Inmunoterapia en cáncer de cabeza y cuello
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Cirugía de cabeza y cuello, Bogotá, 07.11.2019
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Inmunoterapia en cáncer de cabeza y cuello
- 1. CM-141/KN-040/KN-048 Entendiendo la inmunoterapia y sus indicaciones en la patología oncológica de cabeza y cuello Inspirado en: Armin Hofman, 1959, Cartel Giselle
- 2. Mauricio Lema Medina MD Clínica de Oncología Astorga / Clínica SOMA Medellín Inspirado en: Michael Bierut, 2013, Logo para Mohawk Fine Papers
- 3. 3 Conflicts of interest for this talk Mauricio Lema Medina BMS/MSD @Onconerd
- 4. Onconerd
- 5. Alexandrov LB, NATURE 2013 SOMATIC MUTATION PREVALENCE
- 10. Célula tumoral Célula Dendrítica Antígeno tumoral Linfocito T CD8+/Citotóxico Receptor de célula T (TCR) MHC II y antígeno MHC II: Major histocompatibility complex
- 11. T-Cell activation Célula tumoral Célula DendríticaLinfocito T CD8+/Citotóxico Co-estimuladora CD28 Co-estimuladora B7.1 (CD80/86)
- 12. Célula tumoral Célula DendríticaLinfocito T CD8+/Citotóxico CTLA-4 Co-estimuladora B7.1 (CD80/86) T-Cell brake
- 13. Célula tumoral Célula DendríticaLinfocito T CD8+/Citotóxico CTLA-4 Co-estimuladora B7.1 (CD80/86) T-Cell brake Anti-CTLA-4
- 14. Célula tumoral Célula DendríticaLinfocito T CD8+/Citotóxico CTLA-4 Co-estimuladora B7.1 (CD80/86) Restablishes T-Cell functionality Anti-CTLA-4
- 16. Tumor Cell CD8+ T-Cell MHC class I + Ag T-Cell receptor) +++
- 17. Effector T- Cell activation Célula tumoral CD8+ T-Cell MHC class I + Ag T-Cel receptor +++
- 19. Tumor PD-L1 (PD- L2) expression occurs when there is continuous Gamma IFN exposure Célula tumoral Linfocito T CD8+/Citotóxico IFN-γ IFN-γR PD-L1 PD-1 - - - Anti tumor immunity Brake
- 20. Célula tumoral Linfocito T CD8+/Citotóxico PD-L1 PD-1 - - - Anti-PD1
- 22. Célula tumoral Linfocito T CD8+/Citotóxico PD-L1 PD-1 - - - Anti-PD-L1
- 24. Design N Scenario Nivolumab (CM-141) Phase III 361 After platin Pembrolizumab (KN-040) Phase III 495 After platin Pembrolizumab (KN-048) Phase III 882 First-line recurrente and/or metastatic PHASE III TRIALS Ferris et al. NEJM 2016, Cohen et al. Lancet 2019, Burtness et al. ESMO 2018, Rischin et al. ASCO 2019
- 25. Key Elegibility Criteria R/M SCCHN of the oral cavity, pharynx, or larynx Progression on or within 6 months of last dose of platinum-based therapy Irrespective of number of prior lines of therapy Documentation of p16 to determine HPV status (oropharyngeal cancer only) Stratificaion factor Prior cetuximab treatment R 2:1 Nivolumab 3 mg/kg q2w Investigator’s choice Methotrexate or Docetaxel or Cetuximab Primary endpoint OS Other endpoints PFS ORR … CHECKMATE 141 STUDY DESIGN Ferris et al. NEJM 2016.
- 26. CHECKMATE 141 OVERALL SURVIVAL Ferris et al. NEJM 2016. 12-mo OS 18-mo OS Nivolumab 34.0% 21.5% SOC 19.7% 8.3%
- 27. CHECKMATE 141 OVERALL SURVIVAL BY PD-L1 Ferris et al. NEJM 2016.
- 28. Ferris et al. NEJM 2016. CHECKMATE 141 OVERALL SURVIVAL BY PD-L1
- 29. CHECKMATE 141 QUALITY OF LIFE Ferris et al. NEJM 2016.
- 30. CHECKMATE 141 ADVERSE EVENTS Ferris et al. NEJM 2016.
- 31. Key Elegibility Criteria SCC of the oral cavity, pharynx or larynx Progressive disease after platinum-containing regimen ECOG PS 0-1 R 1:1 Pembrolizumab 200 mg IV Q3W for 2 y Investigator’s choice Methotrexate or Docetaxel or Cetuximab KEYNOTE 040 STUDY DESIGN Primary endpoint OS Cohen et al. Lancet 2019 N: 495
- 32. KEYNOTE 040 - RESULTS Cohen et al. Lancet 2019 Median OS Pembrolizumab: 8.4 months Standard-of-care: 6.9 months
- 33. KEYNOTE 040 - RESULTS Cohen et al. Lancet 2019
- 34. KEYNOTE 040 - ADVERSE EVENTS Cohen et al. Lancet 2019
- 35. KEYNOTE 040 - ADVERSE EVENTS Cohen et al. Lancet 2019
- 37. First-Line R/M disease incurable by local therapy R 1:1:1 Pembrolizumab 200 mg IV Q3W for 2 y KEYNOTE 048 STUDY DESIGN Primary endpoint OS Pembrolizumab + Platinum + FU Cetuximab + Platinum + FU Burtness et al. ESMO 2018
- 38. First-Line R/M disease incurable by local therapy R 1:1:1 Pembrolizumab 200 mg IV Q3W for 2 y KEYNOTE 048 STUDY DESIGN Primary endpoint OS Pembrolizumab + Platinum + FU Cetuximab + Platinum + FU Burtness et al. ESMO 2018
- 39. First-Line R/M disease incurable by local therapy R 1:1:1 Pembrolizumab 200 mg IV Q3W for 2 y KEYNOTE 048 STUDY DESIGN Primary endpoint OS Cohen et al. Lancet 2019 Pembrolizumab + Platinum + FU Cetuximab + Platinum + FU
- 40. First-Line R/M disease incurable by local therapy R 1:1:1 Pembrolizumab 200 mg IV Q3W for 2 y KEYNOTE 048 STUDY DESIGN Primary endpoint OS Pembrolizumab + Platinum + FU Cetuximab + Platinum + FU Not in the study design Burtness et al. ESMO 2018
- 42. CPS (Combined Positive Score) CPS = Number of PD-L1 stained cells (Tumor cells, lymphocytes, macrophages) Total number of viable tumor cells x100 CO-PRIMARY ENDPOINTS OS and PFS for the total population, CPS ≥20, CPS ≥1
- 44. Burtness et al. ESMO 2018
- 45. Burtness et al. ESMO 2018
- 46. Burtness et al. ESMO 2018
- 47. OS, P vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting
- 48. KEYNOTE 048 ORR ORR Pembrolizumab EXTREME Total population 17% 36% CPS ≥1% 19% 35% CPS ≥20% 23% 36% Burtness et al. ESMO 2018
- 49. KEYNOTE-048 Study Design (NCT02358031) Presented By Danny Rischin at 2019 ASCO Annual Meeting
- 50. OS, P+C vs E, CPS ≥20 Population Presented By Danny Rischin at 2019 ASCO Annual Meeting
- 51. OS, P+C vs E, CPS ≥1 Population Presented By Danny Rischin at 2019 ASCO Annual Meeting
- 52. OS, P+C vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting
- 53. OS, P+C vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting
- 54. OS, P+C vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting
- 55. Patients in stable condition and asymptomatic Do PD-L1 CPS ≥20%1%-20%≤1% Pembrolizumab Pembrolizumab +/- Chemotherapy Cetuximab + Chemotherapy 40-45%35-40%15%
- 56. Patients in stable condition and asymptomatic Do PD-L1 CPS ≥20%1%-20%≤1% Pembrolizumab Pembrolizumab +/- Chemotherapy Cetuximab + Chemotherapy 40-45%35-40%15%
- 57. Rapid shrinkage needed CPS available? No≥1%≤1% Pembrolizumab + Chemotherapy Pembrolizumab +/- Chemotherapy Cetuximab + Chemotherapy
- 58. Rapid shrinkage needed CPS available? No≥1%≤1% Pembrolizumab + Chemotherapy Pembrolizumab +/- Chemotherapy Cetuximab + Chemotherapy
- 59. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
- 60. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
- 61. CHALLENGES Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
- 62. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm CHALLENGES
- 63. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm CHALLENGES
- 64. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
- 65. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
- 66. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
- 67. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
- 68. ACCESS
- 69. Lema M, unpublished (2019) Long-Term Survival After Definitive Radiotherapy Combined With Systemic Therapy In Locally-Advanced Head and Neck Squamous Cell Carcinoma in a Single Practice in Medellín, Colombia
- 70. Lema M, unpublished (2019) Long-Term Survival After Definitive Radiotherapy Combined With Systemic Therapy In Locally-Advanced Head and Neck Squamous Cell Carcinoma in a Single Practice in Medellín, Colombia
- 71. REGULATORY Inspirado en: Josef Albers, 1967, Homenaje al cuadrado
- 72. Pembrolizumab Melanoma mHNSCCNSCLC Urothelial INVIMA NO INVIMA Metastatic Metastatic First-line and second-line Metastatic second-line Nivolumab Melanoma mHNSCCNSCLC Renal Adjuvant Metastatic Metastatic second-line Metastatic second-line Metastatic second-line Not approved KN-040/KN-048 CM-141
- 73. Biomarker assessment Inspirado en: Josef Albers, 1967, Homenaje al cuadrado
- 74. NSCLC HNSCC PD-L1 POSITIVITY VARIES FROM TUMOR TO TUMOR Only PD-L1 expressed on tumor cells PD-L1 expressed on tumor cells and tumor-associated immune cells
- 75. @onconerd Inspirado en: Michael Bierut, 2013, Logo para Mohawk Fine Papers