Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: characterization of survival outcome and application of the International mRCC Database Consortium criteria.

BACKGROUND: This study aimed to apply the International mRCC Database Consortium (IMDC) prognostic model in metastatic non-clear cell renal cell carcinoma (nccRCC). In addition, the survival outcome of metastatic nccRCC patients was characterized. METHODS: Data on 2215 patients (1963 with clear-cell RCC [ccRCC] and 252 with nccRCC) treated with first-line VEGF- and mTOR-targeted therapies were collected from the IMDC. Time to treatment failure (TTF) and overall survival (OS) were compared in groups with favorable, intermediate, and poor prognoses according to IMDC prognostic criteria RESULTS: The median OS of the entire cohort was 20.9 months. nccRCC patients were younger (P < .0001) and more often presented with low hemoglobin (P = .014) and elevated neutrophils (P = .0001), but otherwise had clinicopathological features similar to those of ccRCC patients. OS (12.8 vs 22.3 months; P < .0001) and TTF (4.2 vs 7.8 months; P < .0001) were worse in nccRCC patients compared with ccRCC patients. The hazard ratio for death and TTF when adjusted for the prognostic factors was 1.41 (95% CI, 1.19-1.67; P < .0001) and 1.54 (95% CI, 1.33-1.79; P < .0001), respectively. The IMDC prognostic model reliably discriminated 3 risk groups to predict OS and TTF in nccRCC; the median OS of the favorable, intermediate, and poor prognosis groups was 31.4, 16.1, and 5.1 months, respectively (P < .0001), and the median TTF was 9.6, 4.9, and 2.1 months, respectively (P < .0001). CONCLUSIONS: Although targeted agents have significantly improved the outcome of patients with nccRCC, for the majority survival is still inferior compared with patients with ccRCC. The IMDC prognostic model reliably predicts OS and TTF in nccRCC and ccRCC patients.

Real-world data on the efficacy and safety of pazopanib in IMDC favorable- and intermediate-risk metastatic renal cell carcinoma: a multicenter retrospective cohort study of Chinese patients.

Background: Pazopanib was recommended as first-line treatment option for Metastatic renal cell carcinoma (mRCC), while evidence from strictly selected patients has poor external validity and clinical characteristics are complex in real-world clinical practice. This study aimed to illustrate the survival benefits and safety of pazopanib monotherapy using real-world data of mRCC patients. Methods: This was a retrospective, multicenter, cohort study. We recruited adult patients with International Metastatic renal cell carcinoma Database Consortium (IMDC) favorable- and intermediate-risk mRCC receiving first-line pazopanib from May 2017 to February 2020. Patients were treated with pazopanib 800 mg or 600 mg orally once daily. Treatment efficacy, and drug safety were analyzed. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Drug safety was assessed according to the grade of treatment-related adverse reactions. Results: Based on IMDC risk stratification, there were 46 (32.2%) patients in the favorable-risk group and 97 (67.8%) patients in the intermediate-risk group. The median progression-free survival (PFS) of the entire cohort, favorable- and intermediate risk groups was 21.2, 27.1 and 17.2 months, respectively. In the intermediate-risk group, PFS was much longer in patients with 1 risk factor than in patients with 2 risk factors, with a median of 25.9 months versus 11.2 months (P<0.0001). Patients with lung metastasis only had longer PFS than those with bone metastasis only, with a median PFS of 25.9 vs. 21.2 months, respectively. Furthermore, local therapy for the metastatic site appeared to benefit patients in the IMDC favorable-risk group but not those in the IMDC intermediate-risk group. The best response was 40/140 (29%) partial response (PR), 86/140 (61%) stable disease (SD), and 14/140 (10%) progressive disease (PD). The most common adverse drug reactions (ADRs) were change in hair color (47.7%), hypertension (40.0%), diarrhea (40.0%), proteinuria (38.5%), elevation of transaminase (35.4%), and hand-foot skin reaction (32.3%). Conclusions: This real-world data analysis recommended that patients in intermediate-risk group need to be further stratified according to the number of risk factors. Pazopanib was most suitable for patients with lung metastasis only. Local treatment for metastatic lesions should only be recommended in IMDC favorable patients.

Pazopanib in patients with metastatic renal cell carcinoma: a single-center, real-world, retrospective Chinese study.

BACKGROUND: The efficacy and safety of pazopanib in patients diagnosed with metastatic renal cell carcinoma (mRCC) have been demonstrated by a Chinese subgroup analysis of the COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial. However, the real-world data are still unknown. This single-center, retrospective study was designed to verify the real-world effects of pazopanib in Chinese patients with mRCC. METHODS: Patients with mRCC and a clinical decision to initiate pazopanib as first-line therapy were eligible. The primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and safety being evaluated as secondary endpoints. The effectiveness according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model, number of risk factors in the intermediate risk group, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and the number and site of organ metastasis were also assessed. RESULTS: A total of 32 patients were enrolled, including 23 (71.9%) males and 9 (28.1%) females. The median age was 57 years (range 29-75 years). With a median follow-up time of 23.8 months, a median PFS of 18.3 months, and an ORR of 37.5%. Median OS was not reached, and the 1-, 2-, and 3-year overall survival rates were 90.6%, 78.1, and 65.6%, respectively. According to IMDC risk model, 37.5% were placed in the favorable risk (FR) subgroup, 56.2% (the majority) were placed in the intermediate risk (IR) subgroup, and 6.3% were placed in the poor risk (PR) subgroup. Compared with the IR and PR groups, the FR group achieved the best ORR (58.3%) and median PFS (22.1 months). Having 1 risk factor, ECOG PS <2, 1 organ metastasis site, and only lung metastasis associated with a higher ORR and better median PFS. The IMDC risk model and number of metastases were associated with PFS. The most common adverse events were change in hair color (69.0%), diarrhea (63%), and hypertension (50%). CONCLUSIONS: Pazopanib showed efficacy and safety in real-world Chinese mRCC patients.

Outcome of patients with metastatic sarcomatoid renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. RESULTS: Two thousand two hundred eighty-six patients were identified (sRCC: n = 230 and non-sRCC: n = 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P = .018) and third-line (P < .0001) systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P < .0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (hazard ratio, 1.5; P < .0001 for both). CONCLUSION: Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome with targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.