The safety of current treatment options for advanced esophageal cancer after first-line chemotherapy

Figures & data

Table 1. Main outcomes and adverse events in the ATTRACTION-1 trial

	ATTRACTION-1
Efficacy
Number of patients	65
ORR (%)	17
Median PFS (months)	1.5
Median OS (months)	10.8
Treatment-related AEs	n (%)
	Any grade (N = 55)	Grade ≥3 (N = 55)
Diarrhea	9 (14)	0 (0)
Decreased appetite	6 (9)	2 (3)
Constipation	1 (2)	0 (0)
Fatigue	5 (8)	1 (2)
Rash	5 (8)	0 (0)
Elevated blood creatinine phosphokinase level	3 (5)	2 (3)
Dehydration	2 (3)	2 (3)
Pneumonia	1 (2)	0 (0)
Lung infection	4 (6)	2 (3)
Interstitial lung disease	3 (5)	1 (2)
Hyponatremia	1 (2)	1 (2)
Hyperkalemia	0 (0)	0 (0)
Abnormal hepatic function	2 (3)	1 (2)
Bile duct stenosis	0 (0)	0 (0)
Decreased neutrophil count	1 (1)	1 (2)
Events leading to discontinuation	7 (11)
Events leading to death	0 (0)

Abbreviations: ORR, objective response rate; PFS, progression-free survival; OS, overall survival; AE, adverse event

Table 2. Main outcomes and treatment-related adverse events in the ATTRACTION-3 trial

	ATTRACTION-3
Efficacy	Nivolumab		Chemotherapy
Number of patients	210		209
ORR (%)	19		22
Median PFS (months)	1.7		3.4
Median OS (months)	10.9		8.4
Treatment-related AEs	N = 209 (100)		N = 208 (100)
	Any grade	Grade ≥3	Any grade	Grade ≥3
Anemia	5 (2)	4 (2)	49 (24)	19 (9)
Decreased white blood cell count	2 (1)	1 (<1)	72 (35)	46 (22)
Decreased neutrophil count	3 (1)	1 (<1)	76 (37)	59 (28)
Neutropenia	1 (<1)	0 (0)	40 (19)	29 (14)
Febrile neutropenia	0 (0)	0 (0)	22 (11)	22 (11)
Diarrhea	22 (11)	2 (1)	20 (10)	2 (1)
Nausea	4 (2)	0 (0)	34 (16)	1 (<1)
Stomatitis	5 (2)	1 (<1)	25 (12)	1 (<1)
Decreased appetite	16 (8)	2 (1)	56 (27)	10 (5)
Fatigue	15 (7)	1 (<1)	43 (21)	9 (4)
Alopecia	3 (1)	0 (0)	98 (47)	0 (0)
Arthralgia	3 (1)	0 (0)	21 (10)	1 (<1)
Peripheral sensory neuropathy	1 (<1)	0 (0)	47 (23)	1 (<1)
Rash	23 (11)	1 (<1)	31 (15)	2 (1)
Serious events	33 (16)	20 (10)	47 (23)	41 (20)
Events leading to death	2 (1)	2 (1)	3 (1)	3 (1)
Events leading to discontinuation	18 (9)	8 (4)	19 (9)	13 (6)

Abbreviations: ORR, objective response rate; PFS, progression-free survival; OS, overall survival; AE, adverse event

Table 3. Main outcomes and adverse events in the KEYNOTE-180 trial

	KEYNOTE-180
	Pembrolizumab
Number of patients	121
	ORR (%)	Median PFS (months)	Median OS (months)
All patients	9.9	2.0	5.8
SCC	14.3	2.1	6.8
AC	5.2	1.9	3.9
CPS≥10	13.8	2.0	6.3
CPS<10	6.3	2.0	5.4
Treatment-related AEs	Any grade	Grade ≥3
Any	70 (57.9)	15 (12.4)
Fatigue	13 (10.7)	0 (0)
Rash	9 (7.4)	0 (0)
Pruritus	8 (6.6)	0 (0)
Hypothyroidism	7 (5.8)	0 (0)
Diarrhea	7 (5.8)	1 (0.8)
Pneumonitis	9 (7.4)	3 (2.4)
Type 1 diabetes mellitus	4 (3.3)	4 (3.3)
Led to discontinuation	5 (4.1)
Led to death	1 (0.8)

Abbreviations: ORR, objective response rate; PFS, progression-free survival; OS, overall survival; SCC, squamous cell carcinoma; AC, adenocarcinoma; CPS, combined-positive score; AE, adverse event

Table 4. Main outcomes and adverse events for the KEYNOTE-181 trial

		KEYNOTE-181
		Pembrolizumab		Chemotherapy
Number of patients		314		314
ORR (%)	All patients	13.1		6.7
	CPS≥10	21.5		6.1
	SCC	16.7		7.4
Median PFS (months)	All patients	2.1		3.4
	CPS≥10	2.6		3.0
	SCC	2.2		3.1
Median OS (months)	All patients	7.1		7.1
	CPS≥10	9.3		6.7
	SCC	8.2		7.1
AEs		N = 314 (100)		N = 296 (100)
		All grade	Grade ≥3	All grade	Grade ≥3
Anemia		8 (2.5)	4 (1.3)	66 (22.3)	23 (7.8)
White blood cell count decreased		1 (0.3)	0 (0)	49 (16.6)	30 (10.1)
Neutropenia		0 (0)	0 (0)	34 (11.5)	21 (7.1)
Diarrhea		17 (5.4)	2 (0.6)	60 (20.3)	9 (3.0)
Nausea		22 (7.0)	0 (0)	64 (21.6)	7 (2.4)
Decreased appetite		27 (8.6)	2 (0.6)	46 (15.5)	3 (1.0)
Fatigue		37 (11.8)	2 (0.6)	61 (20.6)	1 (0.3)
Alopecia		2 (0.6)	0 (0)	86 (29.1)	1 (0.3)
Peripheral sensory neuropathy		1 (0.3)	0 (0)	50 (16.9)	1 (0.3)
All events		202 (64.3)	57 (18.2)	255 (86.1)	121 (40.9)
Led to discontinuation		19 (6.1)		19 (6.4)
Led to death		5 (1.6)		5 (1.7)
Immune-mediated AEs		Pembrolizumab		Chemotherapy
Any		73 (23.2)		22 (7.4)
Hypothyroidism		36 (11.5)		7 (2.4)
Pneumonitis		15 (4.8)		2 (0.7)
Hyperthyroidism		13 (4.1)		2 (0.7)
Hepatitis		6 (1.9)		0 (0)
Colitis		3 (0.9)		2 (0.7)
Infusion-related reactions		3 (0.9)		8 (2.7)

Abbreviations: ORR, objective response rate; PFS, progression-free survival; OS, overall survival; SCC, squamous cell carcinoma; AC, adenocarcinoma; CPS, combined-positive score; AE, adverse event

Table 5. Any Grade of irAEs in four trials of anti-PD-1 antibody

	Nivo (AT-1) n=65	Nivo (AT-3) n=210	Pembro (KN-180) n=121	Pembro (KN-181) n=314
Diarrhoea	9 (13.8)	22 (10.5)	7 (5.8)	17 (5.4)
Nausea	-	4 (1.9)	-	22 (7.0)
Decreased appetite	6 (9.2)	16 (7.6)	-	27 (8.6)
Fatigue	5(7.7)	15 (7.1)	13 (10.7)	37 (11.8)
Hypothyrodism	-	2 (0.9)	7 (5.8)	36 (11.5)
Intestinal lung disease	3 (4.6)	5 (2.4)	-	-
Pneumonitis	-	4 (1.9)	9 (7.4)	15 (4.8)
Rash	5 (7.7)	23 (11.0)	9 (7.4)	-
Serious events	-	33 (15.7)	-	41 (20)
Events leading to death	0 (0)	2 (0.9)	1 (0.8)	5 (1.6)
Events leading to discontinuation	7 (10.8)	18 (8.6)	5 (4.1)	19 (6.1)

Abbreviations: Nivo, Nivolumab; Pembro, Pembrolizumab