Real-world experience of everolimus as second-line treatment in metastatic renal cell cancer after failure of pazopanib

Figures & data

Table 1 Patient and disease characteristics in the overall study population, N=31

Characteristics
Median age (range), years	58 (41–81)
Sex, n (%)
Male	19 (61)
Female	12 (39)
Histology, n (%)
Clear cell	29 (94)
Mixed histology	2 (6)
Performance status, n (%)
0	8 (26)
1	16 (51)
2	4 (13)
Missing	3 (10)
Previous nephrectomy, n (%)	19 (61)
Disease sites, n (%)
Renal bed	7 (23)
Bones	8 (26)
Liver	10 (32)
Lungs	22 (71)
Lymph nodes	14 (45)
Brain	2 (7)
Other	11 (36)
Previous treatment with pazopanib
MSKCC risk score, n (%)
Favorable	4 (13)
Intermediate	12 (39)
Poor	8 (26)
Missing	7 (22)
Duration of pazopanib therapy, months
Median (range)	5.6 (0.5–19)
>3	22 (70%)
>6	11 (35%)
>9	6 (19%)

Abbreviation: MSKCC, Memorial Sloan-Kettering Cancer Center.

Figure 1 Kaplan–Meier curves of PFS and OS from the initiation of everolimus in 31 patients with metastatic renal cell carcinoma treated with the sequence pazopanib–everolimus.

Abbreviations: OS, overall survival; PFS, progression-free survival.

Figure 2 Kaplan–Meier curves of overall survival from the initiation of everolimus in 31 patients with metastatic renal cell carcinoma treated with the sequence pazopanib–everolimus according to the time of exposure to first-line pazopanib: ≤9 months and >9 months.

Table 2 Median PFS and OS after everolimus initiation according to exposure to pazopanib

Time on pazopanib, months	n	PFS, months			OS, months
		Median	95% CI	p-value	Median	95% CI	p-value
<3	9	2.3	0.9–7	0.3704	6.4	1.8–8.7	0.0021
≥3	22	3.5	2.6–5.5		11.1	7.5–16.4
<6	20	3.2	1.9–5	0.5884	7.5	4.4–11.4	0.0160
≥6	11	3.5	1–9.9		15.9	6.5–NR
<9	25	2.8	2.1–4.4	0.0970	7.9	5.7–11.1	0.0066
≥9	6	6.4	3–NR		NR	8.9–NR

Abbreviations: NR, not reached; OS, overall survival; PFS, progression-free survival.

Table 3 Adverse events on everolimus treatment

Adverse event	Grade, n (%)				N (%)
	1	2	3	4	Total
Anemia	2 (7)	4 (13)	2 (7)	1 (3)	9 (29)
Stomatitis	4 (13)	1 (3)	3 (10)	0	8 (26)
Pneumonitis	2 (7)	2 (7)	2 (7)	0	6 (19)
Fatigue	1 (3)	2 (7)	0	0	3 (10)
Bone/joint pain/toothache	2 (7)	0	1 (3)	0	3 (10)
Bleeding	0	1 (3)	1 (3)	0	2 (7)
Lack of appetite	1 (3)	1 (3)	0	0	2 (7)
Diarrhea	2 (7)	0	0	0	2 (7)
Fever	2 (7)	0	0	0	2 (7)
Rash	1 (3)	1 (3)	0	0	2 (7)
Hypercalcemia	0	1 (3)	0	1 (3)	2 (7)
Liver function test elevation	1 (3)	1 (3)	0	0	2 (7)
Alopecia	1 (3)	0	0	0	1 (3)
Pleural effusion	0	0	1 (3)	0	1 (3)
Pulmonary embolism	0	0	1 (3)	0	1 (3)
Acute renal failure–proteinuria	0	0	1 (3)	0	1 (3)
Hyperlipidemia	1 (3)	0	0	0	1 (3)
Edema	0	1 (3)	0	0	1 (3)

Table 4 Efficacy of everolimus as second-line treatment in mRCC patients

Study (reference)	Design	Number of patients receiving second-line everolimus (% of everolimus-treated population)	Prior therapy	PFS	OS
RECORD-1^Citation8	Phase III	43 (16)	Sunitinib	4.6	NR
		18 (6)	Sorafenib	3.8	NR
RECORD-4^Citation9	Phase II	58 (100)	Sunitinib	5.7	NR
Albiges et al^Citation10	Pooled analysis, noninterventional	493 (78)	Sunitinib, sorafenib, and bevacizumab	5.8	11.2
CHANGE^Citation7	Prospective, noninterventional	211 (72)	Sunitinib, sorafenib, pazopanib (4%), bevacizumab, and cytokines	6.9*	NR
METEOR^Citation19	Phase III	136 (72)	Sunitinib, sorafenib, pazopanib (41%), bevacizumab, cytokines, and nivolumab	3.8*,#	NR
CheckMate 025^Citation20	Phase III	297 (72)	Sunitinib, pazopanib (32%), and axitinib	4.4*,#	19.6*
Motzer et al^Citation21	Phase II	50 (100)	Sunitinib, sorafenib, pazopanib (25%), axitinib, and bevacizumab	5.5*	NR
Vogelzang et al^Citation22	Retrospective	22 (100)	Pazopanib (100%)	5.7**	16.0**
Bellmunt et al^Citation23	Retrospective	13 (100)&	Pazopanib (100%)	2.4	20.8
RESCUE	Retrospective	31 (100)	Pazopanib (100%)	3.5	8.9

Notes: Median PFS and OS are provided in months.

* PFS not reported for the pazopanib subgroup;

# pure second-line everolimus analysis not reported;

** PFS for both temsirolimus and everolimus treated patients.

& 2 patients had received cytokines prior to pazopanib.

Abbreviations: mRCC, metastatic renal cell carcinoma; NR, not recorded; OS, overall survival; PFS, progression-free survival.

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