Índice Melanoma Cáncer de Pulmón Otros tumores Carcinoma de Vejiga Carcinoma de Células Renales Carcinoma de Cabeza y Cuello Carcinomas del tubo digestivo Cáncer de Mama
MELANOMA
CIRUGÍA CIRUGÍA + INFa Tto Sistémico
INMUNOTERAPIA: INHIBIDOR DE CTLA4
Varón 87 años. Melanoma metastásico (cutánides, pulmonares y hepáticas)
Respuesta a Ipilimumab
Respuesta tras Ipilimumab Ipi x 4 ciclos
NIVOLUMAB : FASE 3 1ª linea Nivolumab (N = 210) Dacarbazine (N = 208) ORR, % (95% CI) 40% (33 47%) 14% (10 19%) Best overall response Complete response 8% 1% Partial response 32% 13% Stable disease 17% 22% Progressive disease 33% 49% Unable to determine 11% 15% Robert C. et al NEJM Novenmber 2014
Updated Results From a Phase III Trial of Nivolumab Combined With Ipilimumab in Treatment-naïve Patients With Advanced Melanoma (Checkmate 067) Jedd D. Wolchok, 1 Vanna Chiarion-Sileni, 2 Rene Gonzalez, 3 Piotr Rutkowski, 4 Jean-Jacques Grob, 5 C. Lance Cowey, 6 Christopher D. Lao, 7 Dirk Schadendorf, 8 Pier Francesco Ferrucci, 9 Michael Smylie, 10 Reinhard Dummer, 11 Andrew Hill, 12 John Haanen, 13 Michele Maio, 14 Grant McArthur, 15 Dana Walker, 16 Joel Jiang, 16 Christine Horak, 16 James Larkin, 17* F. Stephen Hodi 18* ASCO 2016
Randomized, double-blind, phase III study to compare NIVO+IPI or NIVO alone to IPI alone Unresectab le or Metatastic Melanoma Previously untreated 945 patients Random ize 1:1:1 Stratify by: Tumor PD-L1 express ion a BRAF mutation status AJCC M stage N = 314 N = 316 N = 315 NIVO 1 mg/kg + IPI 3 mg/kg Q3W for 4 doses then NIVO 3 mg/kg Q2W NIVO 3 mg/kg Q2W + IPImatched placebo IPI 3 mg/kg Q3W for 4 doses + NIVO-matched placebo Treat until progressi on b or unaccept able toxicity a Verified PD-L1 assay with 5% expression level was used for the stratification of patients; validated PD-L1 assay was used for efficacy analyses ASCO 2016 bpatients could have been treated beyond progression under protocol-defined circumstances
RESPUESTA AL TRATAMIENTO a By RECIST v1.1 NR = not reached NIVO + IPI (N = 314) NIVO (N = 316) IPI (N = 315) ORR, % (95% CI) a 57.6 (52.0, 43.7 (38.1, 19.0 (14.9, 63.2) 49.3) 23.8) Two-sided P value vs IPI <0.001 <0.001 -- Best overall response, % 12.1 9.8 2.2 Complete response Partial response 45.5 33.9 16.8 Stable disease 13.1 10.4 21.9 Progressive disease 22.6 38.0 48.9 Unknown 6.7 7.9 10.2 Median duration of response, months (95% CI) Ongoing response among responders, % NR (20.5, 22.3 (20.7, 14.4 (8.3, NR) NR) NR) 72.5 72.4 51.7
Progression-Free Survival (Intent-to- Treat Population) F S P of Progression-free Survival (%) a g e c e n 100 90 80 70 60 50 40 30 20 10 0 NIVO+ IPI NIVO IPI 0 3 6 9 12 15 PFS per Investigator (months) 18 NIVO + IPI (N = NIVO (N = IPI (N = 315) 314) 316) Median PFS, months 11.5 (8.9, 6.9 (4.3, 9.5) 2.9 (2.8, 3.4) (95% CI) 16.7) HR (99.5% CI) vs. IPI 0.42 (0.31, 0.55 (0.43, -- 0.57) a 0.76) a HR (95% CI) vs. NIVO 0.76 (0.60, 0.92) b -- -- 49 % 42 % 18 % 46 % 39 % 14 % 2 1 a Stratified log-rank P<0.00001 vs. IPI Number of patients at risk: Nivolumab + 314 219 174 156 133 126 103 48 8 0 Ipilimumab Nivolum 316 177 148 127 114 104 94 46 8 0 ab Ipilimum 315 137 78 58 46 40 25 15 3 0 ab 2 4 b Exploratory endpoint 2 7
CARCINOMA PULMONAR
CIRUGÍA QT/RT SistémicoPa liativo
NIVOLUMAB FASE 3 CheckMate 017 2ªLINEA NSCLC ( Squamous) ESMO 2015
NIVOLUMAB CheckMate 017 ESMO 2015
NIVOLUMAB CheckMate 057 ESMO 2015
CASO 1. Carcinoma Epidermoide de Pulmón en tratamiento con Nivolumab CASO 2. Adenocarcinoma de Pulmón en tratamiento con Nivolumab
ATEZOLIZUMAB FASE 2 NSCLC Study BIRCH Besse B, et al ESMO 2015
ATEZOLIZUMAB Study BIRCH Besse B, et al ESMO 2015
CARCINOMA RENAL
CA209-025: Phase III, randomized, open-label trial of nivolumab vs everolimus in subjects with advanced or metastatic clear cell RCC who have received prior antiangiogenic therapy N=82 Key Inclusion Criteria 2Advanced/metastatic clear cell RCC No more than 3 total prior regimens in advanced/metastatic setting 1 or 2 prior antiangiogenic therapy regimens in advanced/metastatic setting Karnofsky PS 70% No CNS metastases No prior therapy with mtor inhibitor No autoimmune disease Nivolumab Median OS, months (95% CI) 25.0 (21.8 NE) Everolimus 19.6 (17.6 23.1) Adapted from Motzer et al, 2015, N Engl J Med. R 1:1 Overall Survival (Probability) Nivolumab 3 mg/kg IV q2w Everolimus 10 mg PO qd 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Until progression *, unacceptabl e toxicity, withdrawal of consent, or end of trial Primary Outcome Measure: OS Secondary Outcome Measures: PFS, ORR, duration of objective response, duration of OS by PD-L1 status, safety, disease-related symptom progression rate Everolimus Nivolumab 0.0 0 3 6 9 12 15 18 21 24 27 30 33 Months # of patients at risk Nivolumab 410 389 359 337 305 275 213 139 73 29 3 0 Everolimus 411 366 324 287 265 241 187 115 61 20 2 0 CNS = central nervous system; IV = intravenous; mtor = mammalian target of rapamycin; ORR = objective response rate; OS = overall survival; PD-L1 = programmed death ligand-1; PFS = progression-free survival; PO = by mouth; PS = performance status; q2w = every 2 weeks; R = randomized; RCC = renal cell carcinoma.
CA209-025: Phase III, randomized, open-label trial of nivolumab vs everolimus in subjects with advanced or metastatic clear cell RCC who have received prior antiangiogenic therapy Survival benefit with nivolumab was irrespective of PD-L1 expression Overall Survival (Probability) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Everolimus PD-L1 1% (n = 24%) PD-L1 <1% (n = 76%) Median OS, months (95% CI) Nivolumab 21.8 (16.5 28.1) Everolimus 18.8 (11.9 19.9) Nivolumab 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Median OS, months (95% CI) Nivolumab 27.4 (21.4 NE) Everolimus 21.2 (17.7 26.2) Everolimus Nivolumab 0.0 0 3 6 9 12 15 18 21 24 27 30 33 Months # of patients at risk Nivolumab 94 86 79 73 66 58 45 31 18 4 1 0 Everolimus 87 77 68 59 52 47 40 19 9 4 1 0 0.0 0 3 6 9 12 15 18 21 24 27 30 33 Months 276 265 245 233 210 189 145 94 48 22 2 0 299 267 238 214 200 182 137 92 51 16 1 0 Adapted from Motzer et al, 2015, N Engl J Med. Based on data cut-off of June 2015. CI = confidence interval; HR = hazard ratio; NE = not estimable; mrcc = metastatic renal cell carcinoma; OS = overall survival; PD-L1 = programmed death ligand
CARCINOMA UROTELIAL
Efficacy<br />Reduction in Tumor Burden Presented By Robert Dreicer at 2016 ASCO Annual Meeting
Efficacy<br />Time to Response Presented By Robert Dreicer at 2016 ASCO Annual Meeting
Efficacy<br />Duration of Treatment and Response Presented By Robert Dreicer at 2016 ASCO Annual Meeting
IMvigor210 Study: Cohort 1 Presented By Arjun Balar at 2016 ASCO Annual Meeting
Baseline Characteristics<br />Representative of the cisplatin-ineligible population Presented By Arjun Balar at 2016 ASCO Annual Meeting
Efficacy<br />Response to Atezolizumab (IRF RECIST v1.1) Presented By Arjun Balar at 2016 ASCO Annual Meeting
Efficacy<br />Change in Tumor Burden Presented By Arjun Balar at 2016 ASCO Annual Meeting
Efficacy<br />Response by Baseline Characteristic Presented By Arjun Balar at 2016 ASCO Annual Meeting
Efficacy<br />Overall Survival (Median and Landmark 12-Month OS) Presented By Arjun Balar at 2016 ASCO Annual Meeting
Efficacy<br />Overall Survival (Median OS) by PD-L1 Status Presented By Arjun Balar at 2016 ASCO Annual Meeting
CARCINOMA CABEZA Y CUELLO
Próximas indicaciones de Anti-PDL1/Anti-PD1 Hodgkin Lymphoma 1 Hepatocellular Carcinoma 2 Ovarian Cancer 3 Urothelial Cancer 4 Small Cell Lung Cancer 5 (Nivolumab 1 mg/kg BW + Ipilimumab 3 mg/kg BW) Colorectal Cancer MSI-H 6 (Nivolumab 3 mg/kg BW + Ipilimumab 1 mg/kg BW) Gastric Cancer 7 (Nivolumab 1 mg/kg BW + Ipilimumab 3 mg/kg BW) Esophageal Cancer 8 Younes et al. Oral presentation at ASCO 2016, Abstract 7535. Sangro et al. Oral presentation at ASCO 2016, Abstract 4078. Hamanishi et al. J Clin Oncol. 2015, 33(34): 4015-22. Sharma et al. Oral presentation at ASCO 2016, Abstract 4501. Antonia et al. Oral presentation at ASCO 2016, Abstract 100. Overman et al. Oral presentation at ASCO 2016, Abstract 3501. Janjigian et al. Oral presentation at ASCO 2016, Abstract 4010. Ura et al. Poster presentation at ESMO 2015, Abstract 2301
MUCHAS GRACIAS