Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib

The aim of this study is to describe the genomic profiling of patients with metastatic renal cell carcinoma (mRCC) who are long-lasting responders to treatment with cabozantinib and patients who are not long-lasting responders to the cabozantinib treatment.

The study plan to enroll about 80 patients in 10 Italian centers:

Group A: 40 patients defined as long-lasting responders (PFS ≥ 9 months) Group B: 40 patients defined as primary refractories to cabozantinib (PFS ≤ 3 months)

Tissue samples from nephrectomy or from a metastatic site will be used to perform genomic profiling not older than 5 years.Tissue should be formalin-fixed, paraffin-embedded (FFPE).

Genomic profiling will be performed with a hybrid capture-based next-generation sequencing assay (FoundationONE). The sample will be assayed for all coding exons of 324 cancer-related genes plus select introns from 34 genes that are frequently rearranged in cancer. Sequencing will be performed to a mean exon coverage depth of >500X. The resulting sequences will be analyzed for all classes of genomic alteration, including short variant alterations, copy number alterations, and selected gene fusions or rearrangements.

• Cabozantinib (Drug): Patients must have been treated with cabozantinib after one or more previous therapies for mRCC, as per clinical practise.

Primary outcomes

• Genomic profiling [12 months]: to describe genomic profiling of patients with mRCC who are long-lasting responders (PFS ≥9 months) to cabozantinib and describe genomic profiling of patients with rapid disease progression following cabozntinib therapy (PFS≤ 3 months)

Secondary outcomes

• Overall Survival (OS) [12 months]: to describe OS based according to detected genomic profiling
• Overall response rate (ORR) [12 months]: to describe ORR according to the detected genomic profiling
• Duration of response (DOR) [12 months]: to describe duration of response (DOR) according to the detected genomic profilingto describe the genomic profiling according to treatment line (second, third or subsequent) to describe anamnestic characteristics (weight, ECOG PS, sites of metastasis, response to previous treatment lines)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥ 18 years.
* Patients with histological diagnosis of predominantly clear cell carcinoma
* Availability of the tumor tissue from the primary tumor and/or a metastatic site for the genomic profiling analysis not older than 5 years.
* Evaluable disease according to RECIST criteria v 1.1
* Treatment with cabozantinib after one or more previous therapies for mRCC
* Patient progressed from the start to cabozantinib therapy within 3 months or after 9 months
* Any prognosis group according to the IMDC risk score
* Signed informed consent must be obtained for living patients. Patients who died and patient untraceable will be analyzed based on the Authorization no. 9/2016 of the Italian Data Protector Supervisor.

Exclusion Criteria:

* Non-availability of tumor tissue from the primary tumor or a metastatic site for biomarker analysis
* Patient progressed between 3 and 9 months from the beginning of treatment with cabozantinib.
* Non-availability of clinical information useful to evaluate the IMDC risk group at baseline.

• Carmine Pinto, MD, Principal investigator, AUSL/IRCCS of Reggio Emilia
• Cristina Masini, MD, Study chair, AUSL/IRCCS of Reggio Emilia
• Stefania Di Girolamo, MD, Study chair, AUSL/IRCCS of Reggio Emilia