Efficacy and safety of immune checkpoint inhibitors in advanced pancreatic cancer: A real world study in Chinese cohort

Figures & data

Figure 1. Study design and patient distribution flow chart.

Table 1. Patient characteristics.

Characteristics		n	%
Age (years)	Median (range)	63 (30–80)
	<60	43	41.3
	≥60	61	58.7
Sex	Female	42	40.4
	Male	62	59.6
ECOG	0	27	26.0
	1	74	71.2
	2	3	2.9
Stage	Locally advanced	30	28.8
	Relapse after operation	26	25.0
	Metastatic	48	46.2
Primary tumor location	Head neck	58	55.8
	Body tail	46	44.2
Tumor type	Adenocarcinoma	69	66.3
	Adenosquamous carcinoma	3	2.9
	Unknown	32	30.8
Differentiation	Low	15	14.4
	Middle	29	27.9
	High	4	3.8
	Unknown	56	53.8
Metastic site	Liver	50	48.1
	Lung	8	7.7
	Bone	4	3.8
	Abdominal	22	21.2
	Lymph	11	10.6
	Others	9	7.8
Metastasis organs	M0	30	28.8
	M1	54	51.9
	M ≥ 2	20	19.2
PDL-1 expression	≥1	8	7.7
	<1	16	15.4
	Unknown	80	76.9
TMB	TMB ≥10	7	6.7
	TMB <10	44	42.3
	Unknown	53	51.0
MSS	MSI-H	1	1.0
	MSS	50	48.1
	Unknown	53	51.0
Immunotherapy lines	First	39	37.5
	Second	51	49.0
	Multi-line	14	13.5
Type of anti-PD-1	Pembrolizumab	7	6.7
	Camrelizumab	11	10.6
	Toripalimab	19	18.3
	Sintilimab	43	41.3
	Tislelizuman	24	23.1
Combined use	ICIs + chemo	60	57.7
	ICIs + targeted	37	35.6
	ICIs + vaccine	7	6.7
Combined radio	Yes	47	45.2
	No	57	54.8
Cycles of treatment	Median (range), n	5 (2–22)
Follow-up time	Median (rang), weeks	30 (10–87)

Abbreviations: ECOG, Eastern Cooperative Oncology Group; PD-L1, programmed death-1 ligand; PD-1, programmed cell death protein; TMB, tumor mutation burden; MSS, microsatellite-stable; MSI-H, microsatellite-instability-high; ICIs, immune checkpoint inhibitors.

Figure 2. Kaplan-Meier curves of survival outcomes of patients in the overall population. (A) Overall survival. (B) Progression-free survival.

Figure 3. Swimmer’s plot illustrating times of response and disease progression and durations of response and survival for patients. (a) Patients of complete response and partial response. (b) Patients with stable disease.

Table 2. Activity of immunotherapy in patients with APC in overall population.

Overall population	ORR, n (%) [95%CI]	DCR, n (%) [95%CI]	BOR, n (%)
			CR, n (%)	PR, n (%)	SD, n (%)	PD, n (%)
104	31.7 (23.6–41.2)	72.1 (62.8–79.8)	4 (3.8)	29 (27.9)	42 (40.4)	29 (27.9)

Abbreviations: ORR, include complete and partial response; DCR, include complete and partial response and stable disease; BOR, best overall response; CR, complete response; PR, partial response; SD, stable disease; PD, progression disease.

Figure 4. Kaplan-Meier curves of ICIs plus chemo/target/vaccine with or without radiotherapy in the overall population. (a) Overall survival. (b) Progression-free survival.

Figure 5. Kaplan-Meier curves of ICIs plus chemo/target/vaccine with or without radiotherapy in recurrent and metastasis pancreatic cancer patients. (A) Overall survival. (B) Progression-free survival.

Table 3. Activity of immunotherapy in patients with APC in subgroup analysis.

Populations	Total n.	CR n (%)	PR n (%)	SD n (%)	PD n (%)	ORR n (%) [95%CI]	DCR n (%) [95%CI]
With radio	47	4 (8.5)	21 (44.7)	18 (38.3)	4 (8.5)	53.2 (39.2–66.7)	91.5 (80.1–96.7)
Without radio	57	0 (0)	8 (14.0)	24 (42.1)	25 (43.9)	14.0 (7.3–25.3)	56.1 (43.3–68.2)
Combined chemo	61	3 (4.9)	26 (42.6)	23 (37.7)	9 (14.8)	47.5 (35.5–59.8)	85.3 (74.3–92.0)
Combined targeted	36	0 (0)	2 (5.6)	15 (41.7)	19 (52.8)	5.6 (1.5–18.2)	47.2 (32.0–63.0)
Combined vaccine	7	1 (14.3)	1 (14.3)	4 (57.1)	1 (14.3)	28.6 (8.2–64.1)	85.7 (48.7–97.4)
First line	39	1 (2.6)	22 (56.4)	14 (35.9)	2 (5.1)	59.0 (43.4–72.9)	94.9 (83.1–98.6)
Second line	51	3 (5.9)	4 (7.8)	23 (45.1)	21 (41.2)	13.7 (6.8–25.7)	58.8 (45.2–71.2)
Multi-line	14	0 (0)	3 (21.4)	5 (35.7)	6 (42.9)	21.4 (7.6–47.6)	57.1 (32.6–78.6)

Abbreviations: ORR, include complete and partial response; DCR, include complete and partial response and stable disease; BOR, best overall response; CR, complete response; PR, partial response; SD, stable disease; PD, progression disease; CI, confidence interval.

Figure 6. Kaplan-Meier curves of ICIs combined chemo or targeted or vaccine in the overall population. (a) Overall survival. (b) Progression-free survival.

Figure 7. Kaplan-Meier curves of ICIs combined chemo or targeted in recurrent and metastasis pancreatic cancer patients. (a) Overall survival. (b) Progression-free survival.

Figure 8. Kaplan-Meier curves of ICIs with different lines in the overall population. (A) Overall survival. (B) Progression-free survival.

Figure 9. Kaplan-Meier curves of ICIs with PD-L1 expression positive and negative in the overall population. (a) Overall survival. (b) Progression-free survival.

Figure 10. Kaplan-Meier curves of ICIs with TMB-H and TMB-L in the overall population. (a) Overall survival. (b) Progression-free survival.

Figure 11. Kaplan-Meier curves of ICIs with TMB-H and TMB-L in recurrent and metastasis pancreatic cancer patients. (a) Overall survival. (b) Progression-free survival.

Table 4. Activity of immunotherapy in patients with APC in PD-L1 protein expression and TMB.

Population	Total, n	CR, n (%)	PR n (%)	SD n (%)	PD n (%)	ORR n (%) [95%CI]	DCR n (%) [95%CI]
PD-L1 +	8	2 (25.0)	3 (37.5)	3 (37.5)	0 (0)	62.5 (30.6–86.3)	100.0 (67.6–100.0)
PD-L1 -	16	1 (6.3)	3 (18.8)	9 (56.3)	3 (18.8)	25.0 (10.1–49.5)	81.3 (57.0–93.4)
TMB-H	7	2(28.6)	1 (14.3)	4 (57.1)	0 (0)	42.9 (15.8–75.0)	100.0 (64.6–100.0)
TMB-L	44	1 (2.3)	9 (20.5)	22 (50.0)	12 (27.3)	22.7 (12.8–37.0)	72.7 (58.2–83.7)

Abbreviations: PD-L1, programmed death-1 ligand; TMB, tumor mutation burden; ORR, include complete and partial response; DCR, include complete and partial response and stable disease; BOR, best overall response; CR, complete response; PR, partial response; SD, stable disease; PD, progression disease; CI, confidence interval.

Table 5. Treatment-related adverse events occurring in ≥1% of patients.

Hematological toxicity	All n (%), 80 (76.9)		≥3 Grade 24 (22.0)
	Any grade n (%)	Grade 1–2 n (%)	Grade 3–4 n (%)	Grade 5 n (%)
WBC count decreased	38 (36.5)	35 (33.6)	3 (2.9)	0 (0)
Neutropenia	38 (36.5)	32 (32.8)	6 (5.7)	0 (0)
Anemia	31 (29.8)	28 (26.9)	3 (2.9)	0 (0)
Thrombocytopenia	44 (42.3)	38 (36.5)	6 (5.8)	0 (0)
ALT	33 (31.7)	32 (30.7)	1 (1.0)	0 (0)
AST	35 (33.7)	33 (31.7)	2 (2.0)	0 (0)
Alkaline phosphatase	15 (14.4)	14 (13.4)	1 (1.0)	0 (0)
Bilirubin	14 (9.6)	8 (7.7)	2 (1.9)	0 (0)
Creatinine	3 (2.9)	3 (2.9)	0 (0)	0 (0)
Immune -related AEs	All n (%), 23 (22.1)		≥3 Grade 9 (8.7)
Hyperthyroidism	5 (4.8)	5 (4.8)	0 (0)	0 (0)
Hypothyroidism	4 (3.9)	4 (3.9)	0 (0)	0 (0)
Pneumonitis	1 (1.0)	1 (1.0)	0 (0)	0 (0)
Myocarditis	3 (2.9)	0 (0)	3 (2.9)	0 (0)
Hepatitis	5 (4.8)	3 (2.9)	2 (1.9)	0 (0)
Oral mucositis	3 (2.9)	2 (1.9)	1 (1.0)	0 (0)
Herpes	2 (1.9)	0 (0)	2 (1.9)	0 (0)
Rash	5 (4.8)	5 (4.8)	0 (0)	0 (0)
Jaundice	1 (1.0)	0 (0)	0 (0)	1 (1.0)
Pigmentation	1 (1.0)	1 (1.0)	0 (0)	0 (0)

Abbreviations: WBC, white blood cell; AST, aspartate aminotransferase; ALT, alanine aminotransferase; AEs, adverse events.