Real-World Ramucirumab and Immune Checkpoint Inhibitor Sequences in US Patients with Advanced Gastroesophageal Cancer

Figures & data

Table 1. Demographics and baseline clinical characteristics.

Characteristic	RAM then ICI, N = 148	ICI then RAM, N = 50	RAM with ICI, N = 19	RAM without ICI, N = 900
Age at 1L initiation, year, mean (SD)	62.7 (11.3)	65.0 (10.2)	58.1 (15.5)	63.3 (11.1)
Age group at 1L initiation, year, n (%)
<65	81 (54.7)	21 (42.0)	13 (68.4)	462 (51.3)
≥65	67 (45.3)	29 (58.0)	6 (31.6)	438 (48.7)
Age at RAM initiation, year, mean (SD)	63.3 (11.4)	66.3 (10.2)	58.9 (14.9)	64.1 (11.1)
Age group at RAM initiation, year, n (%)
<65	76 (51.4)	19 (38.0)	13 (68.4)	442 (49.1)
≥65	72 (48.7)	31 (62.0)	6 (31.6)	458 (50.9)
Gender, n (%)
Male	115 (77.7)	35 (70.0)	13 (68.4)	674 (74.9)
Female	33 (22.3)	15 (30.0)	6 (31.6)	226 (25.1)
Race, n (%)
White	90 (60.8)	37 (74.0)	10 (52.6)	600 (66.7)
Black/African–American	12 (8.1)	≤5	≤5	53 (5.9)
Asian	8 (5.4)	≤5	≤5	42 (4.7)
Other	24 (16.2)	6 (12.0)	≤5	128 (14.2)
Missing/Unknown	14 (9.5)	≤5	≤5	72 (8.0)
Geographic region, n (%)
South	61 (41.2)	17 (34.0)	9 (47.4)	307 (34.1)
Northeast	31 (21.0)	11 (22.0)	≤5	185 (20.6)
West	24 (16.2)	12 (24.0)	≤5	155 (17.2)
Midwest	16 (10.8)	6 (12.0)	≤5	126 (14.0)
Missing	16 (10.8)	≤5	≤5	127 (14.1)
Practice setting, n (%)
Community	138 (93.2)	47 (94.0)	16 (84.2)	822 (91.3)
Academic	10 (6.8)	3 (6.0)	3 (15.8)	78 (8.7)
Primary tumor site, n (%)
Gastric	58 (39.2)	16 (32.0)	9 (47.4)	365 (40.6)
GEJ	43 (29.1)	17 (34.0)	4 (21.1)	264 (29.3)
Esophageal	47 (31.8)	17 (34.0)	6 (31.6)	271 (30.1)
Histology, n (%)
Adenocarcinoma	141 (95.3)	46 (92.0)	17 (89.5)	874 (97.1)
SCC	4 (2.7)	4 (8.0)	2 (10.5)	12 (1.3)
Other	2 (1.4)	0	0	10 (1.1)
Adenosquamous	1 (0.7)	0	0	2 (0.2)
Unknown/Not documented	0	0	0	2 (0.2)
Time between any 1L start and last activity/death, months, median (IQR)	16.1 (11.8–25.2)	19.5 (11.7–27.4)	11.2 (5.4–25.2)	12.4 (7.5–19.6)
Time between RAM 1L start and last activity/death, months, median (IQR)	8.8 (5.3–15.1)	4.2 (1.3–8.2)	4.9 (2.5–10.3)	3.6 (1.7–7.4)
Stage at initial diagnosis, n (%)
I	3 (2.0)	1 (2.0)	0	20 (2.2)
II	11 (7.4)	10 (20.0)	3 (15.8)	86 (9.6)
III	26 (17.6)	5 (10.0)	3 (15.8)	164 (18.2)
IV	98 (66.2)	31 (62.0)	10 (52.6)	551 (61.2)
Unknown	10 (6.8)	3 (6.0)	3 (15.8)	79 (8.8)
Criterion for advanced diagnosis, n (%)
Stage IV/IVB	97 (65.5)	31 (62.0)	10 (52.6)	548 (60.9)
Locoregional or distant recurrence	25 (16.9)	9 (18.0)	4 (21.1)	174 (19.3)
Surgery not received – Due to any reason	19 (12.8)	10 (20.0)	5 (26.3)	149 (16.6)
Incomplete resection	7 (4.7)	0	0	29 (3.2)
HER2 status at RAM initiation, n (%)
Positive	24 (16.2)	11 (22.0)	5 (26.3)	165 (18.3)
Negative	113 (76.4)	29 (58.0)	12 (63.2)	618 (68.7)
Equivocal	1 (0.7)	1 (2.0)	0	10 (1.1)
Unknown/No evidence missing	10 (6.8)	9 (18.0)	2 (10.5)	107 (11.9)

1L: First-line; ECOG: Eastern Cooperative Oncology Group; ICI: Immune checkpoint inhibitor; GEJ: Gastroesophageal junction; ICI: Immune checkpoint inhibitor; IQR: Interquartile range; n: Number of patients with observed results; N: Number of patients in the group; RAM: Ramucirumab; SCC: Squamous-cell carcinoma; SD: Standard deviation.

Table 2. Baseline Clinical and Treatment Characteristics.

Characteristic	RAM then ICI, N = 148	ICI then RAM, N = 50	RAM with ICI, N = 19	RAM without ICI, N = 900
ECOG PS at 1L initiation, n (%)
0	41 (27.7)	10 (20.0)	2 (10.5)	184 (20.4)
1	57 (38.5)	21 (42.0)	5 (26.3)	310 (34.4)
2	9 (6.1)	5 (10.0)	4 (21.1)	102 (11.3)
3+	5 (3.4)	1 (2.0)	2 (10.5)	24 (2.7)
Unknown	36 (24.3)	13 (26.0)	6 (31.6)	280 (31.1)
ECOG PS at RAM initiation, n (%)
0	30 (20.3)	9 (18.0)	1 (5.3)	122 (13.6)
1	63 (42.6)	18 (36.0)	5 (26.3)	299 (33.2)
2	17 (11.5)	15 (30.0)	4 (21.1)	182 (20.2)
3+	5 (3.4)	2 (4.0)	4 (21.1)	68 (7.6)
Unknown	33 (22.3)	6 (12.0)	5 (26.3)	229 (25.4)
RAM in Line of therapy, n (%)
1L	19 (12.8)	0	8 (42.1)	132 (14.7)
2L	91 (61.5)	3 (6.0)	5 (26.3)	476 (52.9)
3L	25 (16.9)	24 (48.0)	2 (10.5)	206 (22.9)
4L+	13 (8.8)	23 (46.0)	4 (21.1)	86 (9.6)
Maximum number of lines of therapy, n (%)
1	0	0	6 (31.6)	100 (11.1)
2	11 (7.4)	3 (6.0)	5 (26.3)	337 (37.4)
3	48 (32.4)	20 (40.0)	4 (21.1)	284 (31.6)
4	47 (31.8)	10 (20.0)	1 (5.3)	101 (11.2)
5	30 (20.3)	10 (20.0)	0	53 (5.9)
6	12 (8.1)	7 (14.0)	3 (15.8)	25 (2.8)
RAM Regimens, n (%)
RAM + PAC	123 (83.1)	36 (72.0)	0	645 (71.7)
RAM monotherapy	10 (6.8)	6 (12.0)	0	174 (19.3)
RAM + Other therapy	15 (10.1)	8 (16.0)	19 (100)	81 (9.0)
Year of 1L initiation, n (%)
2011	0	0	0	4 (0.4)
2012	3 (2.0)	0	0	16 (1.8)
2013	2 (1.4)	0	0	70 (7.8)
2014	11 (7.4)	3 (6.0)	0	140 (15.6)
2015	20 (13.5)	4 (8.0)	4 (21.1)	175 (19.4)
2016	30 (20.3)	8 (16.0)	2 (10.5)	149 (16.6)
2017	38 (25.7)	10 (20.0)	2 (10.5)	123 (13.7)
2018	23 (15.5)	15 (30.0)	5 (26.3)	113 (12.6)
2019	20 (13.5)	9 (18.0)	6 (31.6)	101 (11.2)
2020	1 (0.7)	1 (2.0)	0	9 (1.0)
Time from 1L to RAM initiation in months, median (IQR)	6.2 (3.0–10.6)	12.2 (8.9–19.4)	3.3 (0.0–13.2)	7.2 (3.4–12.5)

1L: First-line therapy, ECOG PS: Eastern Cooperative Oncology Group Performance Status, ICI: Immune checkpoint inhibitor; IQR: Interquartile range; L: Line of therapy; n: Number of patients with observed results; N: Number of patients in the group; PAC: Paclitaxel; RAM: Ramucirumab.

Figure 1. Treatment Regimens in Any Line of Therapy – RAM then ICI Group.

Regimens may include HER2-targeted therapies (e.g., trastuzumab), which are not presented here. Regimen of HER2-targeted monotherapy is included in ‘Other’.

FOLFIRI: Chemotherapy regimen consisting of leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan; LOT: Line of therapy; N: Number of patients in each line of therapy; n: number of patients in eachline of therapy; TAS-102: Trifluridine/tripiracil.

Table 3. Most common regimens in each line of therapy – RAM then ICI group.

Line of therapy and Regimen	RAM then ICI, N = 148
1L, n (%)	148 (100.0)
FOLFOX	43 (29.1)
Carboplatin + PAC	14 (9.5)
PAC + RAM	13 (8.8)
Capecitabine + epirubicin + oxaliplatin	7 (4.7)
FOLFOX + trastuzumab	7 (4.7)
2L, n (%)	148 (100.0)
PAC + RAM	68 (46.0)
FOLFOX	14 (9.5)
Pembrolizumab	8 (5.4)
Nivolumab	5 (3.4)
FOLFIRI	5 (3.4)
3L, n (%)	137 (92.6)
Pembrolizumab	44 (32.1)
PAC + RAM	19 (13.9)
FOLFIRI	18 (13.1)
Nivolumab	17 (12.4)
Irinotecan	5 (3.7)
4L, n (%)	89 (60.1)
Pembrolizumab	25 (28.1)
Nivolumab	12 (13.5)
FOLFIRI	9 (10.1)
PAC + RAM	8 (9.0)
Irinotecan	5 (5.6)
5L, n (%)	42 (28.4)
Pembrolizumab	20 (47.6)
Nivolumab	3 (7.1)
FOLFOX	2 (4.8)
RAM	1 (2.4)
PAC + RAM + trastuzumab	1 (2.4)

All data are presented as n (%).

1L: First-line therapy, 2L: Second-line therapy, 3L: Third-line therapy, 4L: Fourth-line therapy, 5L: Fifth-line therapy, FOLFIRI: Folinic acid, 5-fluorouracil, and irinotecan; FOLFOX: Folinic acid, 5-fluorouracil, and oxaliplatin; ICI: Immune checkpoint inhibitor; n: Number of patients with observed results; N: Number of patients in the group; PAC: Paclitaxel; RAM: Ramucirumab.

There may be additional regimens with the same minimum number of patients which are not presented here.

Figure 2. Treatment Regimens in Any Line of Therapy – ICI then RAM Group.

Regimens may include HER2-targeted therapies (eg, trastuzumab), which are not presented here.

FOLFIRI: Chemotherapy regimen consisting of leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan; LOT: Line of therapy; N: Number of patients in each line of therapy; TAS-102: Trifluridine/tripiracil.

Table 4. Most common regimens in each line of therapy – ICI then RAM group.

Line of therapy and Regimen	ICI then RAM, N = 50
1L, n (%)	50 (100.0)
FOLFOX	19 (38.0)
Carboplatin + PAC	7 (14.0)
FOLFOX + trastuzumab	6 (12.0)
Fluorouracil + docetaxel + leucovorin + oxaliplatin	4 (8.0)
Pembrolizumab	3 (6.0)
2L, n (%)	50 (100.0)
Pembrolizumab	19 (38.0)
Nivolumab	7 (14.0)
FOLFOX	4 (8.0)
FOLFIRI	3 (6.0)
Carboplatin + PAC	3 (6.0)
3L, n (%)	47 (94.0)
PAC + RAM	18 (38.3)
Pembrolizumab	11 (23.4)
FOLFIRI	3 (6.4)
Trifluridine/tipiracil	2 (4.3)
Nivolumab	2 (4.3)
4L, n (%)	27 (54.0)
PAC + RAM	8 (29.6)
Pembrolizumab	4 (14.8)
RAM	3 (11.1)
FOLFIRI	2 (7.4)
PAC + pembrolizumab + RAM	1 (3.7)
5L, n (%)	17 (34.0)
PAC + RAM	8 (47.1)
FOLFOX	2 (11.8)
Irinotecan	1 (5.9)
Pembrolizumab	1 (5.9)
Docetaxel + irinotecan + RAM	1 (5.9)

All data are presented as n (%).

1L: First-line therapy, 2L: Second-line therapy, 3L: Third-line therapy, 4L: Fourth-line therapy, 5L: Fifth-line therapy, FOLFIRI: Folinic acid, 5-fluorouracil, and irinotecan; FOLFOX: Folinic acid, 5-fluorouracil, and oxaliplatin; ICI: Immune checkpoint inhibitor; n: Number of patients with observed results; N: Number of patients in the group; PAC: Paclitaxel; RAM: Ramucirumab.

There may be additional regimens with the same minimum number of patients which are not presented here.

Table 5. Most common regimens in each line of therapy – RAM with ICI.

Line of therapy and Regimen	RAM with ICI, N = 19
1L, n (%)	19 (100.0)
FOLFOX	3 (15.8)
Cisplatin + PAC + pembrolizumab + RAM	2 (10.5)
PAC + pembrolizumab + RAM	2 (10.5)
Carboplatin + PAC	2 (10.5)
Pembrolizumab + RAM	2 (10.5)
2L, n (%)	13 (68.4)
PAC + pembrolizumab + RAM	4 (30.8)
Docetaxel + irinotecan + pembrolizumab + RAM	1 (7.7)
CAPEOX	1 (7.7)
Atezolizumab + pembrolizumab + RAM + trastuzumab	1 (7.7)
Fluorouracil + cisplatin + docetaxel + oxaliplatin	1 (7.7)
3L, n (%)	8 (42.1)
Irinotecan	1 (12.5)
Fluorouracil + carboplatin + PAC-protein-bound	1 (12.5)
Docetaxel + pembrolizumab + RAM	1 (12.5)
PAC + pembrolizumab + trastuzumab	1 (12.5)
Irinotecan + pembrolizumab + RAM	1 (12.5)
4L^†, n (%)	4 (21.1)
Capecitabine	1 (25.0)
Nivolumab + RAM	1 (25.0)
PAC + pembrolizumab + RAM	1 (25.0)
Capecitabine + PAC-protein-bound	1 (25.0)
5L^†, n (%)	3 (15.8)
CAPEOX + trastuzumab	1 (33.3)
PAC-protein bound + pembrolizumab + RAM	1 (33.3)
FOLFIRI	1 (33.3)

† All regimens for 4L and 5 therapies presented in table.

All data are presented as n (%).

1L: First-line therapy, 2L: Second-line therapy, 3L: Third-line therapy, 4L: Fourth-line therapy, 5L: Fifth-line therapy, CAPEOX: Capecitabine and oxaliplatin; FOLFIRI: Folinic acid, 5-fluorouracil, and irinotecan; FOLFOX: Folinic acid, 5-fluorouracil, and oxaliplatin; ICI: Immune checkpoint inhibitor; n: Number of patients with observed results; N: Number of patients in the group; PAC: Paclitaxel; RAM: Ramucirumab.

There may be additional regimens with the same minimum number of patients which are not presented here.

Table 6. Median time on RAM therapy (months) - RAM + PAC and RAM monotherapy.

Therapy	RAM then ICI, N = 148	ICI then RAM, N = 50	RAM without ICI, N = 900
RAM + PAC
2L, n (IQR)	3.0 (1.7–5.1)	NA	2.3 (1.1–5.0)
3L, n (IQR)	2.8 (1.4–5.2)	1.9 (0.5–5.8)	2.3 (1.4–4.2)
RAM monotherapy
2L, n (IQR)	2.8 (2.3–4.6)	^†	2.3 (1.1–5.2)
3L, n (IQR)	1.9 (1.4–2.5)	1.3 (0.5–2.0)	1.4 (0.5–2.8)

† No 2L RAM monotherapy.

Data are presented median (IQR), month, based on Kaplan–Meier estimates, unless specified.

2L: 2nd line; 3L: 3rd line; ICI: Immune checkpoint inhibitor; IQR: Interquartile range; n: Number of patients with observed results; N: Number of patients in the group; NA: Not estimable; PAC: Paclitaxel; RAM: Ramucirumab.

The table excluded RAM + ICI in same line group.