HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma

Figures & data

Table 1 Baseline demographic and clinical characteristics

Characteristics	Total (N=81)
Median age (Q1–Q3), years	60 (52–69)
Male, n (%)	54 (66.7)
Prior nephrectomy, n (%)	68 (83.9)
Metastatic at diagnosis, n (%)	28 (34.6)
Stage, n (%)
III	4 (4.9)
IV	71 (87.6)
ECOG PS, n (%)
0	6 (7.4)
1	62 (76.5)
≥2	13 (16.0)
MSKCC risk group, n (%)
Favorable (0 risk factor)	15 (18.5)
Intermediate (1–2 risk factors)	47 (58.0)
Poor (≥3 risk factors)	10 (12.3)
Number of metastatic sites, n (%)
1	29 (35.8)
2	23 (28.4)
≥3	29 (35.7)
Site of metastases, n (%)
Lung	63 (77.8)
Lymph nodes	32 (39.5)
Bone	19 (23.5)
Liver	14 (17.3)
Brain	4 (4.9)

Notes: Data are expressed as n (%). Missing data: MSKCC (n=9). Risk factors are low serum hemoglobin level, elevated corrected serum calcium level, elevated serum lactate dehydrogenase level, a poor performance status (ECOG ≥2 or Karnosfky >80%) and an interval of <1 year between diagnosis and treatment.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; MSKCC, Memorial Sloan-Kettering Cancer Center.

Table 2 Baseline characteristics by c-Myc expression

Characteristics	Negative c-Myc (n=41)	Positive c-Myc (n=19)	P-value
Metastatic at diagnosis	11 (26.8)	19 (31.6)	0.2367
Prior nephrectomy, n (%)	36 (87.8)	19 (100)	0.1684
ECOG PS, n (%)
0	3 (7.4)	1 (5.3)	1.000
1	32 (78.1)	16 (84.2)
≥2	6 (14.7)	2 (10.5)
MSKCC risk group, n (%)
Favorable (0 risk factor)	10 (24.4)	2 (10.5)	0.3474
Intermediate (1–2 risk factors)	21 (51.2)	14 (73.7)
Poor (≥3 risk factors)	6 (14.6)	2 (10.5)
Not evaluable	4 (9.8)	1 (5.3)
Number of metastatic sites, n (%)
1	14 (34.2)	20 (33.3)	0.7688
2	11 (26.8)	16 (26.7)
≥3	16 (39.0)	24 (40.0)
Site of metastases, n (%)
Lung	35 (85.3)	14 (73.6)	0.3007
Bone	9 (21.9)	4 (21.0)	1.000
Liver	6 (14.6)	4 (21.0)	0.7111
Brain	3 (7.3)	1 (5.2)	1.0000

Notes: Data are expressed as n (%). Missing data: MSKCC (n=9). Risk factors are low serum hemoglobin level, elevated corrected serum calcium level, elevated serum lactate dehydrogenase level, a poor performance status (ECOG ≥2 or Karnosfky >80%) and an interval of <1 year between diagnosis and treatment.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; MSKCC, Memorial Sloan-Kettering Cancer Center.

Table 3 Baseline characteristics by c-Myc expression and HIF-2α

Characteristics	Negative c-Myc or HIF-2α (n=55)	Positive c-Myc and HIF-2α (n=5)	P-value
Metastatic at diagnosis	15 (27.3)	4 (80.0)	0.0312
Prior nephrectomy, n (%)	50 (90.9)	5 (100)	1.0000
ECOG PS, n (%)
0	3 (5.5)	1 (20.0)	0.2946
1	45 (81.8)	3 (60.0)
≥2	7 (12.7)	1 (20.0)
MSKCC risk group, n (%)
Favorable (0 risk factor)	12 (21.8)	0 (0.0)	0.1531
Intermediate (1–2 risk factors)	32 (58.2)	3 (60.0)
Poor (≥3 risk factors)	6 (10.9)	2 (40.0)
Not evaluable	5 (9.1)	0 (0.0)
Number of metastatic sites, n (%)
1	17 (30.9)	3 (60.0)	0.5486
2	16 (29.19	0 (0.0)
≥3	22 (40.01)	2 (40.0)
Site of metastases, n (%)
Lung	45 (81.8)	4 (80.0)	1.0000
Bone	11 (20.0)	2 (40.0)	0.2946
Liver	9 (16.4)	1 (20.0)	1.0000
Brain	4 (7.3)	0 (0.0)	1.0000

Notes: Data are expressed as n (%). Missing data: MSKCC (n=9). Risk factors are low serum hemoglobin level, elevated corrected serum calcium level, elevated serum lactate dehydrogenase level, a poor performance status (ECOG ≥2 or Karnosfky >80%) and an interval of <1 year between diagnosis and treatment.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; HIF, hypoxia-inducible factor; MSKCC, Memorial Sloan-Kettering Cancer Center.

Figure 1 Kaplan–Meier estimates.

Notes: All patients PFS (A) and PFS according to MSKCC risk (B).
Abbreviations: MSKCC, Memorial Sloan-Kettering Cancer Center; NA, not applicable; PFS, progression-free survival.

Table 4 Baseline characteristics of patients with complete remission

Characteristics	Total (n=6)
Median age (SD), years	50.2 (9.6)
Metastatic at diagnosis, n (%)	2 (33.3)
Stage, n (%)
III	1 (16.7)
IV	5 (83.3)
ECOG PS, n (%)
0	2 (33.3)
1	4 (66.6)
MSKCC risk group, n (%)
Favorable (0 risk factor)	1 (16.7)
Intermediate (1–2 risk factors)	3 (50.0)
Not evaluable	2 (33.3)
Number of metastatic sites, n (%)
1	3 (50.0)
2	2 (33.3)
≥3	1 (16.7)
Site of metastases, n (%)
Lung	6 (100)
Lymph nodes	3 (50.0)
Bone	0 (0.0)
Liver	0 (0.0)
Brain	0 (0.0)
Kidney	1 (16.7)

Notes: Data are expressed as n (%). Missing data: MSKCC (n=9). Risk factors are low serum hemoglobin level, elevated corrected serum calcium level, elevated serum lactate dehydrogenase level, a poor performance status (ECOG ≥2 or Karnosfky >80%) and an interval of <1 year between diagnosis and treatment.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; MSKCC, Memorial Sloan-Kettering Cancer Center.

Figure 2 Examples of immunohistochemistry.

Notes: (A) c-Myc-positive staining; (B) c-Myc-negative staining; (C) HIF-1α-positive staining; (D) HIF-1α-negative staining; (E) HIF-2α-negative staining; (F) HIF-2α-positive staining. Magnification (A and E) 400×; (B, C, D and F) 100×.
Abbreviation: HIF, hypoxia-inducible factor.

Figure 3 Kaplan–Meier estimates according to c-Myc.

Notes: (A) PFS according to c-Myc expression; (B) PFS according to c-Myc and MSKCC risk group; (C) PFS according to c-Myc and HIF-2α expression.
Abbreviations: HIF, hypoxia-inducible factor; MSKCC, Memorial Sloan-Kettering Cancer Center; PFS, progression-free survival.