Tumor growth rate to assess therapy response to immune-based combinations for metastatic renal cell carcinoma

Figures & data

Figure 1. Patients included in our study. Abbreviations: mRCC, metastatic renal cell carcinoma; P/A, pembrolizumab/axitinib; TKI, tyrosine kinase inhibitor; CT, computed tomography.

Table 1. Baseline patients’ features in both experimental (immune-based combination) and control (TKI) groups as well as in overall population, along with p-value for association between categorical or continuous variables and the two groups.

Characteristics	TKI group (n = 18)	ICI/TKI group (n = 15)	All the patients (n = 33)	p-value
Sex
Male	13 (72.2%)	10 (66.7%)	23 (69.7%)	1.000
Female	5 (27.8%)	5 (33.3%)	10 (30.3%)
Age
<60 years old	9 (50.0%)	3 (20.0%)	12 (36.4%)	0.145
≥60 years old	9 (50.0%)	12 (80.0%)	21 (63.6%)
Smoker	4 (22.2%)	5 (33.3%)	9 (27.3%)	0.697
Histology
ccRCC	16 (88.9%)	14 (93.3%)	30 (90.9%)	1.000
nccRCC	2 (11.1%)	1 (6.7%)	3 (9.1%)
Necrosis	8 (44.4%)	2 (13.3%)	10 (30.3%)	0.054
Sarcomatoid/Rhabdoid areas	6 (33.3%)	4 (26.7%)	10 (30.3%)	0.211
Surgery	17 (94.4%)	10 (66.7%)	27 (81.8%)	0.070
Lung metastases	10 (55.6%)	8 (53.3%)	18 (54.5%)	1.000
Bone metastases	3 (16.7%)	6 (40.0%)	9 (27.3%)	0.239
CNS metastases	0 (0.0%)	2 (13.3%)	2 (6.1%)	0.199
Liver metastases	3 (16.7%)	3 (20.0%)	6 (18.2%)	1.000
Pancreas metastases	2 (11.1%)	2 (13.3%)	4 (12.1%)	1.000
Lymph nodes	8 (44.4%)	9 (60.0%)	17 (52.5%)	0.491
Steroids	3 (16.7%)	4 (26.7%)	7 (21.2%)	0.674
IMDC risk groups
Favorable-risk	8 (44.4%)	5 (33.3%)	13 (39.4%)
Intermediate-risk	10 (55.6%)	8 (53.3%)	18 (54.5%)	0.264
Poor-risk	0 (0.0%)	2 (13.3%)	2 (6.1%)
Volume measurement
LN Baseline total volume (std.Dev)	3.0 (1.7)	3.9 (1.4)	3.4 (1.6)	0.138
LN Post-baseline total volume (std.Dev)	2.0 (2.9)	3.9 (2.2)	2.9 (2.7)	0.047
LN 2^nd Post-baseline total volume (std.Dev)	1.5 (3.0)	2.9 (3.5)	2.0 (3.2)	0.046
TGR1 (std.Dev)	−0.010 (0.026)	−0.001 (0.011)	−0.006 (0.021)	0.112
TGR2 (std.Dev)	−0.001 (0.005)	−0.008 (0.020)	−0.004 (0.014)	0.521
TGR2-TGR1 (std.Dev)	0.012 (0.027)	−0.005 (0.013)	0.005 (0.024)	0.026
TGR categories
PD	2 (11.1%)	2 (13.3%)	4 (12.1%)
Lower growth	2 (11.1%)	2 (13.3%)	4 (12.1%)	0.817
Response	12 (66.7%)	7 (46.7%)	19 (57.6%)
NC	2 (11.1%)	4 (26.7%)	6 (18.2%)
Outcomes
Best response
PR	10 (55.6%)	8 (53.3%)	18 (54.5%)
SD	6 (33.3%)	4 (26.7%)	10 (30.3%)	0.758
PD	2 (11.1%)	3 (20.0%)	5 (15.2%)
mPFS (std. Error)	26.3 (10.0)	NR (NC)	32.9 (6.4)	0.850
mOS (std. Error)	47.4 (5.9)	NR (NC)	47.4 (2.4)	0.137

Abbreviations: TKI, tyrosine-kinase inhibitor; ICI, immune checkpoint inhibitor; ccRCC, clear cell renal cell carcinoma; nccRCC, non-clear cell renal cell carcinoma; CNS, central nervous system; IMDC, International Metastatic RCC Database Consortium; std.Dev, standard deviation; TGR, tumor growth rate; PD, progressive disease; PR, partial response; SD, stable disease; mPFS, median progression-free survival; mOS, median overall survival, std.Error, standard error; LN=natural-logarithmized; NR=not reached; NC=not calculable.

Figure 2. PFS in patients in the control group, treated with a single-agent TKI. Patients were further divided in two groups: group 1 with high velocity volume reduction (HvVR) and group 2 with lower velocity volume reduction or increase (LvVR).

Figure 3. PFS in patients in the immunotherapy group, treated with pembrolizumab plus axitinib. Patients were further divided in two groups: group 1 with high velocity volume reduction (HvVR) and group 2 with lower velocity volume reduction or increase (LvVR).

Figure 4. OS in patients in the control group, treated with a single-agent TKI. Patients were further divided in two groups: group 1 with high velocity volume reduction (HvVR) and group 2 with lower velocity volume reduction or increase (LvVR).

Figure 5. OS in patients in the immunotherapy group, treated with pembrolizumab plus axitinib. Patients were further divided in two groups: group 1 with high velocity volume reduction (HvVR) and group 2 with lower velocity volume reduction or increase (LvVR).

Table 2. Association between survival outcomes and TGR at each CT assessment from first-line therapy’s start in patients treated with immune-based combination, single-agent TKI and in the overall population.

Outcome	Factor	TKI group (n = 18)			ICI/TKI group (n = 15)			All patients (n = 33)
		B	SE	p-value	B	SE	p-value	B	SE	p-value
PFS	TGR1	64.4	50.7	0.205	135.1	59.5	0.023	97.4	38.8	0.012
PFS	TGR2	179.7	95.5	0.060	296.3	257.2	0.249	154.5	69.2	0.025
PFS	TGR2-TGR1	−13.2	18.5	0.476	9.5	67.5	0.888	−10.7	16.2	0.509
OS	TGR1	124.8	64.0	0.051	158.4	79.6	0.046	156.4	51.7	0.002
OS	TGR2	106.5	74.5	0.153	139.6	258.2	0.589	102.1	69.4	0.141
OS	TGR2-TGR1	−27.3	35.6	0.444	15.6	123.0	0.899	−29.0	35.3	0.412

Abbreviations: TKI, tyrosine-kinase inhibitor; ICI, immune checkpoint inhibitor; TGR, tumor growth rate; PFS, progression-free survival; OS, overall survival; B, beta coefficient from the univariate Cox model; SE, standard error.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.