The Evolution of Nephrectomy and Patient Characteristics in Metastatic Renal Cell Carcinoma Patients Enrolled Into First-Line Tyrosine Kinase Inhibitors Clinical Trials.
The objective of this study was to compare rates of nephrectomy (Nx) in, and characteristics of, patients with metastatic renal cell carcinoma (mRCC) enrolled in prospective clinical trials of tyrosine kinase inhibitors (TKIs) that were completed through (Group 1) versus after (Group 2) 2007.



Searching online databases, we retrospectively identified phase I to III trials with ≥ 15 patients with mRCC treated with first-line TKIs, alone or in combination with other agent(s).



Of 70 trials identified, 42 were included in the analysis (n = 6074 patients). Compared with Group 1, Group 2 patients had significantly less Nx (85.7% vs. 93.7%; P < .001) and prior cytokine therapy (11.1% vs. 46.8%; P < .001). Group 2 also had significantly fewer patients with good prognostic risk (based on Memorial Sloan-Kettering Cancer Center criteria) or performance status (both P < .001). Group 2 patients had a significantly greater objective response rate than Group 1 patients (intent-to-treat analysis: 28.6% vs. 23.1%, respectively; P < .001), whereas Group 1 patients had significantly more stable disease. Clinical benefit was similar in both groups (P = .157), and the means of median progression-free survival were comparable (8.2 and 9.0 months in Groups 1 and 2, respectively; P = .2528).



Use of Nx in mRCC patients participating in clinical trials has declined in the TKI era. More patients with worse prognostic risk profiles are participating in first-line TKI trials after 2007, but objective response rates are higher. Despite patient characteristics that favor the earlier group, progression-free survival is similar as TKIs have replaced cytokines as first-line therapy.
Department of Oncology, Sackler School of Medicine, Tel-Aviv University, Asaf Harofeh Medical Center, Zerifin, Israel. Electronic address: a_sella@asaf.health.gov.il.
Avishay
A
Sella
Department of Oncology, Pfizer, New York, NY.
Kongming
K
Wang
Department of Oncology, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel.
Tal
T
Sella
D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D009362:Neoplasm Metastasis; D009392:Nephrectomy / Q000706:statistics & numerical data*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors
Characterictics; Prognostic; Renal cell cancer; Surgery; Targeted agents