Identification of patients with advanced pancreatic cancer who might benefit from third-line chemotherapy

Table 1 Baseline characteristics, n (%)

		Third-line chemotherapy (n = 141)	Best supportive care (n = 167)	P value
Mean age (year, range)		61.8 (36.0-86.0)	59.5 (21.0-81.0)	0.200
Gender	Male	78 (54.9)	102 (61.1)	0.277
Initial tumor location	Head/body/tail	51/45/45 (36.6/31.7/31.7)	68/42/57 (40.7/25.2/34.1)	0.011
Initial stages	Locally advanced/metastatic	32/109 (22.5/76.8)	60/106 (36.1/63.9)	0.010
Initial metastatic lesions	Liver/peritoneum/other	74/36/56 (67.9/37.0/51.4)	70/32/22 (41.9/19.2/13.2)	< 0.001
Median CA19-9 before (U/mL) (SD)	First-/second-/third-line CTx	450/655/1820 (9231.4/7865.2/10901.9)	330/480/NA (8447.3/8257.0/NA)	0.248/0.298/NA
CA19-9 before third-line CTx (n = 134)	< 1000/≥ 1000 U/mL	49/85 (36.6/63.4)
First-line regimen	FOLFIRINOX/GNP	95/46 (67.4/32.6)	122/45 (73.1/26.9)	0.241
Second-line regimen	FOLFIRINOX/GNP/TS-1/nal-IRI plus 5FU and leucovorin/other	38/74/3/8/18 (27.0/52.5/2.1/5.7/12.8)	36/110/9/5/7 (21.6/65.9/5.4/3.0/4.2)	< 0.001
Third-line regimen	TS-1/nal-IRI plus 5FU and leucovorin/other	68/53/20 (48.2/37.6/14.2)
Median duration (week)	First/second-line CTx	27.2/16.0 (29.0/15.9)	27.4/11.9(46.3/19.7)	0.797/0.800
Duration of second-line CTx	< 19 weeks/≥ 19 weeks	89/52 (63.1/36.9)	127/30 (80.9/19.1)	< 0.001
Median relative dose	First-/second-/third-line CTx	74/78/100 (0.18/0.17/0.19)
PS after second-line CTx	Good/intermediate/poor	118/23/0 (83.7/16.3/0.0)	3/69/95 (1.8/41.3/56.9)	< 0.001

SD: Standard deviation; NA: Not available; CTx: Chemotherapy; CA19-9: Carbohydrate antigen 19-9; FOLFIRINOX: 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin; GNP: Gemcitabine plus nab-paclitaxel; TS-1: Titanium silicate-1; 5FU: 5-fluorouracil; nal-IRI: Nano-liposomal irinotecan; PS: Performance status.

Table 2 Overall summary of efficacy in third-line chemotherapy

	(n = 141)
Best response, n (%)
PR	2 (1.4)
SD	35 (24.8)
PD	84 (59.6)
NA	20 (14.2)
Disease control rate (CR + PR + SD)	37 (26.2)
Median survival from third-line chemotherapy, weeks (95%CI)
OS3	15.3 (12.9-17.7)
PFS (n = 110)	7.3 (6.3-8.3)
Median survival from diagnosis, months (95%CI)
OS	19.0 (16.6-21.4)

CI: Confidence interval; CR: Complete response; NA: Not available; OS: Overall survival; OS3: Overall survival at third-line chemotherapy; PD: Progressive disease; PFS: Progression-free survival; PR: Partial response; SD: Stable disease.

Table 3 Univariable and multivariable analyses of survival outcomes after third-line chemotherapy

	Univariable			Multivariable
	HR	95%CI	P value	HR	95%CI	P value
Sex (female)	1.39	1.0-2.0	0.062
Age	1.00	1.0-1.0	0.621
Initial stage (locally advanced)	1.15	0.8-1.8	0.511
Intermediate PS at third-line CTx (good PS)	2.22	1.4-3.6	0.001	2.46	1.5-4.1	0.001
CA19-9 (U/mL)
Initial	1.00	1.0-1.0	0.596
≥ 1000 U/mL before third-line CTx (< 1000 U/mL)	1.53	1.0-2.2	0.030	1.58	1.1-2.4	0.028
CTx regimen
Third-line CTx (TS-1)	1.07	1.0-1.2	0.253
Duration of the second-line CTx
< 19 weeks (≥ 19 weeks)	1.75	1.2-2.5	0.003	1.50	1.0-2.2	0.037
Metastases
Liver metastases before third-line CTx (no liver metastases)	1.26	0.8-1.9	0.267
Peritoneal seeding before third-line CTx (no peritoneal seeding)	1.42	1.0-2.0	0.047	1.48	1.0-2.2	0.046

PS: Performance status; TS-1: Titanium silicate-1; CI: Confidence interval; CA19-9: Carbohydrate antigen 19-9; HR: Hazard ratio; CTx: Chemotherapy.

Table 4 Adverse events of patients at third-line chemotherapy, n (%)

	Any grade	Grade 3 or more
Fatigue	51 (36.2)	16 (11.3)
Vomiting	38 (27.0)	14 (9.9)
Bone marrow suppression	26 (18.4)	2 (1.4)
Anorexia	20 (14.2)	2 (1.4)
Peripheral neuropathy	18 (12.8)	10 (7.1)
Diarrhea	16 (11.3)	5 (3.5)
Constipation	13 (9.2)	4 (2.9)
Skin rash	1 (0.7)	0 (0)