A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12)

Figures & data

Table 1. Baseline patient characteristics.

Characteristics	N = 44%)
Age(range), years	61 (52–82)
Sex
Male	43 (97.7%)
Female	1 (2.3%)
ECOG performance status
0	9 (20.5%)
1	33 (75.0%)
2	2 (4.5%)
Histologic type
Squamous-cell carcinoma	44 (100%)
Smoking
Never	5 (11.4%)
Previous	37 (84.1%)
Current	2 (4.5%)
Metastatic pattern
De novo metastatic	9 (20.5%)
Recurrent	35 (79.5%)
Previous treatment
Curative surgery	27 (61.4%)
Concurrent chemoradiation	26 (59.1%)
Number of prior chemotherapies
1	30 (68.2%)
2	14 (31.8%)
PD-L1 expression (n = 36)
TPS
<1%	30 (83.3%)
≥1%	6 (16.7%)
≥10%	33 (91.7%)
≥10%	3 (8.3%)
CPS
<1	19 (52.8%)
≥1	17 (47.2%)
<10	31 (86.1%)
≥10	5 (13.9%)

ECOG, Eastern Cooperative Oncology Group; PD-L1, programmed cell death ligand-1; TPS, tumor proportion score; CPS, combined positive score.

Figure 1. Tumor responses.

Response was assessed with Response Evaluation Criteria in Solid Tumors version 1.1 by investigators. (a) Waterfall plot of best percentage change for target lesions by RECIST v1.1 in all eligible patients. PD-L1 status determined by TPS is indicated as described (yellow/plus: positive, purple/horizontal line: negative, gray/X: not evaluated). (b) Spider plot of radiographic response. Tumor responses were measured at regular intervals and values show percent change of sum of longest diameters from the baseline measurement of each measurable tumor. Red diamond-shape indicating patients who progressed due to occurrence of new lesions. Gray diamond-shape indicating patients who exited the trial due to other reasons than disease progression. (c) Swimmer plot of treatment duration. The gray star-shape indicates the time of first response. The arrow indicates patients still on treatment. PD-L1 status determined by TPS is indicated as described (yellow/plus: positive, purple/horizontal line: negative, gray/X: not evaluated). TPS, tumor proportion score.

Figure 2. Kaplan-Meier analysis of survival.

(a) Progression-free survival. (b) Overall survival.

Table 2. Treatment efficacy.

Best response	N = 44%)
Partial response	9 (20.5%, 95% CI 8.5–32.4)
Stable disease	16 (36.4%, 95% CI 22.2–50.6)
Progressive disease	19 (43.2%, 95% CI 28.6–57.8)
Objective response rate	9 (20.5%, 95% CI 8.5–32.4)
Disease control rate	25 (56.8%, 95% CI 42.2–71.5)
Median progression free survival, months	3.2 (95% CI 1.3–6.9)
Median overall survival, months	11.2 (95% CI 7.8–17.3)
Median duration of response, months	23.4 (95% CI 4.4–30.2)

Table 3. Adverse events and treatment-related adverse events.

	Adverse events				Treatment-related adverse events
	(n = 44)				(n = 44)
	Grade 1–2	Grade3	Grade 4	Grade 5	Grade 1–2	Grade3	Grade 4	Grade 5
Overall number of patients	36 (82%)	15 (34%)	2 (5%)	1 (2%)	20 (45%)	4 (9%)	0 (0%)	1 (2%)
Dysphagia	6 (14%)	8 (18%)	0	0	0	0	0	0
Lung infection	8 (18%)	3 (7%)	0	0	0	1 (2%)	0	0
Rash maculo-papular	10 (23%)	0	0	0	9 (20%)	0	0	0
Hypothyroidism	9 (20%)	0	0	0	8 (18%)	0	0	0
Pruritus	9 (20%)	0	0	0	8 (18%)	0	0	0
Fever	5 (11%)	1 (2%)	0	0	0	1 (2%)	0	0
Fatigue	4 (9%)	1 (2%)	0	0	1 (2%)	0	0	0
Abdominal pain	5 (11%)	0	0	0	0	0	0	0
Myalgia	5 (11%)	0	0	0	3 (7%)	0	0	0
Pneumonitis	5 (11%)	0	0	0	5 (11%)	0	0	0
Anemia	3 (7%)	1 (2%)	0	0	0	0	0	0
Esophageal pain	3 (7%)	1 (2%)	0	0	0	0	0	0
Dyspnea	2 (5%)	1 (2%)	0	0	1 (2%)	0	0	0
Pneumothorax	2 (5%)	1 (2%)	0	0	0	0	0	0
Serum amylase increased	2 (5%)	1 (2%)	0	0	1 (2%)	1 (2%)	0	0
Thromboembolic event	0	1 (2%)	0	1 (2%)	0	1 (2%)	0	1 (2%)
Hypercalcemia	0	0	2 (5%)	0	0	0	0	0
Hypoxia	0	2 (5%)	0	0	0	0	0	0
Adrenal insufficiency	1 (2%)	1 (2%)	0	0	1 (2%)	0	0	0
Hyponatremia	1 (2%)	1 (2%)	0	0	0	0	0	0
Acidosis	0	1 (2%)	0	0	0	1 (2%)	0	0
Bullous dermatitis	0	1 (2%)	0	0	0	0	0	0
Hypertension	0	1 (2%)	0	0	0	0	0	0
Portal vein thrombosis	0	1 (2%)	0	0	0	0	0	0
Shingles	0	1 (2%)	0	0	0	0	0	0

Notes: Grade 1 or 2 events seen in ≥ 10% of patients are shown if there were no grade 3 or 4 events but those seen in < 10% are shown if a grade 3 or 4 event was also reported. Adverse events were classified with the Common Terminology Criteria for Adverse Events (version 5.0). Treatment-related adverse events were defined as adverse events for which a causal relation to spartalizumab could not be ruled out. Some patients had more than one event.

Figure 3. Biomarker analysis.

(a) Representative images (200×) of PD-L1 and CD20 IHC staining. (b) Kaplan-Meier plots of progression-free survival by (top) PD-L1 (TPS) 1% and (bottom) density of CD20-positive immune cell infiltration. CD20 high group defined as CD20-positive immune cell infiltration density higher than the median value. (c) (Left) Overall response rate and disease control rate with proportion of patients by best response. (Right) Overall response rate and disease control rate with proportion of patients by best response subdivided based on PD-L1 expression and CD20-positive immune cell infiltration. (d) Kaplan-Meier plot of progression-free survival of patients subdivided based on PD-L1 (TPS) 1% and density of CD20-positive immune cell infiltration density. IHC, immunohistochemistry; PD-L1, programmed cell death ligand 1; TPS, tumor proportion score.