99P - Efficacy and safety of toripalimab plus metronomic chemotherapy in HER2 negative metastatic breast cancer

Background

Combining immune checkpoint blockade (ICB) with chemotherapy may significantly improve efficacy in patients with breast cancer. Whether metronomic chemotherapy is more suitable for ICB than conventional chemotherapy is still unclear.

Methods

This study is a multicenter randomized phase 2 trial using a multi-arm design with Bayesian adaptive randomization and efficacy monitoring. Eligible patients have advanced HER2-negative breast cancer, with no more than one prior line of standard chemotherapy. Patients were randomized to 5 groups: 1) metronomic vinorelbine (NVB, 40 mg/day, TIW) monotherapy (the control cohort); 2) NVB + toripalimab (anti-PD1 antibody, 240 mg Q3W); 3) bevacizumab (5 mg/kg Q3W) + NVB+ toripalimab (the BEV cohort); 4) cisplatin (50mg/m Q3W) + NVB + toripalimab (the DDP cohort); 5) cyclophosphamide (50mg/day, QD) + capecitabine (500 mg, TID) + NVB+ toripalimab (the VEX cohort). The primary endpoint was disease control rate (DCR). Mass cytometry time-of-flight analyses of paired blood samples were performed to demonstrate dynamic changes in systemic immune profile.

Results

A total of 103 patients were randomized. The rate of nausea was significantly higher in the cisplatin cohort than in the others (P< 0.001). Among the five treatment cohorts, the VEX cohort and the cisplatin cohort had the highest DCR, 69.7% (95% CI 51.7–85.9%) and 73.7% (95% CI 56.1–88.7%), respectively. It is worth noting that the PFS of patients in the VEX cohort was the longest, reaching 6.6 months (95% CI 4.0-5.9). The PFS of patients in the DDP cohort was relatively short, only 3.5 months (95% CI 2.2-5.3). In the TNBC subgroup, again, patients in the VEX cohort had the highest DCR (74.1%, 95%CI 47.9%-95.4%) and longest PFS (9.8 months, 95%CI 3.8-21.9). We clustered CD45+ immune cells into 32 clusters. Only the change of cluster 30 differed between responders and non-responders. This is a group of intermediate monocytes with a high expression of CD38. Meanwhile, the overall expression of CD38 in monocytes was significantly increased by DDP and BEV treatment compared with baseline, but not in the VEX groups.

Conclusions

These data suggest promising clinical efficacy and evidence of cooperativity between metronomic VEX chemotherapy and PD-1 blockade.

Clinical trial identification

NCT04389073.

Legal entity responsible for the study

The authors.

Funding

CAMS Innovation Fund for Medical Sciences (CIFMS 2022-I2M-C&T-B-067).

Disclosure

All authors have declared no conflicts of interest.