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A pilot randomized study evaluating nivolumab (nivo) or nivo + bevacizumab (bev) or nivo + ipilimumab (ipi) in patients with metastatic renal cell carcinoma (MRCC) eligible for cytoreductive nephrectomy (CN), metastasectomy (MS) or post-treatment biopsy (Bx).
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2018
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Surgical OncologyImmunodeficienciesImmunologyImmunoeditingImmune SignaturesSurgeryImmunotherapeuticsImmunotherapyTranslational MedicineGenitourinary CancerMetronomic TherapyTumor ImmunityClinical TrialsRandomized TrialRadiation OncologyCancer ResearchHealth SciencesPost-treatment BiopsyMedicineImmune SurveillanceCytoreductive NephrectomyT Cell ActivationUrologyCancer ImmunosurveillanceImmune Checkpoint InhibitorOncology
4520 Background: Since ipi and nivo use distinct mechanisms for T cell activation and bev promotes antigen presentation, we hypothesize that nivo+bev or nivo+ipi would safely lead to measurable immunologic changes and improved clinical activity in MRCC. Methods: In this open-label, randomized trial (NCT02210117), adults with MRCC w/o prior immune checkpoint therapy and anti-VEGF therapy were enrolled and randomized 2:3:2 to receive nivo, nivo+bev or nivo+ipi, followed by surgery (CN or MS), or Bx, and subsequent nivo maintenance therapy up to 2 years. Response was assessed at ≥12 weeks. Pre- and post-treatment blood and tumors were obtained for correlative studies. Results: One hundred patients have been accrued and 90 are evaluable for responses (table below, W = withdrawal; BOR = Best overall response; BRES = Best Response excluding surgical effect). Clinical trial information: NCT02210117. BOR was 50% complete response (CR) + partial response (PR) nivo, 48% CR+PR nivo+bev, 39% CR+PR nivo+ipi. For patients getting surgery, BOR was: 77% nivo, 93% nivo+bev, and 70% nivo+ipi. Grade 3 or 4 toxicities were 30% for nivo, 45% for nivo+bev (including 18% bev-specific hypertension), and 57% for nivo+ipi. We identified a number of immune signatures in relation to clinical responses. Conclusions: Patients able to stay on therapy and receive surgery had BOR ranging from 70%-93%. Combination therapy nivo ± [bev or ipi] plus cytoreductive surgery deserves to be tested in a larger phase 3 trial for MRCC. We will also report correlative biomarker data. Nivo (N = 26) Nivo+Bev (N = 38) Nivo+Ipi (N = 26) CR PR SD PD W CR PR SD PD W CR PR SD PD W All Patients BOR 1 (4%) 12 (46%) 5 (19%) 7 (27%) 1 (4%) 1 (3%) 17 (45%) 7 (18%) 11 (29%) 2 (5%) 1 (4%) 9 (35%) 2 (8%) 13 (50%) 1 (4%) BRES 0 10 (38%) 8 (31%) 7 (27%) 1 (4%) 0 14 (37%) 11 (29%) 11 (29%) 2 (5%) 0 7 (27%) 4 (15%) 14 (54%) 1 (4%) Patients with Surgery BOR 1 (8%) 9 (69%) 2 (15%) 1 (8%) 0 1 (8%) 11 (85%) 1 (8%) 0 0 1 (10%) 6 (60%) 2 (20%) 1 (10%) 0 BRES 0 7 (54%) 5 (38%) 1 (8%) 0 0 8 (62%) 5 (38%) 0 0 0 4 (40%) 4 (40%) 2 (20%) 0 Patients without Surgery BOR 0 3 (23%) 3 (23%) 6 (46%) 1 (8%) 0 6 (24%) 6 (24%) 11 (44%) 2 (8%) 0 3 (19%) 0 12 (75%) 1 (6%)