Prognostic Stratification by the Meet-URO Score in Real-World Older Patients With Metastatic Renal Cell Carcinoma (mRCC) Receiving Cabozantinib: A Subanalysis of the Prospective ZEBRA Study (Meet-URO 9).

BACKGROUND: The addition of neutrophil to lymphocyte ratio (NLR) and bone metastases to the IMDC classification provided by the Meet-URO score, resulted in higher prognostic accuracy in metastatic renal cell carcinoma (mRCC) patients receiving ≥2nd line nivolumab or cabozantinib in 2 retrospective analyses and 1st line nivolumab-ipilimumab in an expanded access programme. Prognostic estimates for older mRCC patients might be key for clinical decision-making. METHODS: The outcome of real-world older (≥70 years) mRCC patients treated with any line cabozantinib within the multicenter observational prospective ZEBRA (Meet-URO 9) study was analyzed according to the baseline Meet-URO score. The primary endpoint was overall survival (OS). The discriminative ability by Harrell's c-index and calibration were assessed to compare the Meet-URO and IMDC scores. RESULTS: A total of 104 mRCC patients received cabozantinib as 1st (38%), 2nd (20%), or ≥3rd (41%) line. With a median follow-up of 11.2 months, the median OS (mOS) was of 18.4 months. According to the IMDC score, favorable (15%), intermediate (65%) and poor-risk (19%) patients had a mOS not reached, of 15.6 and 5.7 months respectively (p = .011). According to the Meet-URO score groups, mOS was not reached in both group 1 (10%) and group 2 (25%), while in group 3 (33%), group 4 (25%) and group 5 (8%) mOS was of 13.6, 12.5, and 3.7 months, respectively (p < .001). The discriminative ability of the Meet-URO score was maintained by merging groups 1 to 2 vs. 3 to 4 vs. 5 (p < .001). The Meet-URO score (with either the original 5-group stratification or the modified 3-group one) showed higher accuracy than the IMDC score (c-index of 0.686 and 0.676 vs. 0.622). CONCLUSION: This analysis confirmed the prognostic accuracy of the Meet-URO score in older mRCC patients treated with cabozantinib and its role as a convenient tool for informing the patient and clinical decisions.

Advanced Non-Clear Cell Renal Cell Carcinoma Treatments and Survival: A Real-World Single-Centre Experience.

BACKGROUND: Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of cancer. Treatment recommendations are extrapolated from ccRCC and lack solid evidence. Here, we review advanced nccRCC patients treated at our institute. PATIENTS AND METHODS: We collected retrospective data on all advanced nccRCC pts treated at the Istituto Oncologico Veneto from January 2008. We compared overall response rate (ORR), progression free survival (PFS) and overall survival (OS) according to histological subtypes and type of systemic treatments. Kaplan-Meier method, log-rank test and Cox regression were used to estimate and compare PFS and OS. RESULTS: Of 1370 RCC patients, 289 had a diagnosis of nccRCC and 121 were eligible for the analysis. Fifty-three pts showed papillary histology (pRCC), 15 chromophobe; 37 unclassified RCC (NOS-RCC), 16 other histologies. Pts with chromophobe and other hystologies showed poorer survival rates compared to pRCC and NOS-RCC (mOS 10.7 vs. 20.7 vs. 30.7, p = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, p = 0.10), PFS (12.7 vs. 6.4, p = 0.10) and ORR (42.4% vs. 13.9%, p = 0.002) than those treated with monotherapy. IMDC and Meet-URO score retained their prognostic value. CONCLUSION: Our retrospective real-life cohort of advanced nccRCC patients shows that immunotherapy-based combinations could improve ORR, PFS and OS compared to TKI monotherapy. Prospective trials for nccRCC patients utilizing novel therapies are ongoing and their results eagerly awaited.

Real-World Treatment with Nivolumab or Cabozantinib for Metastatic Renal Cell Carcinoma (mRCC) in the Veneto Region of Italy: Results of AMOUR Study.

BACKGROUND: Second- or third-line treatment options for metastatic renal cell carcinoma (mRCC) have dramatically changed in the last few years. There are no criteria for the choice between nivolumab and cabozantinib, which both demonstrated overall survival (OS) gain in pivotal trials. OBJECTIVE: We conducted an analysis of oncological outcomes in patients treated in the Veneto Region (Italy), studying different sequences of TKI-nivolumab-cabozantinib or TKI-cabozantinib-nivolumab in a publicly funded healthcare system. PATIENTS AND METHODS: We conducted a retrospective, real-world analysis of all consecutive patients with mRCC treated with nivolumab or cabozantinib in 2017-2018 at 19 Oncology Units in the Veneto Region. RESULTS: We identified 170 patients, 73 % males, median age 68.4 years. All patients started second-line treatment, 59 % received a third-line therapy. Patients with NLR > 3 had a shorter OS (p < 0.0001). In the second-line treatment, nivolumab was administered to 108 patients (63 %), cabozantinib to 29 (17 %); in the third-line treatment nivolumab was administered to 42 patients (25 %), cabozantinib to 49 (29 %). Median OS and PFS in second line treatment were 28.4 and 6.6 months for nivolumab, 16.8 and 6.6 months for cabozantinib. Median OS and PFS in third-line treatment were 27 and 5.2 months for nivolumab, 16.6 and 7.5 months for cabozantinib. Median OS for nivolumab>cabozantinib sequence versus cabozantinib > nivolumab was 28.8 versus 19.9 months (p = 0.2); median PFS for both the sequences were similar at 5.7 months. A cost effectiveness per month of survival of the two sequences analysis was performed: the cost per month for the nivolumab > cabozantinib sequence was 1738.60whereas the cost for the other one was €1624.80. CONCLUSIONS: In our real-world cohort, most patients received nivolumab as second-line treatment. Outcomes of single drugs are superimposable with those in the published literature. Both the sequences of nivolumab and cabozantinib appear to be viable, effective strategies from an OS and cost-effective perspective.