# Characteristics of patients with metastatic renal cell carcinoma who do not respond to axitinib treatment

**Authors:** Kojiro Ohba, Takahiro Osawa, Takahiro Kojima, Tomohiko Hara, Mikio Sugimoto, Masatoshi Eto, Keita Minami, Yasutomo Nakai, Kosuke Ueda, Sei Naito, Norio Nonomura, Sachiyo Murai, Hiroyuki Nishiyama, Hiromi Nakanishi, Yuta Mukae, Kensuke Mitsunari, Tomohiro Matsuo, Ryoichi Imamura, Nobuo Shinohara

PMC · DOI: 10.1007/s10147-025-02715-3 · International Journal of Clinical Oncology · 2025-02-14

## TL;DR

This study identifies factors that predict poor response to axitinib in kidney cancer patients and suggests better treatment options for those who don't respond well.

## Contribution

The study identifies independent risk factors for early disease progression on axitinib and compares the effectiveness of next-line treatments.

## Key findings

- Early disease progression was more common in patients without nephrectomy, short prior TKI treatment, and IMDC poor risk category.
- TKIs provided better progression-free survival than nivolumab or mammalian target of rapamycin inhibitors in patients with early disease progression.
- Nephrectomy status, prior TKI duration, and IMDC risk category are independent risk factors for early disease progression on axitinib.

## Abstract

Axitinib is a widely used tyrosine kinase inhibitor (TKI) in metastatic renal cell carcinoma (mRCC) treatment. Here, we analyzed the characteristics of patients who did not respond to axitinib and evaluated alternative options for their treatment.

We retrospectively analyzed data for 449 patients with mRCC who were administered axitinib following another TKI as initial therapy. Patients with progressive disease (PD) at their first assessment were defined as showing early-PD. We analyzed the characteristics of patients at risk of early-PD and evaluated the relationship between the treatment following axitinib and their prognosis.

Early-PD was diagnosed in 102 patients, and was more common in those who had not undergone nephrectomy (p < 0.001), those treated with a TKI for a short period (p < 0.001), and those in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) poor risk category for mRCC (p < 0.001). Multivariate analysis showed that these were independent risk factors for early-PD (all p < 0.001). Of those with early-PD, 52 changed to next-line treatment. The progression-free survival periods were 5.5 (95% confidence interval (CI) 2.4–8.6) months for patients administered TKIs, 4.2 (95% CI 0.3–8.1) months for those on nivolumab, and 2.2 (1.8–2.6) months for those on mammalian target of rapamycin inhibitors (p = 0.030).

Patients who have not undergone nephrectomy, those previously treated with another TKI for a short period, and those in the IMDC poor risk category are more likely to experience early-PD when taking axitinib. Furthermore, TKIs are the best treatment for patients with early-PD who have previously been administered axitinib.

## Linked entities

- **Chemicals:** axitinib (PubChem CID 3086685)

## Full-text entities

- **Genes:** TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}
- **Diseases:** Metastatic Renal Cell Carcinoma (MESH:C538445), PD (MESH:D018450)
- **Chemicals:** Axitinib (MESH:D000077784), 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/PMC11947068