A mixed inflammatory peripheral signature defines clinical outcomes in a phase II trial combining pembrolizumab with paclitaxel and carboplatin in melanoma.
Caroline Lambert, Rahima Jamal, Paméla Thébault et al.
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In 30 seconds
This multicenter phase II trial evaluated pembrolizumab plus carboplatin/paclitaxel (CP) in 30 patients with unresectable or metastatic melanoma who had not received prior immunotherapy. The overall response rate by immune-related response criteria was 43%, disease control rate was 53%, and median overall survival was 23.8 months. Grade 3 or higher adverse events occurred in 50% of patients. The investigators reported no apparent response or survival advantage from adding CP compared with immunotherapy alone, while the combination was less tolerable. Peripheral immune features associated with response or survival were identified for further study.
Key findings
- The overall response rate was 43% and the disease control rate was 53% by irRC criteria.
- Median overall survival was 23.8 months; grade 3 and higher adverse events occurred in 50% of patients.
- Response was associated with baseline peripheral immune features, including lower naive CD8 T-cell frequency and low plasma CCL3.
- Pro-inflammatory soluble factors increased after treatment in both responders and non-responders.
Why it matters
The findings illustrate the trade-off observed with this chemotherapy–checkpoint inhibitor combination: clinically meaningful responses occurred, but severe adverse events were common and the study did not suggest added response or survival benefit over immunotherapy alone. The peripheral immune associations may help guide biomarker research, but they are exploratory and do not establish markers for selecting treatment.
What to keep in mind
The study was a phase II trial with 30 patients, and the reported peripheral immune associations are correlational; the abstract does not describe a randomized comparison with immunotherapy alone.