Page 26

30114GA

MEDICAL INTELLIGENCE (continued from page 65) intermediate/poor risk patients, which was 41.6% for the nivolumab/ipilimumab combination compared to 26.5% for sunitinib (P < 0.0001) with 9.4% of patients receiving combination therapy achieving complete response (CR) compared to1.2% of patients on sunitinib. There was an improvement in median PFS with the combination in this cohort; median PFS was 11.6 months for the nivolumab and ipilimumab combination versus 8.4 months with sunitinib, hazard ratio HR 0.82 (P = 0.03). The efficacy outcomes differed according to the levels of PD-L1 expression and IMDC risk group. Both the ORR per independent committee and PFS significantly favored nivolumab plus ipilimumab over sunitinib in intermediate/ poor risk patients having baseline PD-L1 expression ≥1% where the ORR was 58% versus 25%, and median PFS was 22.8 (95% CI 9.4, NR) months versus 5.9 (95% CI 4.4, 7,1) months, respectively, HR 0.48 (95% CI 0.28, 0.82; P = 0.0003). The investigators found that baseline tumor PD-L1 expression was lower in the cohort of patients at favorable risk where 11% of patients on combination had PD-L1 levels ≥1% versus12% of patients on sunitinib compared to 26% versus 29% of patients at intermediate or poor risk in the respective treatment arms. In patients at favorable risk, both the ORR and PFS were higher with sunitinib over combination; in this cohort, ORR was 29% with nivolumab/ipilimumab versus 52% with sunitinib (P = 0.0002) and median PFS was 15.3 (95% CI 9.7, 20.3) months versus 25.1 (95% CI 20.9, NR) months, respectively, HR 2.17 (95% CI 1.46, 3.22; p < 0.0001). In the overall composite of patients at any risk, no significant difference between treatments was demonstrated in ORR (P = 0.0191) or PFS (P = 0.819). Any grade drug-related adverse events (AEs) occurred in 509 (93%) of patients in the nivolumab/ ipilimumab cohort and in 521 (97%) of patients receiving sunitinib. With the combination, 54% of patients had a grade 3 to 4 AE, and with sunitinib 63% of patients had a grade 3 to 5 AE. 82 Kidney Cancer Journal Progression-free Rate Unaffected by Sequence of Cytoreductive Nephrectomy and Sunitinib in Patients with Synchronous mRCC MADRID—Treating primary tumors by administering targeted therapy with sunitinib prior to cytoreductive nephrectomy (CN) did not improve the progression-free rate at 28 weeks over a sequence of immediate CN followed by sunitinib in patients with synchronous metastatic renal cell carcinoma (mRCC), according to findings from a randomized trial presented at ESMO 2017. Axel Bex, Surgical Oncology-Urology, The Netherlands Cancer Institute in Amsterdam, Netherlands and colleagues investigated whether the outcome after sequential cytoreductive nephrectomy (CN) followed by targeted therapy with sunitinib could be improved with the opposite sequence. They randomized 99 patients with mRCC to immediate CN followed by sunitinib (n=50) versus three cycles of sunitinib followed by CN plus sunitinib (n=49). The study (EORTC 30073 SURTIME NCT01099423) included patients with histologically confirmed clear-cell subtype, and a resectable asymptomatic primary tumor plus 3 or fewer surgical risk factors. After 5.7 years the study included 99 patients from 19 institutions. The immediate CN arm had 50 patients and the deferred CN arm had 49 patients. The majority of patients were male in both arms with a median age of 60 compared to 58 years, and MSKCC intermediate risk was reported for 86% versus 87.7% of patients, respectively. In the respective arms, WHO performance status (PS) was 0 and 1 in 72% and 28% versus 63.3 % and 36.7%; 86% versus 93.9% of patients had ≥ 2 measurable metastatic sites and the mean (standard deviation) size of the primary tumor was 93.1 (37.8) mm versus 96.8 (31.3) mm. Patients in each arm derived different benefit from each sequence. At a median follow-up of 3.3 years, 46 of 50 patients underwent CN in the immediate CN arm and 40 of these patients had received post-CN sunitinib. In the deferred CN arm, 48 of 49 patients had been treated with sunitinib prior to CN; of these patients, 40 underwent CN and 26 also received post-CN sunitinib. KCJ


30114GA
To see the actual publication please follow the link above