alone. Progression‐free survival ranged from 5.5–9 versus 3.5–5.5 months. Objective response rates varied between 18%–50% for combination therapy and 23%–29% for chemotherapy. Grade 3–4 adverse events were mainly hematologic (anemia, neutropenia) and neurologic (fatigue, peripheral neuropathy). ICIs included PD‐1 inhibitors (pembrolizumab, nivolumab, toripalimab, camrelizumab, tislelizumab, sintilimab), PD‐L1 inhibitor (durvalumab), and CTLA‐4 inhibitor (tremelimumab).

Combining ICIs with gemcitabine and nab‐paclitaxel appears feasible and safe, with signals of improved efficacy compared with chemotherapy alone. However, evidence remains limited, and further large‐scale trials are warranted to confirm survival benefits and optimize therapeutic strategies in pancreatic cancer.