177Lu-DOTATATE Plus Capecitabine Versus 177Lu-DOTATATE Alone in Patients with Advanced Grade 1/2 Gastroenteropancreatic Neuroendocrine Tumors (LuCAP): A Randomized, Phase 2 Trial

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FIGURE 1.
CONSORT flow diagram describing study enrollment process.
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FIGURE 2.
Waterfall plots showing radiographic responses in experimental (A) and control (B) arms. x-axis represents individual patients, and y-axis represents maximum percent change in sum of largest dimensions (SLD) from baseline. ^●Appearance of new lesions. ^#Patient died before radiographic assessment. *Nonmeasurable disease. CAP = capecitabine; Lu-TATE = ¹⁷⁷Lu-DOTATATE.
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FIGURE 3.
Forest plot for objective radiographic response across different subgroups for experimental arm versus control arm. Squares represent risk ratio (RR), and horizontal lines represent 95% CIs. CAP = capecitabine; GI-NET = gastrointestinal NET; Lu-TATE = ¹⁷⁷Lu-DOTATATE; p-NET = pancreatic NET.
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FIGURE 4.
Kaplan–Meier curves showing PFS (A) and OS (B) between 2 arms. CAP = capecitabine; Lu-TATE = ¹⁷⁷Lu-DOTATATE.

TABLE 1.

Demographic and Clinical Characteristics of Patients in the Study

Characteristic	¹⁷⁷Lu-DOTATATE plus capecitabine (n = 36)	¹⁷⁷Lu-DOTATATE alone (n = 36)	P
Age (y)	52.5 (43–60)	54.5 (37–61.8)	0.844
<60 y	27 (75)	23 (64)	0.306
≥60 y	9 (25)	13 (36)
Sex
Males	13 (36)	18 (50)	0.234
Females	23 (64)	18 (50)
Primary tumor site
Gastrointestinal NET	24 (67)	21 (58)	0.465
Stomach	4 (11)	3 (8)
Small bowel	18 (50)	14 (39)
Large bowel	2 (6)	4 (11)
Pancreatic NET	12 (33)	15 (42)
Tumor grade
Grade 1	12 (33)	16 (44)	0.334
Grade 2	24 (67)	20 (56)
Ki-67 index
<10%	25 (69)	28 (78)	0.422
≥10%	11 (31)	8 (22)
Prior treatment
Surgery	11 (31)	14 (39)	0.458
SSA	23 (64)	22 (61)	0.808
Everolimus	12 (33)	9 (25)	0.437
Sunitinib	3 (8)	1 (3)	0.614
Chemotherapy	1 (3)	4 (11)	0.357
Functional symptom(s) at baseline	3 (8)	4 (11)	1.000
Disease extent at baseline
Primary	27 (75)	23 (64)	0.306
Lymph nodes	21 (58)	24 (67)	0.216
Liver	31 (86)	27 (75)	0.234
Bones	11 (31)	12 (33)	0.800
Lungs	1 (3)	1 (3)	1.000
Others	9 (25)	7 (19)	0.571
Krenning score
3	15 (42)	12 (33)	0.465
4	21 (58)	24 (67)
¹⁸F-FDG PET status^*
Negative	18 (50)	15 (42)	0.478
Positive	18 (50)	21 (58)

↵* ¹⁸F-FDG PET status determined as positive if lesion uptake was higher than that of background.
SSA = somatostatin analog.
Qualitative data are number and percentage. Continuous data are median and IQR of first–third quartiles.

TABLE 2.

Toxicity Profile of Patients in the Study as Evaluated with CTCAE Version 5.0

	¹⁷⁷Lu-DOTATATE plus capecitabine (n = 36)		¹⁷⁷Lu-DOTATATE alone (n = 36)
Type of AE	Any grade	Grade 3/4	Any grade	Grade 3/4	P^*
Any AE	29 (81)	7 (19)	31 (86)	6 (17)	0.527
AE causing treatment discontinuation	2 (6)^†	1 (3)	2 (6)^‡	2 (6)	1.000
Symptomatic events
Nausea	19 (53)	0 (0)	18 (50)	0 (0)	0.814
Vomiting	17 (47)	0 (0)	16 (44)	0 (0)	0.813
Diarrhea	3 (8)	0 (0)	1 (3)	0 (0)	0.614
Fatigue	10 (28)	0 (0)	6 (17)	0 (0)	0.257
Weight loss	2 (6)	0 (0)	2 (6)	0 (0)	1.000
Weight gain	0 (0)	0 (0)	1 (3)	0 (0)	1.000
Pain in abdomen	7 (19)	1 (3)	10 (28)	1 (3)	0.405
Abdominal distension	6 (17)	0 (0)	0 (0)	0 (0)	0.025
Musculoskeletal pain	2 (6)	0 (0)	5 (14)	1 (3)	0.429
Decreased appetite	1 (3)	0 (0)	3 (8)	0 (0)	0.614
Hematologic and biochemical events
Anemia	13 (36)	3 (8)	14 (39)	2 (6)	0.808
Leukopenia	14 (39)	3 (8)	13 (36)	1 (3)	0.808
Thrombocytopenia	11 (31)	1 (3)	12 (33)	3 (8)	0.800
Neutropenia	5 (14)	1 (3)	2 (6)	0 (0)	0.429
Increased creatinine	3 (8)	0 (0)	8 (22)	0 (0)	0.101
Raised AST/ALT	3 (8)	0 (0)	2 (6)	0 (0)	1.000
Raised ALP	5 (14)	1 (3)	4 (11)	0 (0)	1.000
Raised serum bilirubin	3 (8)	0 (0)	0 (0)	0 (0)	0.239
Reduced serum albumin	3 (8)	0 (0)	4 (11)	0 (0)	1.000
Hypo- or hypernatremia	2 (6)	0 (0)	4 (11)	0 (0)	0.674
Hypo- or hyperkalemia	2 (6)	1 (3)	1 (3)	0 (0)	1.000

↵* P values estimated for comparisons of AEs of any grade.
↵† AEs leading to treatment discontinuation in experimental arm included persistent grade 3 cytopenias (n = 1) and grade 2 increased serum creatinine (n = 1).
↵‡ AEs leading to treatment discontinuation in control arm included persistent grade 3 cytopenias (n = 1) and grade 3 cytopenias along with grade 2 increased serum creatinine (n = 1).
CTCAE = Common Terminology Criteria for Adverse Events; AST = aspartate transaminase; ALT = alanine transaminase; ALP = alkaline phosphatase.
Qualitative data are number and percentage.