- The document discusses pancreatic cancer epidemiology and molecular biology. Some key points: - Worldwide, pancreatic cancer incidence is about 8 per 100,000 and mortality is 7-8 per 100,000, making it the 8th most common cancer. - In Chile, incidence and mortality are slightly higher than worldwide averages. - About 60% of pancreatic cancers are metastatic at diagnosis, 30% are locally advanced, and only 10% are early-stage. - KRAS mutations are present in approximately 95% of pancreatic cancers.

1. Cáncer Páncreas
Epidemiología
Biología Molecular
Dr. Daniel Agüero V
Residente Oncología Médica
Septiembre 2017

2. Mundial
 Incidencia: 8 x 100.000
 Mortalidad: 7-8 x 100.000
 Ocupa 8º Lugar en
Frecuencia
Globocan 2012, OMS

3. Mundial
 Hombres:
- I: 4.9 x 100.000
- M: 4.5 x 100.000
 Mujeres:
- I: 3.6 x 100.000
- M: 3.5 x 100.000
Globocan 2012, OMS

4. © International Agency for Research on Cancer 2016
INCIDENCIA
Chile 4.8
http://globocan.iarc.fr/Pages/Map.aspx

5. © International Agency for Research on Cancer 2016
MORTALIDAD
Chile 5.2

6. Hombres
Chile 4.9 Chile 5.3
Incidencia Mortalidad

7. Mujeres
Incidencia Mortalidad
Chile 4.6 Chile 5.0

8. Hombres:
- Incidencia: 5.7 x 100.000
VALDIVIA
Primer informe de registros poblacionales de cáncer de Chile,
Quinquenio 2003-2007. Minsal Publicado 2012

9. Mujeres:
- Incidencia: 5.4 x 100.000
VALDIVIA
Primer informe de registros poblacionales de cáncer de Chile,
Quinquenio 2003-2007. Minsal Publicado 2012

10. Mortalidad Valdiva
Primer informe de registros poblacionales de cáncer de Chile,
Quinquenio 2003-2007. Minsal Publicado 2012

11. USA
Cancerstatisticscenter.cancer.org
ACS 2017

12. Cancerstatisticscenter.cancer.org
ACS 2017

13. Otros Datos:
 71 a Promedio Dg
 74% entre 55 y 84 años
 12% < 55 años
 14% > 84 años
 H:M 1.3:1
 Mayor en Afroamericanos.
 Riesgo de Desarrollar Ca.Páncreas 1.5% (1/65)

17. Cáncer de páncreas
60% -
Metastásico
30% - Localmente
avanzado
10% - Temprano
Distribución por estadío
Temprano
Localmente
avanzado
Metastásico
• 15-19 meses
• 9-12 meses
• 3-6 meses
Mediana Sobrevida

18. Estroma:

19. - Fibroblastos asociados a Cáncer (predominantemente)
- Células Inmunes.
- Matriz Extracelular
Von Ahrens et al. Journal of Hematology & Oncology (2017)

20. Nielsen MFB et al . Tumour-stroma interaction in pancreatic cancer

21. Gnatenko et al, Biochemistry (Moskow) 2017

22. Ansari et al, SJOG, 2017
Cross Talk

23. KRAS

24. Zeitouni et al, Cancers 2016
Aprox 95%

27. Tratamiento Cáncer de Páncreas
Dr. Daniel Agüero V
Residente Oncología Médica
Septiembre 2017

28. Quimiorradioter
apia adyuvante
con FU (GITSG,
1985)
Gemcitabina
mejor que FU en
enfermedad
metastásica
(Burris, et al.)
FOLFOXIRI
mejor que
Gemcitabina en
enfermedad
metastásica
(PRODIGE)
Radioterapia
adyuvante
supérflua –
(ESPAC)
Cáncer de páncreas: Evolución del tratamiento
Adyuvancia / Metastásico
1985 1997 2004 2010
Quimioterapia
adyuvante mejor
que
Observación –
(CONKO-01)
Gemcitabina
adyuvante menos
tóxica que FU –
(ESPAC 3)
Gemcitabina +
Capecitabina
adyuvante mejor
que Gemcitabina
sola– (ESPAC 4)
2017

29. Adyuvancia:

30. Trial Therapy N Med Surv 2 Yr
Surv
5 Yr
Surv
GITSG FU+RT+FU 21 20m 43% 18%
Observation 22 11m 18% 5%
EORTC 40891 FU+RT 60 17.1m 37% 20%
Observation 54 12.6m 26% 10%

31. CONKO 001
 Estratificado por: Endpoint Primario:
– R0 vs R1 - Sobrevida Libre de Enfermedad
– T1/2 vsT3/4 Endpoint Secundario:
– N+ vs N - - Toxicidad, Calidad de vida, SG
Adenocarcinoma
Pancreas Qx
R0 o R1
(N = 368)
Gemcitabina
1000mg/m2 d1,8,15 c/28d x 6
(n = 179)
Observación
(n = 175)
Oettle et al JAMA 297:267-277, 2007
®

32. Oettle et al JAMA 297:267-277, 2007
CONKO-001 Trial
Med DFS 13.4 m Gem
6.9 m Obs
OS 3/5 yr 34/22.5% Gem
20.5/11.5% Obs

33. Med Sob. 13.1 m Gem
7.3 m Obs
Med Sob. 15.8 m Gem
5.5 m Obs
Oettle et al JAMA 297:267-277, 2007
CONKO-001 Trial
R0 vs R1

34. CONKO-001
DFS

35. CONKO-001
OS

36. Gemcitabine Observation P-value
Median DFS 13.4m 6.9m HR: 0.55 CI 0.44-0.69 P= <0.001
Median OS 22.8m 20.2m HR: 0.76 CI 0.61-0.95 P= 0.01
5 year OS 20.7% 10.4%
10 year OS 12.2% 7.7%
CONKO-001 Efficacy Results
Median Follow up: 11 years
Oettle et al JAMA 2007 Oettle et al JAMA 2013

37. Neoptolemos et al, Lancet 2001

38. CRT No CRT P-value
All 175 178
Median OS 15.5m 16.1m 0.24
2 x 2 design 145 144
Median OS 15.8m 17.8m 0.09
CT No CT P-value
All 238 235
Median OS 19.7m 14m 0.005
2 x 2 design 147 142
Median OS 17.4m 15.9m 0.19
Neoptolemos et al, Lancet 2001
ESPAC 1 Results:

39. - Este estudio no mostró beneficio CRT
adyuvante, pero sí reveló beneficio potencial
quimioterapia adyuvante.
- Peor Pronóstico:
- Márgenes ( + )
- Compromiso LN
Neoptolemos et al, Lancet 2001
ESPAC 1 Conclusiones:

40. After
potentially
curative
resection
(N = 289)
Observation
(n = 69)
Chemoradiotherapy
same as GISTG 20 Gy to tumor over 2 weeks plus
5-FU 500 mg/m2 on Days 1-3 of radiotherapy x 2 cycles
(n = 73)
Chemotherapy
Leucovorin 20 mg/m2 plus 5-FU 425 mg/m2,
Days 1-5 of 28 x 6 cycles
(MAYO) (n = 75)
Combination Chemoradiotherapy
Chemoradiotherapy followed by chemotherapy,
administered as above
(n = 72)
Neoptolemos JP, et al. NEJM. 2004;350:1200-1210.
4-arm study
ESPAC 1 Trial:

41.  Median Survival
 CTR vs No CTR:
– 2-year survival: 28.5% vs 41.4%
– 5-year survival: 10% vs 20%
 QMT vs No QMT :
– 2-year survival: 40% vs 30%
– 5-year survival: 21% vs 8%
ESPAC 1 : CRT Resultados fueron
peores!
Neoptolemos JP, et al. NEJM. 2004;350:1200-1210.

42. Median Survival
No chemoradiotherapy: 17.9 months
Chemoradiotherapy: 15.9 months
HR: 1.28 (95% CI: 0.99-.66); P = .05
0
100
75
50
25
0
12 24 36 48 60 72
Months
Survival,%
Chemoradiotherapy
No chemoradiotherapy
ESPAC 1 Trial:
Neoptolemos JP, et al. NEJM. 2004;350:1200-1210.

43. 0
100%
75%
50%
25%
0%
12 24 36 48 60 72
Chemotherapy
No chemotherapy
Months
Survival(%)
ESPAC 1 Trial:
Median Survival
Chemotherapy: 20.1 months
No Chemotherapy: 15.5 months
HR: 0.71 (95% CI: 0.55-0.92); P = .009
Neoptolemos JP, et al. NEJM. 2004;350:1200-1210.

44. Críticas ESPAC 1 :
 Sólo 128 ptes tenían detalles de los campos irradiados y de éstos 90
recibieron dosis completa.
 No se irradió a 19 pctes por Progresión.
 La Radiación fue subóptima.
 Los médicos y los pacientes evitaban la randomización original y
seleccionaban directamente los brazos.
 Pacientes en los brazos de observación podrian haber recibido
quimioterapia y/o radioterapia, violando el protocolo.

45. Conclusiones
 La quimioterapia de mantenimiento incrementa la supervivencia
en pacientes con cáncer de páncreas resecado
 Sin embargo, la combinación de quimioterapia con radioterapia
puede disminuir la supervivencia
 El estándar de tratamiento en pacientes con cáncer de
páncreas resecable debe incluir quimioterapia adyuvante
Neoptolemos, et al. N Engl J Med. 2004;350:1200-1210.

46. ESPAC 3: Gemcitabina vs FU
adyuvante
Neoptolemos JP, et al. JAMA 310(10); 1073, 2010
Pacientes con cáncer
de páncreas
resecado
(n = 1088)
Gemcitabina x6 meses*
FULV x6 meses*
*Gemcitabina: 1000 mg/m2 IV cada semana x3, se repite ciclo cada 4 semanas, por 6 ciclos.
FULV: Leucovorina 20 mg/m2/día seguido por FU (Fluoruracilo) 425 mg/m2/día en bolo x5 días, cada 4 semanas, por 6 ciclos
 No diferencia en Sobrevida al analizar todos los grupos
– mSobrevida: 23 meses en ambos grupos
 Gemcitabina con menores eventos adversos serios (7.5% vs 14%), p=0.01

47. ESPAC 3:
Sin Diferencia
Toxicidad: 5FU/LV Gemcitabina P
G 3 – 4 14% 7.5% <0.001
Tromobocitopenia 0% 1.5% 0.0034
Mucositis 10% 0% <0.001
Diarrea 13% 2% <0.001
Neoptolemos JP, et al. JAMA 310(10); 1073, 2010
Gemcitabine: 23.6m
FULV: 23m
HR: 0.94 (CI:0.81-1.08)
p= 0.39

48. RTOG 9704: Quimiorradioterapia con
FU + (Gemcitabina vs FU adyuvante)
Pacientes con cáncer
de páncreas
T1-T4 N0-N1 MO)
(N = 442)
FU x1 mes, seguido por XRT+FU,
seguido por FU x 3meses*
Gemcitabina x1 mes,
seguido por XRT+FU, seguido por
Gemcitabina x 3 meses
*Gemcitabina: 1000 mg/m2 IV cada semana x3 (antes de RT), y por 12 semanas (después de RT)
FU (Fluoruracilo) 250 mg/m2/día en infusión continua por 3 semanas (antes de RT) y por 3 meses (después de RT)
XRT: 50.4 Gy + FU 250 mg/m2/día en infusión continua durante la radioterapia
 No diferencia en Sobrevida al analizar todos los grupos
– Sin embargo, los pacientes con tumores de la cabeza de páncreas mostraron
incremento de la supervivencia a favor de gemcitabina
– SG: 16.9m vs 20.6 m
– Sobrevida a 3 años: 31% vs 21%
Regine et al, JAMA 2008

49. Tumores de Cabeza de Páncreas
N: 381 Gemcitabina 5 FU
Mediana SG 20.6 m 16.9 m
3 a SG 32% 21%
p=0.03
- Tendencia Sobrevida para Gemcitabina
- Desequilibrio en T3 – T4, Brazo Gem 81% vs FU 70%
- Cuando en Analisis se incluye Tu. Cuerpo/Cola (n: 442) no hubo
diferencia significativa (p=0.15)
Regine et al, JAMA 2008
RTOG 9704 Trial

50. %ALIVE
0
25
50
75
100
YEARS FROM RANDOMIZATION
0 1 2 3 4
/ // /
/
/
/
/
/
/
/
/ / // / /////// //// / / / ///// ///// / /////// // //
RTOG 9704 / US INTERGROUP
Phase III Adjuvant Study Overall Survival – ‘Pancreatic Head’ Patients Only
134
132
77
63
46
31
24
19
187
194
Patients at Risk
RT + GEM
RT + 5FU
Total Dead MST
CRT + Gemcitabine 187 134 1.72
CRT+ 5-FU 194 156 1.41
p = 0.033
Median: 20.6 vs 16.9mos
3-Year: 32% vs 21%
Regine et al, JAMA 2008

51. Regine et al, JAMA 2008

52. Site All pacients
n=197
Pancreatic Head
N=173
All pacients
n= 184
Pancreatic Head
N=155
Local 55 (28) 49 (28) 43 (23) 35 (23)
Regional 15 (8) 14 (8) 13 (7) 13 (8)
Distancia 140 (71) 123 (71) 138 (75) 119 (77)
Chemoradiation + 5 FU Chemoradiation + Gemcitabine
Nº ( % ) of Patients With Relapses
RTOG 9704 Trial
Regine et al, JAMA 2008

53. %ALIVE
0
25
50
75
100
YEARS FROM RANDOMIZATION
0 1 2 3 4 5
CA19-9 < 180
Lewis Antigen Negative
CA19-9 ≥ 180
164
94
10
93
46
3
56
29
0
39
21
0
Lewis Antigen Negative p = 0.25
CA19-9 ≥ 180 p = < 0.0001
Patients at Risk
CA19-9 < 180
Lewis Antigen Neg.
CA19-9 ≥ 180
220
132
33
22
10
0
Survival Curve for all patients by CA 19-9 grouping

54. SUMMARY
 A post-resection CA 19-9 level ≤ 180 U/ml corresponds to a 72% reduction in death
in all patients treated with adjuvant chemoradiation for pancreatic cancer compared
to patients with CA 19-9 > 180 U/ml.
 This is independent of treatment, margin status, size of primary tumor, and nodal
involvement.
 Post-resection CA 19-9 was a prognostic factor in all patient groups (all, head only,
non-head lesions) with HR of 3.58, 3.52, and 4.61, respectively.
 The incidence of Lewis Antigen negative patients (34%) may be higher than
previously thought; these patients have survival which is comparable to patients with
CA 19-9 levels ≤180 U/ml.

55. CONCLUSIONS
 Post-resection CA 19-9 is an important
prognostic factor in patients undergoing
adjuvant chemoradiation for pancreatic
adenocarcinoma.
 Patients with post-resection CA 19-9 levels
>180 U/ml have a very poor survival (median=9
months).
 These patients should be considered for
additional/prolonged chemotherapy.

56. JASPAC 01:
Randomized phase III trial
Fukutomi et al. J Clin Oncol 2013
R
1:1
Stratification
• Institution, residual tumour status
(R0 / R1), nodal status (N0 / N1)
Patients with resected
pancreatic cancer
• ECOG PS 0–1
• Adequate organ
function
(n=385)
Gemcitabine 1000 mg/m2 iv d1, 8, 15
q4w for 6 courses
S-1 80 / 100 / 120 mg/d based on BSA,
po, d1–28, q6w for 4 courses
Primary endpoint
• OS
Secondary endpoints
• RFS, adverse events, QoL (EQ-5D)

57. JASPAC 01 Overall Survival
Primary Endpoint
0
50
100
0 1 2 3 4 5 years
(%) P<0.0001 for non-inferiority
P<0.0001 for superiority
70%
53%
S-1
GEM

58. JASPAC 01 Trial
– Una gran Proporción de pctes en el brazo Gemcitabina descontinuaron
el Tratamiento (42%) más que el Grupo S-1 (28%)
– Alta incidencia de Leucopenia Grado 3 – 4 con Gemcitabina (39%) vs
S-1 (9%)
– QoL (EQ-5D) scores fueron mayores en S1
Outcome
S-1
% (95% CI)
Gemcitabine
% (95% CI) HR (95% CI) p-value
OS 70 (63, 76) 53 (46, 60) 0.54 (0.35, 0.83)* <0.0001 for non-inferiority
<0.0001 for superiority
RFS 49 (42, 56) 29 (23, 35) 0.57 (0.45, 0.72) <0.0001 for superiority
 Puntos Claves:
– 378 pctes (G/S: 191/187) includos en el Analisis Final
 Fukutomi et al. J Clin Oncol 2013

59. Conclusiones:
– En pacientes con Ca. Páncreas Resecado, Adyuvancia S-1 fue bien
tolerada y superior a Gemcitabina en SG y SLR.
– S-1 es considerada el nuevo estandard de tratamiento en Ca.
Páncreas resecado en Asia.
 Fukutomi et al. J Clin Oncol 2013

60. Gemcitabine vs. Fluoropyrimidine
(FP): Phase III Adjuvant Studies
CONKO-
001
RTOG 97-04 ESPAC-3 JASPAC 01 ESPAC-4
GEM v Obs GEM v inf-FU
+ C-RT
GEM v b-FU GEM v S-1 GEM+Cap
e v GEM
mD
FS
mon
G
E
M
13.4 11.4 14.3 11.2
F
P
6.9 10.1 14.1 23.2
mO
S
mon
G
E
M
22.8 20.5 23.6 25.5 25.5
F
P
20.2 16.9 23 46.3 28

61. CONKO-001 RTOG 97-04 ESPAC-3 JASPAC 01
GEM v Obs GEM v inf-FU
+ C-RT
GEM v b-FU GEM v S-1
Node positive, % 72 67 72 63
R0, % 81 66 65 87

62. ESPAC-4:
Multicenter, International, Open-Label Randomized Controlled Phase III Trial
*1000 mg/m2 d1,8,16 (6 cycles); †1660 mg/m2 21/28d.
Neoptolemos et al. J Clin Oncol 2016; 34 (suppl): abstr
LBA4006
R
1:1
PD
Gemcitabine* +
Capecitabine†
(n=364)
Key patient inclusion criteria
• Pancreatic ductal ADC
• R0 or R1 resection
• No ascites, liver or
peritoneal metastases
• WHO PS ≤2
• No malignancy diagnoses
(n=730)
PRIMARY ENDPOINT(S)
• OS
SECONDARY ENDPOINTS
• Safety
PD
Gemcitabine* alone
(n=366)

63. *Stratified by resection margin status and country.
CAP, capecitabine; GEM, gemcitabine. Neoptolemos et al. J Clin Oncol 2016
Gemcitabine + Capecitabine (n=366) Gemcitabine (n=364)
5-year OS, % (95% CI) 28.8 (22.9, 35.2) 16.3 (10.2, 23.7)
χ2; p-value* 4.61; 0.032
0
0
OS by treatment armOS(%)
GEM+CAP mOS: 28.0 months (95% CI 23.5, 31.5)
GEM mOS: 25.5 months (95% CI 22.7, 27.9)
HR 0.82 (95% CI 0.68, 0.98)
x
2
=4.61; p=0.032
Months
100
90
80
70
60
50
40
30
20
10
10 20 30 40 50 60
ESPAC-4:

64. LN, lymph nodes; N/A, not available; RM, resection
margin. Neoptolemos et al. J Clin Oncol 2016; 34 (suppl): abstr LBA4006
OS by disease grade OS by disease stage
OS by lymph nodes OS by resection margin
OS(%)
I
II
III
IV
x2=12.71; p=0.005
Months
mOS: N/A
mOS: 39.3 (95% CI 18.1, 49.2)
mOS: 26.0 (95% CI 23.5, 28.0)
mOS: 15.7 (95% CI 4.8, N/A)
0 20 30 40 50 6010
0
10
20
30
40
50
60
70
80
90
100
OS(%)
Negative LN
Positive LN
Months
x2=38.66; p<0.001
mOS: 58.6 (95% CI 43.5, 64.3)
mOS: 23.3 (95% CI 22.0, 26.0)
0 20 30 40 50 6010
0
10
20
30
40
50
60
70
80
90
100
OS(%)
Negative RM
Positive RM
x2=17.65; p<0.001
mOS: 34.6 (95% CI 28.0, 41.0)
mOS: 23.3 (95% CI 21.9, 26.2)
Months
0 20 30 40 50 6010
0
10
20
30
40
50
60
70
80
90
100
OS(%)
Well
Moderate
Poor
x2=38.21; p<0.001
mOS: 41.1 (95% CI 30.9, 59.8)
mOS: 30.7 (95% CI 26.2, 36.9)
mOS: 19.0 (95% CI 16.6, 22.0)
0 20 30 40 50 6010
0
10
20
30
40
50
60
70
80
90
100
Months
ESPAC-4:

65. CAP, capecitabine; GEM, gemcitabine;
RM, resection margin.
Neoptolemos et al. J Clin Oncol 2016; 34 (suppl): abstr
LBA4006
OS by treatment arm and resection margin
OS(%)
x2=23.44; p<0.001
Months
mOS: 23.0 (95% CI 21.6, 26.2)
mOS: 27.9 (95% CI 23.8, 34.6)
mOS: 23.7 (95% CI 20.7, 27.1)
mOS: 39.5 (95% CI 32.0, 58.0)
0 20 30 40 50 6010
0
10
20
30
40
50
60
70
80
90
100
GEM, Positive RM
GEM, Negative RM
GEM-CAP, Positive RM
GEM-CAP, Negative RM
ESPAC-4:

66. *Exploratory analysis: Fisher's exact test.
 Treatment related SAEs: 24% gemcitabine + capecitabine vs 26% gemcitabine alone
Neoptolemos et al. J Clin Oncol 2016
AEs Grade 3–4 in ≥5%
of patients, n (%)
Gemcitabine + Capecitabine
(n=359)
Gemcitabine
(n=366)
p-value*
Diarrhoea 19 (5) 6 (2) 0.008
Fatigue 20 (6) 19 (5) 0.870
Infection/infestation 9 (3) 24 (7) 0.012
Neutrophils 137 (38) 89 (24) <0.001
Hand-foot syndrome 26 (7) 0 <0.001
WBC 37 (10) 28 (8) 0.242
ESPAC-4:

67. Conclusiones:
 Gemcitabina + Capecitabina Adyuvante demostró un aumento
significativo en SG vs Gemcitabina sola en paciente con Cáncer de
Páncreas Resecado.
 Las toxicidades fueron ligeramente más frecuentes con la
combinación vs monoterapia, pero en general estas fueron
manejables
 La Tasa de SG 5 años fue superior a los ESPAC previos
 Quimioterapia Adyuvante con Gemcitabina + Capecitabina es el
nuevo SoC en este setting.
Neoptolemos et al. J Clin Oncol 2016

68. Metastásico:

69. Burris: Gemcitabina vs FU en Cáncer
de Páncreas Metastásico
Referencia: Burris HA, et al. JCO 15; 2403, 1997
Cáncer de páncreas
avanzado,
sintomático
(n = 126)
Gemcitabina*
n=63
FULV*
n= 63
*Gemcitabina: 1000 mg/m2 IV cada semana x7, seguido por 1 semana de descanso. Seguido por Gemcitabina semanal x3, de cada 4 semanas
FULV: Folinato de calcio 20 mg/m2/día seguido por FU (Fluoruracilo) 425 mg/m2/día en bolo x5 días, cada 4 semanas, hasta progresión
 Endpoint 1º: Beneficio Clínico (índice compuesto por control del dolor, Karnofsky PS y
peso). Se requiere de la mejoría de 1 parámetro por más de 1 mes, sin el deterioro de
otros.
– Tasa de Respuesta
– Sobrevida Global y al Año

70. Cáncer Páncreas Metastásico:
Gemcitabina como Tto de Elección:
 Mediana SG:
5.65 vs 4.41 m (P = .0025)
 1º año SG:
18% vs 2%
 Beneficio Clínico:
23.8% vs 4.8% (P = .0022)
 Tasa Respuesta :
5.4% vs 0% (P = NS)
Burris HA, et al. J Clin Oncol. 1997;15:2403-2413.
Gemcitabine
5-FU
100
80
60
40
20
0
0 2 4 6 8 10 12 14 16 18 20
Mos
PtsSurviving(%)

71. ECOG E2297:
Randomized phase III trial
Berlin et al. J Clin Oncol 2002
R
Estratification
• PS y Enfermedad Primaria
Paciente cancer
pancreas confirmado
por histologia e
irresecable.
ECOG PS 0–2
Buen estado funcional
(n=322)
Gemcitabina 1000mg /m2 semanal +
5 FU 600mg /m2 + LV 25mg /m2
cada 3 o 4s
n= 160
Gemcitabina 1000mg /m2 semanal
cada 3 o 4s
n= 162
Primary endpoint
• SG
Endpoints Secundarios
• Tasa Respuesta, Tiempo a la Progresion

72. Resultados:
Gem + FU Gem + FU
Gem sola
Gem sola
3.4m vs 2.2 m
p= 0.022
6.7m vs 5.4m
p= 0.09
SG SLP
No estadisticamente significativo

73. Randomizados Gem + 5FU:
Autor Tratamiento TTP (m) SG (m)
Di Costanzo
(2005) (FII)
Gemzar 1000mg/m2/sem
G + 5-FU 200mg/m2/d IC
3.2
4.2
7.2
6.9
Berlin
(2002)
Gemzar 1000 mg/m2/sem
G+ 5-FU 600 mg/m2 b
2.2
3.4*
5.6
6.9
Riess
(2005)
Gemzar 1000 mg/m2/sem
G+ 5-FU 750mg/m2ic/sem
+ LV 200mg/m2
3.5
3.5
5.8
6.2

74. Randomizados Gem + Capecitabina
Autor Tratamiento TTP (m) SG (m)
Scheithauer
(2003) (FII)
Gemzar 2200mg/m2/ 2 sem
G + XEL 2500mg/m2 D1-7
4.0
5.1
8.2
9.5
Cunningham
(2005)
Gemzar 1000 mg/m2/sem
G+ XEL 1660 mg/m2 D1-21
-
-
6.2
7.1
Herrmann
(2005)
Gemzar 1000 mg/m2 D1-8
G+ XEL 1300mg/m2 D1-14
4.0
4.8
7.3
8.4

75. Sobrevida Global GEM CAP
Median survival 12-month
(months, 95%CI) survival
GEM 6.2 22%
GEM-CAP 7.1 24%
Hazard Ratio:
0.86 (95% CI: 0.72, 1.02)
Log rank p=0.08
Cunningham et al, JCO 2009

76. Estudios Fase III: Gem/Platinos
Estudio Tratamiento Mediana SLP, m Mediana SG, m
Gruppo Oncologia
dell‘Italia Meridionale
Study (N = 107)
Gemcitabine 2.0 5.0
Gem/cisplatin 5.0 (P = .048) 7.5 (P = .48)
German Multicentre
Study (N = 190)
Gemcitabine 3.1 6.0
Gem/cisplatin 5.3 (P = .053) 7.5 (P = .15)
GERCOR/GISCAD
Study (N = 313)
Gemcitabine 3.7 7.1
Gem/oxaliplatin 5.8 (P = .04) 9.0 (P =.13)
ECOG 6201 (N = 833)
*Third arm = FDR gem
Gemcitabine N/A 4.9
Gem/oxaliplatin N/A 5.9
Viret, et al (N = 83)
Gemcitabine 2.5 6.7
Gem/cisplatin 2.2 (P = NS) 8.0 (P =.73)
Analisis Combinado: gemcitabina/platinos resulta en
Aumento significativo SG (HR: 0.85; P = .01).

77. Ciliberto et al, European Journal of Cancer 2013

78. PA.3: Erlotinib Becomes First
Targeted Agent Approved for
Pancreatic Cancer Use

79.  Center
 ECOG PS (0 or 1 vs 2)
 Stage of disease
(locally advanced vs
distant metastases)
(N = 569)
R
A
N
D
O
M
I
Z
E
D
Gemcitabine 1000 mg/m2 IV
+
Erlotinib 100 mg/day PO
(n = 285)
or
Erlotinib 150 mg/day PO
(n = 48)
Gemcitabine 1000 mg/m2 IV
+ Placebo
(n = 284)
Stratified by
EGFR status was not an eligibility requirement
PA.3 Trial: Study Schema
Moore MJ, et al. J Clin Oncol. 2007;25:1960-1966.

80. PA.3: Survival Results
Moore MJ, et al. J Clin Oncol. 2007;25:1960-1966.
100
80
60
40
20
0
0 6 12 18 24
Months
SurvivalProbability(%)
Placebo (n = 284)
Median: 5.91 mos
1-yr survival: 17%
Erlotinib (n = 285)
Median: 6.24 mos
1-yr survival: 23%
HR: 0.82 (95% CI: 0.69-0.99;
P = .038)

81. PA.3: OS relative to grade of rash
p<0.0001 HR (rash)=0.71
Grade 0
Grade 1
Grade 2
1.0
0.8
0.6
0.4
0.2
0
Survivalprobability
0 5 10 15 20
Time (months)
Grade 0
(n=79)
Grade 1
(n=108)
Grade 2
(n=103)
Median OS (months) 5.29 5.75 10.51
1-year survival (%) 16 11 43
Moore M, et al. J Clin Oncol 2007;25:1960–6; Roche, data on file

82. PA.3: Toxicities Associated With
Erlotinib
Toxicities, All Grades/
Grade 3 or 4, %
Gemcitabine + Erlotinib
(n = 282)
Gemcitabine + Placebo
(n = 280)
Diarrhea 56/6 41/2
Fatigue 89/15 86/15
ILD-like syndrome* 2.1 0.4
Rash 72/6 29/1
Stomatitis 23/<1 14/0
Moore MJ, et al. J Clin Oncol. 2007;25:1960-1966.
*Pneumonitis, pulmonary infiltrate

83. Locally advanced/metastatic
pancreatic cancer: CALGB 80303
Locally advanced
or metastatic
Pancreatic Ca
N=602
R
Gemcitabine 1000mg/m2 d1 8 15
q28d Placebo
Gemcitabine 1000mg/m2 d1 8 15
q28d Bevacizumab 10mg/kg d1
d15 q28d
Primary endpoint:
•Overall survival
Secondary endpoints:
• objective response rate, duration of
response, progression-free survival, toxicity
Kindler et al JCO 2010
Trial closed by DSMB as crossed futility boundary

84. Locally advanced/metastatic pancreatic
cancer CALGB 80303
Gemcitabine
Placebo
Gemcitabine
Bevacizumab
CR (%) 2 1
PR (%) 8 10
SD (%) 31 36
Disease control
rate (%)
40 47
Median OS
(months)
6.1 5.8 P=0.78
PFS (months) 4.7 4.9 P=0.99
1yr OS (%) 20 18
Kindler et al JCO 2010

85. AViTA: study design
 Stratified according to country, KPS (<80% vs
≥80%), albumin level (<2.9g/dL vs ≥2.9g/dL)
PD
Previously
untreated
metastatic
pancreatic cancer
GE-B
(n=306)
GE-P
(n=301)
B = bevacizumab
KPS = Karnofsky performance status
PD = progressive disease
Gemcitabine: 1,000mg/m2 on days 1, 8, 15, 22, 29, 36, 43 for first 8 weeks, days 1, 8, 15 in
subsequent 4-week cycles; Erlotinib 100mg/day; Bevacizumab 5mg/kg q2w
PD
1:1
R
A
N
D
O
M
I
Z
A
T
I
O
N
Vervenne W, Van Cutsem E, et al. J Clin Oncol
2008;26(Suppl.):214s (Abs. 4507)
Van Cutsem E et al, accepted J Clin Oncol 2009

86. AViTA objectives and inclusion/
exclusion criteria Primary endpoint:
– OS
 Secondary endpoints:
– Progression-free survival (PFS), response rate, and safety (adverse
events [AEs] graded by NCI-CTC v3.0)
 Exploratory analysis
– OS, PFS, and disease control rate according to occurrence and grade
of rash
 Inclusion criteria
– histologically confirmed, metastatic pancreatic adenocarcinoma; no prior
therapy for metastatic disease; >6 months since adjuvant therapy; no
prior gemcitabine or anti-vascular endothelial growth factor (VEGF)
therapy; KPS ≥60; adequate hematologic, hepatic, and renal function
 Exclusion criteria
– invasion of major blood vessels; surgery in last 28 days; bleeding
disorders; significant cardiovascular disease

87. OS and PFS in AViTA
1.0
0.8
0.6
0.4
0.2
0
0 3 6 9 12 15 18 21 24
OSprobability
GE-B
(n=221 with events)
GE-P
(n=233 with events)
Time (months)
7.16.0
p=0.2087 HR=0.89
(95% CI: 0.74–1.07)
OS
p=0.0002 HR=0.73
(95% CI: 0.61–0.86)
PFS
Vervenne W, Van Cutsem E, et al. J Clin Oncol 2008;26(Suppl.):214s (Abs. 4507)
GE-B
(n=257 with events)
GE-P
(n=278 with events)
0 3 6 9 12 15 18 21 24
Time (months)
1.0
0.8
0.6
0.4
0.2
0
PFSprobability
4.63.6

88. Incidence of AEs in both treatment
arms
GE-P
(n=287)
GE-B
(n=296)
AE, %a Any grade Grade 3/4 Any grade Grade 3/4
Hematologic
Anemia
Thrombocytopenia
Neutropenia
33
26
26
9
7
17
27
30
29
7
8
21
Non-hematologic
Diarrheaa
Nausea
Rash
Vomiting
Pyrexia
Fatigue
Constipation
Anorexia
Epistaxis
Peripheral edema
Abdominal pain
Asthenia
Hypertension
51
51
44
42
37
34
23
24
11
17
15
15
9
6
3
3
4
2
7
<1
2
0
1
1
6
1
49
46
49
37
34
33
27
21
29
17
16
14
19
4
4
8
5
3
5
1
2
<1
<1
3
5
3
aOne patient in the placebo arm had a grade 5 event

89. Baseline characteristics by grade of
rash
Skin rash
NCI-CTC grade 0 NCI-CTC grade 1 NCI-CTC grade ≥ 2
GE-P
(n=123)
GE-B
(n=91)
GE-P
(n=101)
GE-B
(n=215)
GE-P
(n=77)
GE-B
(n=105)
Gender, male/female, % 64/36 46/54 55/45 57/43 69/31 66/34
<65 years / ≥65 years, % 59/41 56/44 68/32 61/39 68/32 61/39
Smoking status
Current/Former/Never, % 30/27/42 30/25/44 18/37/45 14/37/49 10/39/51 8/38/54
Pack years, median (range) 30.0
(3–162)
30.0
(3–120)
20.0
(0–105)
25.0
(0–100)
20.0
(0–80)
20.0
(1–135)
Laboratory parameters, %
Albumin, < or ≥ 2.9g/dL 7/93 8/92 2/98 5/95 4/96 3/97
LDH, ≤ or > ULN 67/33 68/32 72/28 68/32 67/33 63/37
Alkaline phosphatase, ≤ or
>484U/L
85/15 88/12 91/9 89/11 86/14 89/11
CRP, ≤ or >1.4mg/dL 36/64 34/66 55/45 62/38 61/39 49/51
CA19, ≤ or >1350kU/L 41/59 47/53 60/40 49/51 70/30 51/49
Neutrophils, ≤ or >ULN 75/25 78/22 87/13 80/20 86/14 78/22

90. OS
1.0
0.8
0.6
0.4
0.2
0
No. left
All gr 0 214 78 12 1 0
All gr 1 211 121 20 0 0
All gr 2 182 119 26 2 0
All grade 0
All grade 1
All grade 2
0 6 12 18 24
Time (months)
OS
1.0
0.8
0.6
0.4
0.2
0
No. left
All gr 0 214 78 12 1 0
All gr 1 393 240 46 2 0
All grade 0
All grade 1
0 6 12 18 24
Time (months)
p<0.0001 HR=0.54
(95% CI: 0.44–0.65)
OS relative to rash
0 6 12 18 24
OS
1.0
0.8
0.6
0.4
0.2
0
No. left
GE-B gr 0
GE-B gr 1
GE-P gr 0
GE-P gr 1
Time (months)
91 37 3 0 0
215 137 25 1 0
123 41 9 1 0
178 103 21 1 0
GE-B grade 0
GE-B grade  1
GE-P grade 0
GE-P grade  1

91. OS according to severity of rash
OS (months [95% CI])
No rash Grade 1 rash Grade ≥2 rash Any rash
GE-P arm 4.3 (3.4–5.4) 7.1(6.1–9.6) 8.3 (6.0–10.7) 8.1 (6.6–9.6)
HR=0.56
(95% CI: 0.41–0.76)
p=0.0001
HR=0.50
(95% CI: 0.36–0.70)
p<0.0001
HR=0.53
(95% CI: 0.41–0.68)
p<0.0001
GE-B arm 5.0 (3.9–6.4) 7.4 (5.8–9.1) 8.4 (7.2–10.2) 7.9 (7.1–9.1)
HR=0.60
(95% CI: 0.44–0.83)
p=0.0017
HR=0.49
(95% CI: 0.35–0.69)
p<0.0001
HR=0.54
(95% CI: 0.41–0.72)
p<0.0001
All patients 4.8 (3.7–5.4) 7.4 (6.4–9.1) 8.4 (7.2–9.9) 8.0 (7.1–9.1)
HR=0.59
(95% CI: 0.47–0.73)
p<0.0001
HR=0.50
(95% CI: 0.39–0.63)
p<0.0001
HR=0.54
(95% CI: 0.44–0.65)
p<0.0001
N.B. All hazard ratios (HRs) are for rash versus no rash

92. PFS
1.0
0.8
0.6
0.4
0.2
0
No. left
All gr 0 214 36 0 0 0
All gr 1 393 122 15 1 0
All grade 0
All grade 1
0 6 12 18 24
Time (months)
p<0.0001 HR=0.53
(95% CI: 0.44–0.63)
PFS relative to rash
0 6 12 18 24
No. left
All gr 0 214 36 0 0 0
All gr 1 211 54 6 0 0
All gr 2 393 122 15 1 0
PFS
1.0
0.8
0.6
0.4
0.2
0
All grade 0
All grade 1
All grade 2
Time (months)
PFS
1.0
0.8
0.6
0.4
0.2
0
No. left
GE-B gr 0 91 21 0 0 0
GE-B gr 1 215 77 10 1 0
GE-P gr 0 123 15 0 0 0
GE-P gr 1 178 45 5 0 0
0 6 12 18 24
Time (months)
GE-B grade 0
GE-B grade  1
GE-P grade 0
GE-P grade  1

93. PFS according to severity of rash
PFS (months (95% CI])
No rash Grade 1 rash Grade ≥2 rash Any rash
GE-P arm 2.1 (1.9–2.8) 3.7 (3.6–4.2) 4.1 (3.6–5.5) 3.8 (3.7–4.7)
HR=0.67
(95% CI: 0.51–0.88)
p=0.0033
HR=0.47
(95% CI: 0.34–0.64)
p<0.0001
HR=0.56
(95% CI: 0.44–0.71)
p<0.0001
GE-B arm 3.0 (2.1–3.9) 4.0 (3.4–5.4) 5.8 (5.4–7.3) 5.4 (4.5–5.8)
HR=0.61
(95% CI: 0.45–0.83)
p=0.0011
HR=0.45
(95% CI: 0.33–0.62)
p<0.0001
HR=0.52
(95% CI: 0.40–0.68)
p<0.0001
All patients 2.5 (2.0–3.0) 3.8 (3.6–4.4) 5.5 (4.7–6.0) 4.6 (3.9–5.3)
HR=0.62
(95% CI: 0.51–0.76)
p<0.0001
HR=0.44
(95% CI: 0.35–0.55)
p<0.0001
HR=0.53
(95% CI: 0.44–0.63)
p<0.0001
N.B. All HRs are for rash versus no rash

94. Study Schema for Phase III Trial of
Gemcitabine vs FOLFIRINOX
Prodige 4 - ACCORD 11
Metastatic PDAC
n = 342
Gemcitabine 1000 mg/m2
weekly x 7 of 8,
then weekly x 3 of 4
(n = 171)
FOLFIRINOX
Oxaliplatin 85 mg/m2
LV 400 mg/m2
Irinotecan 180 mg/m2
5-FU bolus 400 mg/m2, then
2400 mg/m2 infusional over
46 hrs (n = 171)
Stratified by ECOG PS (0 vs 1), center,
tumor location (head vs other)
Conroy T, et al. N Eng J Med. 2011;364:1817-1825.

95. Flow Chart
Folfirinox Gemcitabine Total
Total randomized 171 171 342
Did not fulfill all
eligibility criteria
8* 7* 15 (4%)
Untreated patients 4 2 6 (2%)
ITT population 171 171 342 (100%)
Safety population 167 169 336 (98%)
*Folfirinox arm : 2 patients > 76 years; one patient PS=2;
5 patients with high bilirubin, high creatinine or low platelets
*Gemcitabine arm: 7 patients with high bilirubin, high creatinine or low platelets
Conroy et al, NEJM 2011

96. Patients characteristics
Characteristic
Folfirinox
N=171
Gemcitabine
N=171
p
Median age (yrs)
[range]
61
[25-76]
61
[34-75]
NS
Sex Male
Female
106 (62%)
65 (38%)
105 (61.4%)
66 (38.6%) NS
Baseline PS 0
1
2
64 (37.4%)
106 (62.0%)
1 (0.6%)
66 (38.6%)
105 (61.4%)
0 (0.0%)
NS
Location of primary Head
Other
62 (36.3%)
109 (63.7%)
60 (35.1%)
111 (64.9%) NS
Conroy et al, NEJM 2011

97. Disease characteristics
Characteristic
Folfirinox
N=171
Gemcitabine
N=171
p
Synchronous metastases
Metachronous metastases
156 (91.2%)
15 (8.8%)
161 (94.2%)
10 (5.8%)
NS
NS
Median nr. of involved sites
CA19-9  59 ULN
2 (1-6)
68 (41.5%)
2 (1-6)
77 (46.7%)
NS
NS
Measurable site
Liver
Pancreas
Nodes
Lungs
Peritoneal
149 (88.2%)
89 (52.7%)
48 (28.4%)
33 (19.5%)
33 (19.5%)
150 (87.7%)
91 (53.2%)
39 (22.8%)
49 (28.7%)
32 (18.7%)
NS
NS
NS
0.049
NS
Conroy et al, NEJM 2011

98. Objective Response Rate
Folfirinox
N=171
Gemcitabine
N=171
p
Complete response 0.6% 0%
Partial response 31% 9.4% 0.0001
CR/PR 95% CI [24.7-39.1] [5.9-15.4]
Stable disease 38.6% 41.5%
Disease control
CR+PR+SD
70.2% 50.9% 0.0003
Progression 15.2% 34.5%
Not assessed 14.6% 14.6%
Median duration
of response
5.9 mo. 4 mo. ns
Conroy et al, NEJM 2011

99. FOLFIRINOX vs Gemcitabine: OS
and PFS
OS PFS
100
75
50
0
0 3 6 9 12 15 18 21 24 27 42
Months
PatientsAlive(%)
25
39363330
Gemcitabine
FOLFIRINOX
HR: 0.57 (95% CI: 0.45-0.73;
P < .001 by stratified log-rank test)
Gemcitabine
FOLFIRINOX
Pts at Risk, n
171 134 89 48 28 14 7 6 3 3 12222
171 146 116 81 62 34 20 13 9 5 22223
100
75
50
0
0 3 6 9 12 15 18 21 36
MonthsPatientsWithoutProgresion(%)
25
33302724
Gemcitabine
FOLFIRINOX
HR: 0.47 (95% CI: 0.37-0.59;
P < .001)
Gemcitabine
FOLFIRINOX
Pts at Risk, n
171 88 26 8 5 2 0 0 00000
171 121 85 42 17 7 4 1 00001
Conroy T, et al. N Eng J Med. 2011;364:1817-1825.

100. Overall Survival
Folfirinox
N=171
Gemcitabine
N=171
p HR
Median survival
[CI 95%]
11.1 mo.
[ 9 - 13.1]
6.8 mo.
[ 5.5 - 7.6]
<0.0001 0.57
1-yr. survival 48.4% 20.6%
18-mo. survival 18.6% 6%
Median follow up: 26.6 months [95% CI: 20.5 – 44.9]
Conroy et al, NEJM 2011

101. Safety: hematological AEs
AE, % per patient
Folfirinox
N=167
Gemcitabine
N=169
p
All Grade 3/4 All Grade 3/4 Grade 3/4
Neutropenia 79.9 45.7 54.8 18.7 0.0001
Febrile Neutropenia 7.2 2.4 0.6 0.009
Anemia 90.4 7.8 94.6 5.4 NS
Thrombocytopenia 75.2 9.1 54.8 2.4 0.008
5.4
42.5 % of the pts received G-CSF in the F arm vs 5.3% in the G arm
One toxic death occurred in each arm
AE, adverse event
Conroy et al, NEJM 2011

102. Safety: main non-hematological AEs
AE, % per patient
Folfirinox N=167 Gemcitabine N=169
p
All Grade 3/4 All Grade 3/4
Infection without
neutropenia
6 1.2 7.1 1.8 NS
Peripheral neuropathy 70.5 9 0.6 0 0.0001
Vomiting 61.4 14.5 43.2 4.7 0.002
Fatigue 87.3 23.2 78.7 14.2 0.036
Diarrhea 73.3 12.7 30.8 1.2 0.0001
Alopecia (grade 2) 32.5 (11.4) 3.0 (0.6) 0.0001
ALT 64.8 7.3 83.8 0.002218.6
Conroy et al, NEJM 2011

103. Phase III MPACT Trial: Gemcitabine ± nab-
Paclitaxel in Metastatic Pancreatic Cancer
 Primary objective: OS
 Secondary endpoints: PFS, ORR, safety
Von Hoff DD, et al. NEJM 2013
Patients with
metastatic pancreatic
cancer, no previous
treatment for
metastatic disease,
KPS ≥ 70, bilirubin
≤ ULN
(N = 861)
nab-Paclitaxel 125 mg/m2 IV q3w +
Gemcitabine 1000 mg/m2
on Days 1, 8, 15 q4w
(n = 431)
Gemcitabine 1000 mg/m2/wk for
7 wks, and then on Days 1, 8, 15 q4w
(n = 430)
Treat until
PD
Stratified by KPS, region, liver metastasis

104. MPACT Trial of Gemcitabine ± nab-
Paclitaxel in Metastatic Pancreatic Cancer:
OS
Von Hoff DD, et al. ASCO 2013. Abstract 4005. Used with permission.
1.0
0.9
0.8
0.7
1.6
0.5
0.4
0.3
0.2
0.1
0
0 3 6 9 12 15 18 21 24 27 30 33 36 39
Mos
ProportionofSurvivingPatients
nab-P + gem
OS, Mos
Events,
n/N (%)
Median
(95% CI)
75th
Percentile
333/431 (77) 8.5 (7.89-9.53) 14.8
359/430 (83) 6.7 (6.01-7.23) 11.4
Gem
HR: 0.72
(95% CI: 0.617-0.835;
P = .000015)
431
430
357
340
269
220
169
124
108
69
67
40
40
26
27
15
16
7
9
3
4
1
1
0
1
0
0
0
Pts at Risk, n
nab-P + gem
Gem

105. Gemcitabine ± nab-Paclitaxel in Metastatic
Pancreatic Cancer: PET & CA19-9 Correlates
Von Hoff DD, et al. ASCO 2013. Abstract 4005. Used with permission.
Metabolic Response by PET (Independent Review)
Outcome
nab-P + Gem
(n = 130)
Gem
(n = 127)
HR P Value
Metabolic response by PET, % 63 38 -- .000051
ORR by CT, % 31 11 -- .0001
Median OS in PET cohort, mos 10.5 8.3 0.71 .0096
Predictive Value of CA19-9 Response at Wk 8 on OS: Landmark Analyses
Decrease in CA19-
9 Level at Wk 8
nab-P + Gem
(n = 130)
Gem
(n = 127)
HR P Value
n
Median
OS, Mos
n
Median
OS, Mos
≥ 20% 197 13.2 141 9.4 0.59 < .0001
≥ 90% 59 13.4 34 9.8 0.47 .0053
Significantly more patients experienced ≥ 20% and ≥ 90% reductions in CA19-9 with the
addition of nab-paclitaxel (P < .0001)

106. MPACT Trial of Gemcitabine ± nab-
Paclitaxel in Metastatic Pancreatic Cancer:
AEs
AE nab-P + Gem (n = 421) Gem (n = 402)
≥ 1 AE leading to death, % 4 4
Grade ≥ 3 hematologic AE,* %
 Neutropenia 38 27
 Leukopenia 31 16
 Thrombocytopenia 13 9
 Anemia 13 12
Receipt of growth factors % 26 15
Febrile neutropenia†, % 3 1
Grade ≥ 3 nonhematologic AE† in > 5% patients, %
 Fatigue 17 7
 Peripheral neuropathy 17 < 1
 Diarrhea 6 1
Grade ≥ 3 neuropathy
 Time to onset, median days 140 113
 Time to improvement by grade, median days 21 29
 Time to improvement to grade ≤ 1, median days 29 --
 Resumed nab-paclitaxel, % 44 --
Von Hoff DD, et al. ASCO 2013. Abstract 4005. Used with permission.
*Based on lab values. †Based on investigator assessment of treatment-related events.

107. MPACT Trial of Gem ± nab-Paclitaxel in
Metastatic Pancreatic Cancer: Conclusions
 Addition of nab-paclitaxel to gemcitabine significantly improved
survival
– Across entire curve at all time points
– Median OS: 8.5 vs 6.7 mos with gemcitabine alone
 Metabolic response rates (by PET and CA19-9) significantly
increased with addition of nab-paclitaxel to gemcitabine
– Predictive of OS
 Serious AEs not increased, remain acceptable and manageable
 Nab-paclitaxel + gemcitabine potentially a new standard for the
treatment of metastatic pancreatic cancer
– Could become backbone of new regimens
Von Hoff DD, et al. ASCO 2013. Abstract 4005. Used with permission.