Tratamento adjuvante em - rvmais.iweventos.com.br · Tumor site Intrahepatic CC Hilar CC...
Transcript of Tratamento adjuvante em - rvmais.iweventos.com.br · Tumor site Intrahepatic CC Hilar CC...
Tratamento adjuvante em Câncer do Trato Biliar
Lucas V. dos Santos
Oncologista Clínico
BP – A Beneficência Portuguesa de São Paulo
Declaração de Conflito de Interesses
Eu declaro não possuir conflito de interesses em relação a esta apresentação.
Tratamento adjuvante em Câncer do Trato Biliar
• O Câncer do trato biliar (CTB) é relativamente incomum, e se associa a prognóstico reservado [1]
• Sobrevida em 1 ano de 22%
• Sobrevida em 5 anos de 9%
• O tratamento cirúrgico pode curar alguns pacientes, com sobrevida em 1 ano atingindo 15% dos casos [2]
• Porém apenas 20% dos casos pode ser operados
• Há controvérsias se o tratamento adjuvante pode ser útil na melhora dos resultados dos pacientes com CTB operados[3]
1. Khan SA, et al. J Hepatol. 2012;56:848-854. 2. Office for National
Statistics. 1999. https://www.springer.com/gp/book/9780116210319. 3.
Primrose JN , et al. ASCO 2017. Abstract 4006.
Tratamento adjuvante em Câncer do Trato Biliar
Nakeeb A, Pitt HA, Sohn TA, et al. Ann Surg. 1996;224(4):463; Fong Y, Blumgart LH, Lin E, et al. Br J Surg.
1996;83(12):1712. DeOliveira ML, Cunningham SC, Cameron JL, et al Ann Surg. 2007;245(5):755. Nakayama F, Miyazaki
K, Nagafuchi K. World J Surg. 1988;12(1):60; Bortolasi L, Burgart LJ, Tsiotos GG, et al. Dig Surg. 2000;17(1):36;
Murakami Y, Uemura K, Hayashidani Y, et al. World J Surg. 2007;31(2):337; Yoshida T, Matsumoto T, Sasaki A, et al.
Arch Surg. 2002;137(1):69; Lieser MJ, Barry MK, Rowland C,et al. J Hepatobiliary Pancreat Surg. 1998;5(1):41; Valverde
A, Bonhomme N, Farges O, et al. J Hepatobiliary Pancreat Surg. 1999;6(2):122. Cameron JL, Pitt HA, Zinner MJ et al.
Am J Surg. 1990;159(1):91; , Fortner JG, Vitelli CE, Maclean BJ Arch Surg. 1989;124(11):1275
Sobrevida em 5 anos
Intra-hepático Extra-hepático
Hilar
LN(-) e/ou R0 44-63% 20-50% 30-62%
LN(+) e/ou R1 11-20% <20% <20%**Contaminação por câncer peri-ampular, de melhor prognóstico
Tratamento adjuvante em Câncer do Trato Biliar
Horgan AM et al. J Clin Oncol. 2012 Jun 1;30(16):1934-40
20 estudos, 6712 pacientes
Tratamento adjuvante em Câncer do Trato Biliar
Horgan AM et al. J Clin Oncol. 2012 Jun 1;30(16):1934-40
20 estudos, 6712 pacientes
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Study Design• Open-label, randomized, controlled phase III trial
Primrose JN , et al. ASCO 2017. Abstract 4006.
Primary endpoint: OS
Secondary endpoints: RFS, toxicity, QoL, health economics
Capecitabine 1250 mg/m2 BID
Days 1-14 of 21-day cycle for 8 cycles
(n = 223)
Observation
(n = 224)
Histologically confirmed
biliary tract cancer*; radical
and macroscopically
complete surgery; ECOG
PS ≤ 2; no previous
chemotherapy or
radiotherapy for biliary
tract cancer
(N = 447)
Primary
analysis after
minimum 2-yr
follow-up
Resection
*Included: intrahepatic CC, hilar CC, muscle-invasive gallbladder cancer, and lower common bile duct CC
Excluded: pancreatic, ampullary, mucosal (T1a) gallbladder cancers; incomplete recovery from prior surgery
Stratified by surgical center,
R0 vs R1 resection, ECOG PS
BILCAP: Sample Size Calculation
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Flowchart
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Baseline CharacteristicsCharacteristic, % Capecitabine Arm
(n = 223)Observation Arm
(n = 224)
Male 50 50
Median age, yrs (IQR) 62 (55-68) 64 (55-69)
Tumor site Intrahepatic CC Hilar CC Muscle-invasive gall bladder carcinoma Lower common bile duct CC
19291734
18281836
Resection status, R0/R1 62/38 63/38
ECOG PS, 0/1/2 45/52/3 45/52/3
Tumor size, mm (IQR) 25 (19-45) 25 (20-44)
Lymph node status, N0/N1/not evaluable 45/48/7 48/46/6
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Treatment Compliance• Median capecitabine dose: 1250 mg/m2 BID (IQR: 1061-1250 mg/m2)
01 50 100 150 200 223
2
4
6
8
Cycle
s o
f C
ap
ecit
ab
ine
(n
)
Pts (n)
122 (55%) pts in the capecitabine
arm received 8 cycles
10 (< 5%) pts
received 0 cycles
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: OSITT Population
Treatment Median OS, Mos (95% CI)
HR (95% CI)
Capecitabine 51.1 (34.6-59.1) 0.81 (0.63-1.04)P = .097Observation 36.4 (29.7-44.5)
Sensitivity analyses adjusting for further prognostic factors (gender, nodal status, disease grade) HR 0.70 (95% CI: 0.55-0.91; P = .007)
Treatment Median OS, Mos (95% CI)
HR (95% CI)
Capecitabine 52.7 (40.3-NR) 0.75 (0.58-0.97)P = .028Observation 36.1 (29.6-44.2)
Per Protocol Population
> 80% pts followed-up for 36 mos
0
25
50
75
100
Pts
Ali
ve (
%)
0 12 24 36 48 60Mos Since Randomization
0
25
50
75
100
Pts
Ali
ve (
%)
0 12 24 36 48 60Mos Since Randomization
Primrose JN , et al. ASCO 2017. Abstract 4006.
Primrose JN , et al. ASCO 2017. Abstract 4006.
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: OS Subgroup Analysis
Primrose JN , et al. ASCO 2017. Abstract 4006.
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Relapse-Free Survival
Treatment Median RFS, Mos (95% CI)
HR (95% CI)
Capecitabine 24.6 (18.9-36.7) 0.76 (0.58-0.99)P = .039Observation 17.6 (12.8-27.6)
Treatment Median RFS, Mos (95% CI)
HR (95% CI)
Capecitabine 25.9 (19.8-46.3) 0.71 (0.54-0.92)P = .011Observation 17.6 (12.0-23.8)
0
25
50
75
100
Pts
Recu
rren
ce F
ree (
%)
0 12 24 36 48 60Mos Since Randomization
0
25
50
75
100
0 12 24 36 48 60
ITT Population Per Protocol Population
Pts
Recu
rren
ce F
ree (
%)
Mos Since Randomization
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Safety and QoL• Safety population included 213 patients who received capecitabine Adverse Event, n (%) All Grades Grades
1/2Grades
3/4
Fatigue 175 (82) 159 (75) 16 (8)
Plantar-palmar erythema 174 (82) 130 (61) 44 (21)
Diarrhea 137 (64) 121 (57) 16 (8)
Nausea 108 (51) 106 (50) 2 (1)
Mucositis/stomatitis 96 (45) 94 (44) 2 (1)
Vomiting 50 (24) 49 (23) 1 (0.5)
Neutropenia 49 (23) 45 (21) 4 (2)
Hyperbilirubinemia 45 (21) 42 (20) 3 (1)
Thrombocytopenia 26 (12) 25 (12) 1 (0.5)
Alopecia 20 (9) 20 (9) 0 (0)
SAE n (%)
All 93 (44)
Pts with ≥ 1 SAE 69 (32)
SAEs by treatment arm n
Capecitabine arm SAE
47 (64 events)30 (33 events)
Observation arm SAE resulting in death
22 (29 events)3
QoL was not reduced in
capecitabine arm compared with
placebo
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: QoL
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Author’s Conclusions
• Adjuvant capecitabine associated with improved OS in pts with resected biliary tract cancer
• Authors suggest capecitabine should become standard of care in this setting
• Capecitabine treatment produced modest toxicity
• QoL in capecitabine arm comparable to observation arm
• Authors recommend using capecitabine control arm in future adjuvant trials in biliary tract cancer
Primrose JN , et al. ASCO 2017. Abstract 4006.
BILCAP: Minhas Conclusões
• Adjuvant capecitabine associated with does not improved OS in pts with resected biliary tract cancer
• I suggest capecitabine should NOT become standard of care in this setting
• Capecitabine treatment produced IMPORTANT toxicity
• QoL in capecitabine arm comparable to observation arm
• Authors recommend using capecitabine control arm in future adjuvant trials in biliary tract cancer
Primrose JN , et al. ASCO 2017. Abstract 4006.
"There are three kinds of lies: lies, damned lies, and statistics."
Benjamin Disraeli, 1804-1881