# Good response with nivolumab and cabozantinib combination therapy in patients with metastatic collecting duct carcinoma with high expression of PD-L1, c-MET, and AXL

**Authors:** Tatsuya Umemoto, Masanori Hasegawa, Jun Naruse, Tatsuo Kano, Nobuyuki Nakajima, Masahiro Nitta, Yoshiaki Kawamura, Hiroshi Kajiwara, Sunao Shoji

PMC · DOI: 10.1007/s13730-025-01027-9 · CEN Case Reports · 2025-09-08

## TL;DR

Combining nivolumab and cabozantinib showed promising results in treating metastatic kidney cancer with specific protein markers.

## Contribution

First report of successful combination therapy for metastatic collecting duct carcinoma with high PD-L1, c-MET, and AXL expression.

## Key findings

- Two patients with metastatic CDC showed significant response to nivolumab and cabozantinib therapy.
- High PD-L1, c-MET, and AXL expression was associated with favorable treatment outcomes.
- Laparoscopic nephrectomy followed successful therapy in both cases.

## Abstract

Collecting duct carcinoma (CDC) is a rare subtype of renal cell carcinoma with a poor prognosis. Moreover, despite various chemotherapeutic strategies and administration of several tyrosine kinase inhibitors for metastatic CDC, the outcomes remain unfavorable, with no established treatment. Herein, we report the cases of two patients with CDC who exhibited a good response to nivolumab and cabozantinib combination therapy. Both patients were diagnosed with CDC via a needle biopsy of the renal tumor, revealing high expression levels of programmed death ligand 1 (PD-L1), c-MET, and AXL. After 10 and 12 courses of combination therapy for Cases 1 and 2, respectively, significant response was observed against the primary and metastatic lesions. Subsequently, the patients underwent laparoscopic nephrectomy. To the best of our knowledge, this is the first report documenting the favorable therapeutic response of nivolumab and cabozantinib combination therapy against metastatic CDC in patients with high expression of the corresponding molecular targets. These findings may have a strong implication in the selection of first-line systemic therapies for metastatic CDC.

## Linked entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126], MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233], AXL (AXL receptor tyrosine kinase) [NCBI Gene 558]
- **Chemicals:** cabozantinib (PubChem CID 25102847)
- **Diseases:** collecting duct carcinoma (MONDO:0005220), renal cell carcinoma (MONDO:0005086)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, AXL (AXL receptor tyrosine kinase) [NCBI Gene 558] {aka ARK, AXL3, JTK11, Tyro7, UFO}, MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233] {aka AUTS9, DA11, DFNB97, HGFR, RCCP2, c-Met}
- **Diseases:** CDC (MESH:D002292), renal tumor (MESH:D007680)
- **Chemicals:** cabozantinib (MESH:C558660), nivolumab (MESH:D000077594)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12605844