Resultados de sobrevida a largo plazo en CheckMate 057 y CheckMate 017 Mariano Provencio Servicio Oncología Médica Hospital Universitario Puerta de Hierro, Madrid

De un tiempo a esta parte…. SLIDE INTERIOR PRESENTACIÓN ¿De dónde venimos?

La supervivencia global en cáncer de pulmón…. The impact of second-line therapy on survival. Inmunoterapia Soria J C et al. Ann Oncol 2010;21:2324-2332

La definición de largo superviviente era (una excepción) para aquellos que vivían más de 2 años y rara vez más de 5 años en aquellos con posibilidad de resección de metástasis Damme VV et al. Lung Cancer 2013

¿La inmunoterapia da resultados a largo plazo? Nivolumab: long follow up Trials CheckMate 003: DATOS A 3 Y 5 AÑOS CONSOLIDADOS CheckMate 017: DATOS A 3 y 4 AÑOS CONSOLIDADOS CheckMate 057: DATOS A 3 y 4 AÑOS CONSOLIDADOS

Anti-PD-1 demonstrates encouraging survival in pre-treated patients: nivolumab as an example CA209-003: phase 1 follow-up study, up to 5 prior lines of therapy, stage IIIB/IV squamous and non-squamous (NSCLC cohort Pts at Risk Group Died/Treated Median OS, mo (95% CI) 1-year 2-year 3-year 9.2 (5.3, 11.1) 14.9 (7.3, 30.3) 9.2 (5.2, 12.4) Months Since Initiation of Treatment 100 90 80 70 60 50 40 30 20 10 3 6 9 12 15 18 33 27 24 21 36 39 42 45 48 51 54 66 63 57 Censored 3-year OS = 27% 2-year OS = 42% Nivolumab 1 mg/kg Nivolumab 3 mg/kg Nivolumab 10 mg/kg OS (%) 33 (17, 49) 56 (38, 71) 38 (26, 50) 15 (5, 30) 42 (24, 58) 20 (11, 31) 27 (12, 43) 14 (7, 25) 26/33 23/37 50/59 1 mg/kg 3 mg/kg 10 mg/kg 37 59 26 34 35 16 29 17 22 7 14 13 4 11 1 5 2 OS rate, % (95% CI) 70% of patients had 3–5 prior lines of therapy; 46% of these patients had received 12 prior lines of therapy and 54% had received 35 prior lines of therapy. Brahmer J, et al. Poster presented at ASCO 2014 (Abstract 8112).

AARC 2017

Brahmer J et al. Presented at AACR Annual meeting 2017 Brahmer J et al. Presented at AACR Annual meeting 2017. Abstract #: CT077. Oral presentation

Hazard Ratio 0.59% CI: 0.44, 0.79, p=0.00025] 9.2 months 6 months Nivolumab Docetaxel Median OS- 9.2 months 6 months

Kaplan–Meier Estimates of OS (2 Years Minimum Follow-up) ASCO 2016

Kaplan–Meier Estimates of OS (2 Years Minimum Follow-up) ASCO 2016

ESMO MADRID 2017

OS (4 years’ minimum follow-up) CheckMate 017 (SQ NSCLC) CheckMate 057 (non-SQ NSCLC) CI = confidence interval; HR = hazard ratio; NSCLC = non-small cell lung cancer; OS = overall survival;; SQ = squamous.. OS data are based on a May 2018 database lock (minimum of 4 years of follow-up). Median follow-up was not reported. PFS, ORR, and DOR data are based on a June 22, 2017, database lock (minimum of 40.3 months follow-up for survival). Median follow-up was not reported. a Investigator-assessed. bAmong responders (n = 27, n = 12 in the nivolumab and docetaxel groups, respectively).  1. Data on file. NIVO 415. Princeton, NJ: Bristol-Myers Squibb.

¡¡ CALIDAD DE LA RESPUESTA !! ESMO MADRID 2017

Seguridad a largo plazo

LCSS Symptom Burden Index Change From Baseline Worse 1.0 0.9 0.8 0.7 0.6 0.5 0.4 12 24 30 36 42 48 54 60 40 20 10 -10 -20 -30 -40 Nivolumab Population Norm* Docetaxel Lung Cancer Norm (UK-based): 0.67† Mean EQ-5D Utility Index Score LCSS Symptom Burden Index Change From Baseline Better Docetaxel Nivolumab 12 24 30 36 42 48 54 60 EQ-5D=European Quality of Life-5 Dimensions; I-O=immuno-oncology; LCSS=Lung Cancer Symptom Scale; MID=minimally important difference; PRO=patient-reported outcome; SD=standard deviation. Time (weeks) Time (weeks) EQ-5D Utility Index Mean Scores Over Time While On Treatment* LCSS Symptom Burden Index (On-Treatment)†

Influencia de los biomarcadores largo plazo

2-year OS Rates Overall and by PD-L1 Expression Level in CheckMate 057 (non-SQ NSCLC) Se podría agregar la información a 3 años? aKaplan–Meier estimates, with error bars indicating 95% Cls bFor the comparison of the full Kaplan–Meier survival curves for each treatment group

ESMO MADRID 2017

Among patients with PD-L1 not evaluable/unknown: CheckMate:057 Efficacy: OS by PD-L1 Expression: 4-Year Minimum Follow-up 1% PD-L1 5% PD-L1 10% PD-L1 Among patients with PD-L1 not evaluable/unknown: mOS (95% CI) for nivolumab (n = 61) was 9.20 (5.91, 12.75) mo mOS (95% CI) for docetaxel (n = 66) was 10.48 (7.20, 13.90) mo HR (95% CI) for the comparison of nivolumab to docetaxel was 0.89 (0.62, 1.28) CI = confidence interval; HR = hazard ratio; mo = months; NSCLC = non-small cell lung cancer; NSQ = nonsquamous; OS = overall survival; PD-L1 = programmed death-ligand 1. Data based on a May 2018 database lock (minimum of 4 years of follow-up). Median follow-up not reported. Symbols represent censored observations. Data on file. NIVO 416. Princeton, NJ: Bristol-Myers Squibb.

CheckMate:057 Efficacy: OS by PD-L1 Expression: 4-Year Minimum Follow-up AARC 2017

Conclusiones La inmunoterapia: sí ha cambiado la supervivencia Hace sólo unos años la supervivencia a más de 2 años era la excepción Nivolumab en segunda línea Supervivencia global a 3 años del 17% Supervivencia libre de progresión del 10% Calidad de la duración de la respuesta No empeora la toxicidad Mejora la calidad de vida Se mantiene el beneficio de acuerdo a la determinación de PDL1 Todos los estudios tienen puntos de crítica porque ningún ensayo puede responder todas las dudas a la vez El futuro es imposible verlo sin la inmunoterapia