INMUNOTERAPIA: NUEVO PARADIGMA EN LOS TUMORES DE CABEZA Y CUELLO. Dra. Lara Iglesias H.U.12 Octubre

Size: px

Start display at page:

Download "INMUNOTERAPIA: NUEVO PARADIGMA EN LOS TUMORES DE CABEZA Y CUELLO. Dra. Lara Iglesias H.U.12 Octubre"

Mae Dorsey
6 years ago
Views:

1 INMUNOTERAPIA: NUEVO PARADIGMA EN LOS TUMORES DE CABEZA Y CUELLO Dra. Lara Iglesias H.U.12 Octubre

2 INTRODUCCIÓN INFORME SEOM DE EVALUACIÓN DE FÁRMACOS: NIVOLUMAB EN CÁNCER EPIDERMOIDE DE CABEZA Y CUELLO

3 INTRODUCCIÓN

4 PRESENTE

5 PRESENTE 2ª LÍNEA NO estandar en tratamiento hasta 2016

6 PRESENTE

7 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 mg/m² IV weekly Docetaxel 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

8 PRESENTE

9 OS (%) CheckMate 141: Overall Survival 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 ) Months Nivolumab Investigator s choice 1-year OS rate (95% CI) 36.0% (28.5, 43.4) 16.6% (8.6, Nivolumab Investigator s choice 0 10

10 Progression-free Survival (%) Progression-Free Survival No. of Patients No. of Events Median PFS mo (95% CI) Nivolumab ( ) Standard Therapy ( ) Hazard ratio for death, 0.89 (95% CI, ), P=0.32 No. at Risk Nivolumab Standard Therapy Standard Therapy Months Nivolumab 0 The estimated 6-month PFS rates were 19.7% for nivolumab and 9.9% for standard therapy See notes for abbreviations

11 Objective Response Rate Nivolumab (n=240) Standard Therapy (n=121) Objective response rate, n (%) 32 (13.3) 7 (5.8) 95% CI 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 ( ) 2.0 ( ) See notes for reference and abbreviations

12 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 Standard Therapy Responders Weeks 100 Stable Disease Weeks 100 Stable Disease Weeks 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

13 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 ( ) Nivolumab ( ) 100 Standard Therapy ( ) 100 Standard Therapy ( ) Hazard ratio for death, 0.55 (95% CI, ) 90 Hazard ratio for death, 0.89 (95% CI, ) Nivolumab 30 Nivolumab No. at Risk Nivolumab Standard Therapy 10 0 Standard Therapy Months Standard Therapy Months Estimates for OS HR for PD-L1 expression levels of 5% and 10% are similar to those for 1% See notes for abbreviations

14 Mean Change From Baseline (95% CI) Worse Better QoL: EORTC QLQ-H&N35 Symptom Burden Pain Sensory Problems Social Contact Problems 10 MID P < P = P = P < P = P = MID Week Nivolumab Investigator's 15 choice

15 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

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) 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 (12.6) 3 (2.7) Neutropenia (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

23 FUTURO

24 FUTURO 1ª Línea: DURVALUMAB +/- TREMELIMUMAB PEMBROLIZUMAB +/- PLATINO NIVOLUMAB + IPILIMUMAB PEMBRO/NIVO + EPACADOSTAT 2ªLínea: DURVALUMAB +/- TREMELIMUMAB DURVALUMAB +/- AZD9150 ATEZOLIZUMAB QTRT: CISPLATINO + PEMBROLIZUMAB CETUXIMAB + DURVALUMAB INDUCCIÓN

25 CASO CLÍNICO 3ª LÍNEA (9s) NIVOLUMAB

26 NIVOLUMAB: 3mg/kg peso basal EVOLUCIÓN: EFICACIA Y CALIDAD DE VIDA RESPUESTA PARCIAL MANTENIDA a todos los niveles 2 años

27 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

28 GRACIAS!

Immune Checkpoint Inhibitors for Lung Cancer William N. William Jr.

Immune Checkpoint Inhibitors for Lung Cancer William N. William Jr. Diretor de Onco-Hematologia Hospital BP, A Beneficência Portuguesa Non-Small Cell Lung Cancer PD-1/PD-L1 Inhibitors in second-line therapy