# PD‐1/PD‐L1 Inhibitors Plus Chemotherapy Versus Chemotherapy Alone as First‐Line Therapy for Patients With Unfavorable Cancer of Unknown Primary: A Multicenter, Retrospective Cohort Study

## TL;DR

Adding PD-1/PD-L1 inhibitors to chemotherapy improves survival and response rates in patients with hard-to-treat cancer of unknown primary.

## Contribution

This study shows that combining PD-1/PD-L1 inhibitors with chemotherapy is more effective than chemotherapy alone for first-line treatment of unfavorable CUP.

## Key findings

- Patients receiving PD-1/PD-L1 inhibitors plus chemotherapy had significantly longer progression-free and overall survival.
- The combination therapy had a higher objective response rate and fewer severe side effects compared to chemotherapy alone.
- Benefits were observed even in patients receiving taxane plus platinum-based chemotherapy.

## Abstract

This multicenter study aimed to investigate the efficacy and safety of PD‐1/PD‐L1 inhibitors plus chemotherapy (ICI‐Chemo group) versus chemotherapy alone (Chemo group) for patients with cancer of unknown primary (CUP) in the first‐line setting. We included patients with unfavorable CUP across four medical centers in China. Between January 2014 and December 2023, 117 patients were enrolled: 46 patients in the ICI‐Chemo group and 71 patients in the Chemo group. After a median follow‐up of 28.1 months, the ICI‐Chemo group exhibited a significant improvement over the Chemo group in median PFS (9.10 months vs. 6.37 months; hazard ratio [HR] 0.46; 95% CI: 0.30–0.71; p < 0.001) and OS (35.67 months vs. 10.2 months; HR 0.37; 95% CI: 0.22–0.64; p < 0.001). Similarly, among patients who received TP (taxane plus platinum)‐based chemotherapies, OS and PFS benefits were observed in the ICI‐Chemo group. The objective response rate was higher in the ICI‐Chemo group than in the Chemo group (54.35% vs. 22.53%, p < 0.001). Grade 3 or higher drug‐related adverse events occurred in 11 patients (23.91%) in the ICI‐Chemo group and 28 patients (39.44%) in the Chemo group. Thus, PD‐1/PD‐L1 inhibitors plus chemotherapy could be the preferred first‐line treatment for patients with unfavorable CUP, providing improved efficacy and manageable toxicity.

We assessed the efficacy and safety of PD‐1/PD‐L1 inhibitors plus chemotherapy versus chemotherapy alone for patients with cancer of unknown primary (CUP) in the first‐line setting. In this cohort study of 117 patients, PD‐1/PD‐L1 inhibitors plus chemotherapy delivered progression‐free survival and overall survival advantages, along with a higher objective response rate, when compared to chemotherapy. The findings indicated that PD‐1/PD‐L1 inhibitors plus chemotherapy could be the preferred first‐line approach for patients with unfavorable CUP.