INMUNOTERAPIA: NUEVO PARADIGMA EN LOS TUMORES DE CABEZA Y CUELLO Dra. Lara Iglesias H.U.12 Octubre
INTRODUCCIÓN INFORME SEOM DE EVALUACIÓN DE FÁRMACOS: NIVOLUMAB EN CÁNCER EPIDERMOIDE DE CABEZA Y CUELLO
INTRODUCCIÓN
PRESENTE
PRESENTE 2ª LÍNEA NO estandar en tratamiento hasta 2016
PRESENTE
CheckMate 141 Randomized, global, phase 3 trial of the efficacy and safety of nivolumab versus single-agent therapy of investigator s choice in patients with R/M SCCHN (n=361) Key Eligibility Criteria n=240 R/M SCCHN of the oral cavity, pharynx, or larynx Not amenable to curative therapy Progression on or within 6 months of last dose of platinum-based therapy ECOG PS 0 1 No active CNS metastases No prior targeted therapy toward T- cell co-stimulating or immune checkpoints Stratification factor Prior cetuximab treatment R 2:1 Nivolumab 3 mg/kg IV q2w n=121 Investigator s Choice Methotrexate 40-60 mg/m² IV weekly Docetaxel 30-40 mg/m² IV weekly Cetuximab 400 mg/m² IV once, then 250 mg/m² weekly Primary endpoint OS Other endpoints PFS ORR TTR Safety Biomarkers Quality of life See notes for footnotes and abbreviations
PRESENTE
OS (%) CheckMate 141: Overall Survival 100 90 80 70 60 50 40 30 20 10 0 No. at risk Median OS, mo (95% CI) Nivolumab (240) 7.5 (5.5, 9.1) 0.70 Investigator s choice (121) 5.1 (4.0, 6.0) (0.51, 0.96) HR (97.73% CI) P value 0 3 6 9 12 26.8) 15 18 Months Nivolumab 240 167 109 52 24 7 0 Investigator s choice 1-year OS rate (95% CI) 36.0% (28.5, 43.4) 16.6% (8.6, 121 87 42 17 5 1 0.0101 Nivolumab Investigator s choice 0 10
Progression-free Survival (%) 100 90 80 70 60 50 40 30 Progression-Free Survival No. of Patients No. of Events Median PFS mo (95% CI) Nivolumab 240 190 2.0 (1.9 2.1) Standard Therapy 121 103 2.3 (1.9 3.1) Hazard ratio for death, 0.89 (95% CI, 0.70 1.13), P=0.32 No. at Risk Nivolumab Standard Therapy 20 10 0 Standard Therapy 0 3 6 9 12 15 18 Months 240 79 32 12 4 1 0 121 43 9 2 0 0 Nivolumab 0 The estimated 6-month PFS rates were 19.7% for nivolumab and 9.9% for standard therapy See notes for abbreviations
Objective Response Rate Nivolumab (n=240) Standard Therapy (n=121) Objective response rate, n (%) 32 (13.3) 7 (5.8) 95% CI 9.3 18.3 2.4 11.6 Best overall response, n (%) Complete response 6 (2.5) 1 (0.8) Partial response 26 (10.8) 6 (5.0) Stable disease 55 (22.9) 43 (35.5) Progressive disease 100 (41.7) 42 (34.7) Not determined 53 (22.1) 29 (24.0) Time to response, mo Median (range) 2.1 (1.8 7.4) 2.0 (1.9 4.6) See notes for reference and abbreviations
Change From Baseline in Sum of Target Lesions (%) Change From Baseline in Sum of Target Lesions (%) Change From Baseline in Sum of Target Lesions (%) Change From Baseline in Sum of Target Lesions (%) CHANGE IN TUMOR BURDEN OVER TIME* Nivolumab 100 Responders 100 75 75 Standard Therapy Responders 50 50 25 25 0 0-25 -25-50 -50-75 -75-100 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 Weeks 100 Stable Disease 75-100 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 Weeks 100 Stable Disease 75 50 50 25 25 0 0-25 -25-50 -50-75 -75-100 -100 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 Weeks 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 Weeks 1 st occurrence of new lesion Off treatment Time of first response Tumor reductions were more durable with nivolumab, shown as tumor-burden plots over time for patients who had either a partial response or a complete response See notes for footnotes
Overall Survival (%) Overall Survival by PD-L1 Expression PD-L1 Baseline 1% PD-L1 Baseline <1% No. of Patients No. of Deaths Median OS mo (95% CI) No. of Patients No. of Deaths Median OS mo (95% CI) Nivolumab 88 49 8.7 (5.7 9.1) Nivolumab 73 45 5.7 (4.4 12.7) 100 Standard Therapy 61 45 4.6 (3.8 5.8) 100 Standard Therapy 38 25 5.8 (4.0 9.8) 90 80 70 60 50 Hazard ratio for death, 0.55 (95% CI, 0.36 0.83) 90 Hazard ratio for death, 0.89 (95% CI, 0.54 1.45) 80 70 60 50 40 40 30 Nivolumab 30 Nivolumab 20 20 No. at Risk Nivolumab Standard Therapy 10 0 Standard Therapy 0 3 6 9 12 15 18 Months 88 67 44 18 6 0 61 42 20 6 2 0 10 0 Standard Therapy 0 3 6 9 12 15 18 Months 73 52 33 17 8 3 0 38 29 14 6 2 0 0 Estimates for OS HR for PD-L1 expression levels of 5% and 10% are similar to those for 1% See notes for abbreviations
Mean Change From Baseline (95% CI) Worse Better QoL: EORTC QLQ-H&N35 Symptom Burden 30 20 Pain Sensory Problems Social Contact Problems 10 MID P < 0.001 P = 0.022 P = 0.012 P < 0.001 P = 0.258 P = 0.001 0-10 MID -20-30 9 15 9 15 9 15 Week Nivolumab Investigator's 15 choice
QoL: EORTC QLQ-C30 Time to Deterioration (Functioning) Nivolumab resulted in more than doubling of time to deterioration for most functional domains Global health/qol Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Median Time to Deterioration (95% CI), mo Nivo 7.7 (5.4, 13.3) IC 3.0 (2.1, 6.1) 7.8 (6.7, NR) 3.6 (2.4, 6.3) 8.6 (5.4, NR) 3.8 (2.6, 7.6) 6.7 (5.4, NR) 4.7 (3.3, NR) 7.8 (5.6, NR) 3.3 (2.4, 6.1) 7.7 (5.4, NR) 3.0 (2.1, 4.7) Favors Nivo Favors IC 0 0,5 1 1,5 2 Hazard Ratio (95% CI) 16
Treatment related AE in 5% of Patients Event Nivolumab (n=236) Standard Therapy (n=111) Any grade Grade 3 or 4 Any grade Grade 3 or 4 number of patients (percent) Any event 139 (58.9)* 31 (13.1) 86 (77.5) 39 (35.1) Fatigue 33 (14.0) 5 (2.1) 19 (17.1) 3 (2.7) Nausea 20 (8.5) 0 23 (20.7) 1 (0.9) Rash 18 (7.6) 0 5 (4.5) 1 (0.9) Decreased appetite 17 (7.2) 0 8 (7.2) 0 Pruritus 17 (7.2) 0 0 0 Diarrhea 16 (6.8) 0 15 (13.5) 2 (1.8) Anemia 12 (5.1) 3 (1.3) 18 (16.2) 5 (4.5) Asthenia 10 (4.2) 1 (0.4) 16 (14.4) 2 (1.8) Vomiting 8 (3.4) 0 8 (7.2) 0 Dry skin 7 (3.0) 0 10 (9.0) 0 Stomatitis 5 (2.1) 1 (0.4) 10 (9.0) 3 (2.7) Weight loss 4 (1.7) 0 6 (5.4) 0 Mucosal inflammation 3 (1.3) 0 14 (12.6) 2 (1.8) Peripheral neuropathy 1 (0.4) 0 7 (6.3) 0 Alopecia 0 0 14 (12.6) 3 (2.7) Neutropenia 0 0 9 (8.1) 8 (7.2) Treatment-related adverse event rates of any grade were similar in the two groups, and fewer grade 3 or 4 events were reported in the nivolumab group than in the standard-therapy group See notes for footnotes
FUTURO
FUTURO 1ª Línea: DURVALUMAB +/- TREMELIMUMAB PEMBROLIZUMAB +/- PLATINO NIVOLUMAB + IPILIMUMAB PEMBRO/NIVO + EPACADOSTAT 2ªLínea: DURVALUMAB +/- TREMELIMUMAB DURVALUMAB +/- AZD9150 ATEZOLIZUMAB QTRT: CISPLATINO + PEMBROLIZUMAB CETUXIMAB + DURVALUMAB INDUCCIÓN
CASO CLÍNICO 3ª LÍNEA (9s) NIVOLUMAB
NIVOLUMAB: 3mg/kg peso basal EVOLUCIÓN: EFICACIA Y CALIDAD DE VIDA RESPUESTA PARCIAL MANTENIDA a todos los niveles 2 años
CONCLUSIONES QUIMIOTERAPIA TERAPIAS DIRIGIDAS - Platinos - Antimetabolitos - Taxanos - - Cetuximab INMUNOTERAPIA Aumentar la - Afatinib supervivencia? - Monoterapia de los pacientes ANTIcon cáncer escamoso de PD1 cabeza y cuello recurrente/metastásico
GRACIAS! laraiglesias@hotmail.com