Nivolumab in unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma

Figures & data

Table 1. Results of phase III clinical trials evaluating immune checkpoint inhibitors in patients with esophageal cancer.

Agent (trial)	Line	Anatomic location	Histology	Patients, n	Regimen	Response rate (%)	Median PFS, months	Median OS, months	Ref.
Metastatic or recurrent setting
Nivolumab(ATTRACTION-3)	2	E	SCC	419	Nivolumab	19.0	1.7	10.9	[45]
					PTX / DTX	22.0	3.4	8.4
Pembrolizumab(KEYNOTE-181)	2	E/EGJ	SCC/AC (SCC: 63%)	628	(All patients)				[46]
					Pembrolizumab	13.1	2.1	7.1
					PTX /DTX / CPT-11	6.7	3.4	7.1
					(CPS ≥10)
					Pembrolizumab	21.5	2.6	9.3
					PTX / DTX / CPT-11	6.1	3.0	6.7
					(SCC)
					Pembrolizumab	16.7	2.2	8.2
					PTX / DTX / CPT-11	7.4	3.1	7.1
Camrelizumab(ESCORT)	2	E	SCC	457	Camrelizumab	20.2	1.9	8.3	[47]
					DTX/ CPT-11	6.4	1.9	6.2
Tislelizumab(RATIONALE-302)	2	E	SCC	512	Tislelizumab	20.3	–	8.6	[48]
					PTX / DTX / CPT-11	9.8	–	6.3
Nivolumab(CheckMate-648)	1	E	SCC	970	(PD-L1 ≥1%)				[38]
					CF + nivolumab	53.0	6.9	15.4
					Nivolumab + ipilimumab	35.0	4.0	13.7
					CF	20.0	4.4	9.1
Pembrolizumab(KEYNOTE-590)	1	E/EGJ	SCC/AC (SCC: 73%)	749	(All patients)				[40]
					CF + pembrolizumab	45.0	6.3	12.4
					CF	29.3	5.8	9.8
					(CPS ≥10)
					CF + pembrolizumab	51.1	7.5	13.5
					CF	26.9	5.5	9.4
					(ESCC)
					CF + pembrolizumab	43.8	6.3	12.6
					CF	31.0	5.8	9.8
Camrelizumab(ESCORT-1st)	1	E	SCC	596	(All patients)				[41]
					Camrelizumab + PC	72.1	6.9	15.3
					PC	62.1	5.8	12.0
					(PD-L1 ≥1%)
					Camrelizumab + PC	74.1	6.9	15.3
					PC	65.6	5.6	11.5
Toripalimab(JUPITER-6)	1	E	SCC	514	(All patients)				[42]
					Toripalimab + PC	69.3	5.7	17.0
					PC	52.1	5.5	11.0
					(PD-L1 ≥1%)
					Toripalimab + PC	–	5.7	15.2
					PC	–	5.5	10.9
Sintilimab(ORIENT-15)	1	E	SCC	659	(All patients)				[43]
					Sintilimab + PC / CF	66.1	7.2	16.7
					PC or CF	45.5	5.7	12.5
					(CPS ≥10)
					Sintilimab + PC / CF	67.6	8.3	17.2
					PC or CF	48.7	6.4	13.6
Tislelizumab(RATIONALE-306)	1	E	SCC	649	(All patients)				[43]
					Tislelizumab + doublet chemotherapy	63.5	7.3	17.2
					doublet chemotherapy	42.4	5.6	10.6
					(PD L1 TAP score ≥10%)
					Tislelizumab + doublet chemotherapy	73.3	8.3	16.6
					doublet chemotherapy	40.2	5.6	10.0
Resectable, locally advanced setting
Nivolumab(CheckMate-577)	Adjuvant	E/EGJ	SCC/AC (SCC: 29%)	794	Nivolumab	–	22.4^†	NE	[39]
					Placebo	–	11.0^†	NE

† Disease-free survival.

AC: Adenocarcinoma; CF: Cisplatin and 5-fluorouracil; CPS: Combined positive score; DTX: Docetaxel; E: Esophagus; EGJ: Esophagogastric junction; ESCC: Esophageal squamous cell carcinoma; PC: Paclitaxel plus carboplatin; PTX: Paclitaxel; SCC: Squamous cell carcinoma; TAP: Tumor area positivity.

Table 2. Adverse events in pivotal trials of nivolumab for esophageal squamous cell carcinoma.

Adverse event	ATTRACTION-1		ATTRACTION-3		CheckMate 648				CheckMate 577
	NIVO (n = 65)		NIVO (n = 209)		Chemo + NIVO (n = 310)		NIVO + IPI (n = 322)		Adjuvant NIVO (n = 532)
	Any grade	Grade ≥3	Any grade	Grade ≥3	Any grade	Grade ≥3	Any grade	Grade ≥3	Any grade	Grade ≥3
Diarrhea	9 (14)	0 (0)	22 (11)	2 (1)	60 (19)	3 (1)	32 (10)	2 (19)	88 (17)	2 (<1)
Nausea			4 (2)	0 (0)	182 (59)	11 (4)	26 (8)	1 (<1)	47 (9)	0
Decreased appetite	6 (9)	2 (3)	16 (8)	2 (1)	132 (43)	13 (4)	19 (6)	5 (2)	26 (5)	0
Constipation	1 (2)	0	–	–	59 (19)	2 (1)	7 (2)	1 (<1)	–	–
Fatigue	5 (8)	1 (2)	15 (7)	1 (<1)	61 (20)	7 (2)	29 (9)	4 (1)	90 (17)	6 (1)
Rash	5 (8)	0	23 (11)	1 (<1)	24 (8)	1 (<1)	55 (17)	7 (2)	52 (10)	4 (<1)
Interstitial lung disease	3 (5)	1 (2)	–	–	18 (6)^†	2 (<1)^†	26 (8)^†	9 (3)^†	–	4 (<1)
Hepatic function abnormal	2 (3)	1 (2)	–	–	32 (10)^‡	7 (2)^‡	42 (13)^‡	14 (4)^‡	29 (5)	2 (<1)
Hypothyroidism	–	–	–	–	18 (6)	0	43 (13)	0	50 (9)	0
Anemia	–	–	5 (2)	4 (2)	93 (30)	30 (10)	12 (4)	2 (1)	–	–
Events leading to discontinuation	7 (11)		18 (9)	8 (4)	106 (34)	29 (9)	57 (18)	41 (13)	48 (9)	26 (5)
Events leading to deaths	0		2 (1)		–	5 (2)	–	8 (2)	–	1 (<1)

† Treatment-related pulmonary adverse event.

‡ Treatment-related hepatic adverse event.

Chemo: Chemotherapy; IPI: Ipilimumab; NIVO: Nivolumab.

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