Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin

Figures & data

Figure 1. Flow chart. ErasmusMC, Erasmus Medical Center. AMC, Amsterdam Medical Center. The ErasmusMC cohort consists of only perihilar cholangiocarcinoma patients and some additional BTC patients from a systematic search in the pharmacy registers. The AMC cohort consists of all unresectable BTC patients between January 2010 and January 2015. BTC was defined as intra- or extrahepatic cholangiocarcinoma or gallbladder cancer.

Table 1. Did not meet the criteria of the ABC-02 trial based on.

Variable	Group II (N= 64)
Age >18 years n (%)	0 (0.0)
Histological or cytologic diagnosis n (%)	5 (7.8)
ECOG PS n (%)	1 (1.5)
Serum bilirubin level >1.5 times ULN n (%)	15 (23.4)
Serum liver-enzyme levels >5 times ULN n (%)	55 (85.9)
Serum ureum and creatinine level >1.5 times ULN n (%)	2 (3.1)
eGFR <45ml/min n (%)	2 (3.1)

ECOG PS: Eastern Cooperative Oncology Group performance status; ULN: upper limit of normal; eGFR: calculated glomerular filtration.

Liver enzyme levels including: alanine-transaminase, aspartate-transaminase, gamma-glutamyltransferase and alkaline phosphatase.

Table 2. Patients characteristics.

Variable	Chemotherapy in daily practice (N= 138)	Gem–Cis arm ABC-02 Trial (N = 204)	Group I (N = 74)	Group II (N= 64)	p-Value	Group III (N= 70)
Age in years
Median	63	63.9	64	63	.504	72
Range	35–79	32.8–81.9	35–77	40–79	–	41–86
Sex- no. (%)					.431
Female	61 (44.2)	108 (52.9)	35 (47.3)	26 (40.6)	–	34 (48.6)
Male	77 (55.8)	96 (47.1)	39 (52.7)	38 (59.4)	–	36 (51.4)
Extent of disease – no. (%)					.094
Locally advanced	38 (27.5)	55 (27.0)	16 (21.6)	22 (34.4)	–	32 (46.4)
Metastatic	100 (72.5)	149 (73.0)	58 (78.4)	42 (65.6)	–	36 (52.2)
Primary tumor site – no. (%)					.099
Gallbladder	25 (18.1)	73 (35.8)	17 (23.0)	8 (12.5)	–	14 (20.6)
Bile duct	100 (72.5)	122 (59.8)	48 (64.9)	52 (81.3)	–	46 (67.6)
Ampulla	7 (5.1)	9 (4.4)	6 (8.1)	1 (1.6)	–	6 (8.8)
Unclear	6 (4.3)	0	3 (4.1)	3 (4.7)	–	2 (2.9)
ECOG performance-status score – no. (%)					.543
0	52 (37.7)	66 (32.4)	30 (40.5)	23 (35.9)	–	16 (22.9)
1	72 (52.2)	111 (54.4)	37 (50.0)	35 (54.7)	–	20 (28.6)
2	11 (8.0)	27 (13.2)	7 (9.5)	4 (6.3)	–	8 (11.4)
3	1 (0.7)	0	0	1 (1.6)	–	3 (4.3)
Unknown	2 (1.4)	0	0	1 (1.6)	–	23 (32.9)
Previous therapy – no. (%)					.073
No	31 (22.5)	50 (24.5)	21 (28.4)	10 (15.6)	–	6 (8.8)
Yes	107 (77.5)	154 (75.5)	53 (71.6)	54 (84.4)	–	62 (91.2)
Type of previous therapy –no. (%)
Surgery	62 (44.9)	74 (36.2)	35 (47.3)	27 (42.2)	.547	31 (45.6)
Biliary stenting	64 (46.4)	93 (45.6)	–	–	–	–
PTC-drain	–	–	5 (6.8)	17 (26.6)	.002	15 (22.1)
ERCP with biliary stenting	–	–	39 (39.2)	35 (54.7)	.069	44 (64.7)
Radiotherapy	5 (3.6)	3 (1.5)	2 (2.7)	2 (3.1)	.883	3 (4.4)
Other therapy	37 (26.8)	76 (37.3)	9 (12.2)	6 (9.4)	.600	5 (7.4)
BMI (kg/m^2)
Median	–	–	24.7	23.4	.286	24.2
Range	–	–	16.7–38.0	17.2–52.1	–	16.0–38.6

Gem–Cis arm: gemcitabine plus cisplatin tretment arm of the ABC-02 trial; PTC: percutaneous transhepatic cholangiography; ERCP: endoscopic retrograde cholangiopancreatography; BMI: body mass index; ECOG: Eastern Cooperative Oncology Group. Bile duct includes intrahepatic, hilar- and extra- hepatic cholangiocarcinoma. p-Values are calculated for the comparison of group I vs. group II.

Figure 2. Survival rates: (A) overall survival, (B) progression-free survival.

Table 3. Treatment and outcomes.

Variable	Group I (N = 73)	Group II (N = 64)	p-Value
Cycles per patient			.688
Median (range)	6 (1–16)	6 (1–16)	–
Dose gemcitabine (mg/m^2)			.286
Median (range)	17400 (1720–55186)	19200 (1910–51200)	–
Dose cisplatin (mg/m^2)			.544
Median (range)	425 (25–1388)	482 (48–1388)	–
Dose reduction – no. (%)			.974
No	50 (68.5)	44 (68.8)	–
Yes	23 (31.5)	20 (31.3)	–
Dose intensity gemcitabine – no. (%)			.550
≥95%	23 (31.9)	25 (39.7)	–
85–94%	16 (22.2)	11 (17.5)	–
75–84%	10 (13.9)	5 (7.9)	–
<75%	23 (31.9)	22 (34.9)	–
Dose intensity cisplatin – no. (%)			.343
≥95%	20 (27.8)	26 (41.3)	–
85–94%	17 (23.6)	12 (19.0)	–
75–84%	8 (11.1)	8 (12.7)	–
<75%	27 (37.5)	17 (27.0)	–
Reason chemotherapy stopped – no. (%)			.729
Toxicity	14 (19.2)	10 (15.6)	–
Progressive disease	25 (34.2)	26 (40.6)	–
Other reason	16 (21.9)	16 (25.0)	–

For one patient in both groups dose intensity could not be calculated.

Table 4. Grade 3 or 4 toxic effects during treatment.

Variable	Chemotherapy in daily practice (N = 137)	Group I (N = 73)	Group II (N = 64)	p-Value
Hematologic toxic effects – no. (%)
Decreased white-cell count	16 (11.7)	9 (12.3)	7 (10.9)	.153
Decreased platelet count	18 (13.1)	6 (8.2)	12 (18.8)	.079
Decreased haemoglobin count	9 (6.6)	6 (8.2)	3 (4.7)	.289
Decreased neutrophil count	45 (32.8)	26 (35.6)	19 (29.7)	.423
Liver function – no. (%)
Increased alanine aminotransferase level	6 (4.4)	4 (5.5)	2 (3.1)	.503
Other abnormal liver function	26 (19.0)	10 (13.7)	16 (25.0)	.224
Non-hematologic toxic effects – no. (%)
Infection	–	8 (11.0)	6 (9.4)	.941
Fatigue/nausea/vomiting	–	3 (4.1)	2 (3.1)	.867
Renal function	–	2 (2.7)	0	.407

Toxicity according to CTCAE 4.0. For one patient in group I, there were no data available on toxicity. p-Values were calculated for the comparison of group I vs. group II.