Regorafenib combined with programmed cell death-1 inhibitor against refractory colorectal cancer and the platelet-to-lymphocyte ratio’s prediction on effectiveness

Table 1 Characteristics of the individual patients

No.	Age (yr)	Sex	ECOG PS	Primary tumor	Site of metastases	Liver metastases	RAS and BRAF mutation	Lines of treatment	Prior 5-Fu	Prior platinum	Prior irinotecan	Prior bevacizumab	Prior cetuximab	Prior regorafenib	Prior PD-1
1	56	Female	1	Sigmoid colon	Abdominal metastases	No	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
2	62	Female	3	Ascending colon	Multiple metastases	Yes	Not tested	4	Yes	Yes	Yes	Yes	No	Yes	No
3	51	Female	0	Rectum	Multiple metastases	Yes	Not tested	3	Yes	Yes	Yes	Yes	No	No	No
4	52	Female	1	Sigmoid colon	Multiple metastases	No	KRAS mutation	3	Yes	Yes	Yes	Yes	No	No	No
5	66	Female	1	Ascending colon	Multiple metastases	Yes	Not tested	4	Yes	Yes	Yes	Yes	No	Yes	No
6	57	Female	2	Sigmoid colon	Multiple metastases	No	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
7	48	Female	3	Liver curvature of the transverse colon	Multiple metastases	Yes	Not tested	3	Yes	Yes	Yes	Yes	No	No	No
8	61	Female	2	Rectum	Pelvic metastases	No	KRAS mutation	3	Yes	Yes	Yes	Yes	No	No	No
9	65	Female	1	Rectum	Ovary metastases	No	Wild-type	4	Yes	Yes	Yes	Yes	Yes	Yes	No
10	65	Female	0	Ascending colon	Lung metastases	No	Not tested	3	Yes	Yes	Yes	Yes	No	No	No
11	56	Female	2	Left half of the colon	Ovary metastases	No	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
12	27	Male	0	Sigmoid colon	Pelvic metastases	No	Wild-type	4	Yes	Yes	Yes	Yes	Yes	Yes	Yes
13	58	Male	1	Sigmoid colon	Liver metastases	Yes	Not tested	3	Yes	Yes	Yes	Yes	No	No	No
14	70	Female	1	Rectum	Lung metastases	No	Not tested	4	Yes	Yes	Yes	Yes	No	No	No
15	54	Male	1	Ascending colon	Multiple metastases	Yes	KRAS mutation	3	Yes	Yes	Yes	Yes	No	No	No
16	55	Male	1	Rectum	Multiple metastases	Yes	NRAS mutation	4	Yes	Yes	Yes	Yes	No	Yes	No
17	48	Female	0	Rectum	Multiple metastases	Yes	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
18	55	Male	1	Rectum	Multiple metastases	Yes	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
19	64	Male	2	Rectum	Multiple metastases	Yes	KRAS mutation	3	Yes	Yes	Yes	Yes	No	No	No
20	58	Female	0	Ascending colon	Multiple metastases	Yes	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
21	44	Female	2	Sigmoid colon	Multiple metastases	Yes	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
22	51	Male	1	Rectum	Multiple metastases	Yes	Not tested	4	Yes	Yes	Yes	Yes	No	Yes	No
23	56	Male	1	Rectum	Lung metastases	No	Not tested	4	Yes	Yes	Yes	Yes	No	No	No
24	61	Male	2	Rectum	Multiple metastases	Yes	Not tested	4	Yes	Yes	Yes	Yes	No	No	No
25	73	Male	0	Rectum	Multiple metastases	Yes (radiofrequency)	Wild-type	3	Yes	Yes	Yes	Yes	Yes	No	No
26	61	Male	1	Rectum	Multiple metastases	Yes	Wild-type	4	Yes	Yes	Yes	Yes	Yes	Yes	No
27	58	Male	2	Sigmoid colon	Multiple metastases	No	KRAS mutation	3	Yes	Yes	Yes	Yes	No	No	No
28	57	Female	1	Sigmoid colon	Liver metastases	Yes (hepatectomy)	KRAS mutation	3	Yes	Yes	Yes	Yes	No	No	No
29	67	Male	2	Rectum	Liver metastases	Yes	Not tested	3	Yes	Yes	Yes	Yes	No	No	No
30	61	Male	1	Sigmoid colon	Peritoneal metastasis	No	Wide-type	3	Yes	Yes	Yes	Yes	Yes	No	No

ECOG PS: Eastern Cooperative Oncology Group performance status.

Table 2 Treatments and outcomes

No.	Initial dose of regorafenib (mg)	Dose adjustment (mg)	PD-1 inhibitor used in combination	Number of treatment cycles	Best response	PFS (mo)	OS (mo)
1	120		Camrelizumab	16	SD	11.2	12.0
2	80		Tislelizumab	7	SD	5.0	7.0
3	160	160→80	Nivolumab	4	PD	3.4	Not reached
4	80		Camrelizumab	4	PD	3.4	4.0
5	80		Tislelizumab	3	SD	2.0	5.0
6	80		Toripalimab	5	SD	3.5	Not reached
7	80		Tislelizumab	7	SD	5.0	9.0
8	80		Pembrolizumab	5	PD	3.5	Not reached
9	120		Sintilimab	4	SD	2.8	Not reached
10	160	160→80	Toripalimab	8	SD	5.6	Not reached
11	80		Tislelizumab	2	SD	1.4	Not reached
12	160		Toripalimab	4	SD	2.8	Not reached
13	120		Nivolumab	6	SD	4.2	Not reached
14	80		Toripalimab	5	SD	3.5	Not reached
15	120		Sintilimab	6	SD	3.5	Not reached
16	80		Nivolumab	15	SD	10.5	Not reached
17	160	160→80	Sintilimab	4	PD	2.8	Not reached
18	80		Camrelizumab	5	PD	3.5	Not reached
19	80		Toripalimab	2	SD	1.4	Not reached
20	120		Camrelizumab	4	PD	3.4	7.0
21	80		Toripalimab	2	PD	1.4	Not reached
22	120		Camrelizumab	1	SD	0.7	12.0
23	80		Sintilimab	2	PD	1.4	10.0
24	80		Toripalimab	9	SD	6.3	11.0
25	120	120→80	Sintilimab	2	PD	1.4	Not reached
26	80		Sintilimab	3	SD	2.1	10.0
27	80		Toripalimab	6	SD	4.2	Not reached
28	120		Sintilimab	2	PD	1.4	Not reached
29	80		Sintilimab	1	PD	0.7	not reached
30	80		Sintilimab	2	PD	1.4	Not reached

OS: Overall survival; PD: Progressive disease; PFS: Progression-free survival; SD: Stable disease; PD-1: Programmed cell death-1.

Table 3 Treatment-related adverse event

Adverse event	Number of patients (n = 30), n (%)
	Any grade	Grade 1-2	Grade 3
Any event	17 (56.7)	13 (43.3)	4 (13.3)
Hand-foot syndrome	10 (33.3)	8 (26.7)	2 (6.7)
Hypertension	7 (23.3)	7 (23.3)	0
Malaise	6 (20.0)	6 (20.0)	0
Gastrointestinal reaction	5 (16.7)	5 (16.7)	0
Transaminase elevation	4 (13.3)	3 (10.0)	1 (3.3)
Diarrhea	3 (10.0)	3 (10.0)	0
Abnormal capillary proliferation	2 (6.7)	1 (3.3)	1 (3.3)
Hypothyroidism	2 (6.7)	2 (6.7)	0
Proteinuria	2 (6.7)	2 (6.7)	0
Rash	2 (6.7)	2 (6.7)	0
Thrombocytopenia	2 (6.7)	2 (6.7)	0
Anemia	1 (3.3)	1 (3.3)	0
Myocardial enzyme elevation	1 (3.3)	1 (3.3)	0
Oral mucositis	1 (3.3)	1 (3.3)	0
Leukopenia/neutropenia	0	0	0