Treatment patterns in metastatic renal cell carcinoma: a retrospective review of medical records from US community oncology practices

Figures & data

Table 1. Patient characteristics at the initiation of second targeted therapy.

Characteristics	N = 433
Age at initial diagnosis of mRCC (yrs), mean (SD)	63.1 (10.6)
Female, n (%)	155 (35.8)
Duration of mRCC prior to second targeted therapy, mean (SD)	12.6 (12.6)
Treatments prior to the first targeted therapy, n (%)
No treatment	163 (37.6)
Systemic therapy (other than targeted therapy)^a	33 (7.6)
Surgery^b	240 (55.4)
Radiation therapy	33 (7.6)
Responded while on the first targeted therapy^c, n (%)	271 (66.6)
Progressed while on the first targeted therapy^c, n (%)	368 (87.8)
Site of metastasis at the initiation of second targeted therapy, n (%)
Lung	353 (81.5)
Lymph nodes	241 (55.7)
Bone	236 (54.5)
Liver	129 (29.8)
Soft tissue other than lymph nodes	85 (19.6)
Adrenal glands	64 (14.8)
Central nervous system	25 (5.8)
Other metastatic sites^d	8 (1.8)
Clear cell RCC, n (%)	344 (79.4)
ECOG performance status at the initiation of second targeted therapy, n (%)
0	59 (14.1)
1	230 (55.0)
2–4	129 (29.8)
KPS at the initiation of second targeted therapy, n (%)
70%, 100%	248 (87.9)
0%, 60%	34 (12.1)
MSKCC at the initiation of second targeted therapy, n (%)
Favorable	78 (22.4)
Intermediate	182 (52.3)
Poor	88 (25.3)
Comorbidities at the initiation of second targeted therapy^e, n (%)
Hypertension	276 (64.0)
Hypercholesterolemia	189 (44.1)
Diabetes mellitus (type I or II)	137 (31.9)
Chronic renal disease	130 (30.2)
Cardiovascular diseases	90 (20.9)

^aSystemic therapy prior to initiation of the first targeted therapy included interferon, interleukin-2 and chemotherapy.

^bSurgery included complete and partial nephrectomy and lung metastasis resection.

^cReported responses or progressions were based on radiographic evidence, physical exams, or improved or worsening cancer-related symptoms.

^dOther metastatic sites included pancreas (3), brain (1), renal fossa (1), scalp (1), bladder (1), peritoneal surface (1), spleen (1), and omental metastatic disease (1).

^eOnly the five most prevalent comorbidities are presented in the table.

ECOG, Eastern Cooperative Oncology Group performance status; KPS, Karnofsky performance status; MSKCC, Memorial Sloan-Kettering Cancer Center prognostic score; mRCC, metastatic renal cell carcinoma; N, number; SD, standard deviation; yrs, years.

Figure 1. Observed treatment sequences. mTOR, mammalian target of rapamycin inhibitor; N, number; VEGF, vascular endothelial growth factor. 1. In this analysis, bevacizumab is grouped with the TKI class because it has the same therapeutic target as the TKI agents. 2. Out of a total of 433 patients in this study, only 91 initiated third targeted therapy. No patients treated with mTORs during first-line and second-line treatment received third-line therapy.

Table 2. Description of treatment patterns of second targeted therapy.

Characteristics	Overall (n = 433)	Second Targeted Therapy
		Everolimus (Afinitor) (n = 154)	Bevacizumab (Avastin) (n = 33)	Sorafenib (Nexavar) (n = 36)	Sunitinib (Sutent) n = 62)	Temsirolimus (Torisel) (n = 73)	Pazopanib (Votrient) (n = 65)
Length of follow up (KM estimates), median (95% CI)	4.9 (4.7–5.2)	4.9 (4.4–5.9)	4.2 (2.3–6.1)	9.1 (4.9–12.3)	5.8 (4.7–8.1)	4.9 (3.7–5.8)	4.9 (4.0–7.2)
Duration of second targeted therapy (KM estimates), median (95% CI)	8.6 (6.9–10.4)	10.8 (5.9–11.5)	4.4 (2.3–NR)	6.4 (4.4–10.3)	10.3 (8.0–13.1)	7.7 (6.1–10.7)	9.1 (6.3–14.7)
Discontinued second targeted therapy, n (%)	191 (44.1)	58 (37.7)	17 (51.5)	22 (61.1)	30 (48.4)	36 (49.3)	27 (41.5)
Among those who discontinued, reason for discontinuation, n (%)
Disease progression	140 (73.3)	41 (70.7)	14 (82.4)	16 (72.7)	21 (70.0)	26 (72.2)	21 (77.8)
Drug toxicity/drug intolerance	18 (9.4)	3 (5.2)	2 (11.8)	4 (18.2)	4 (13.3)	2 (5.6)	3 (11.1)
Death	17 (8.9)	6 (10.3)	0 (0.0)	1 (4.5)	3 (10.0)	5 (13.9)	2 (7.4)
Other medical reasons^a	7 (3.7)	5 (8.6)	0 (0.0)	0 (0.0)	1 (3.3)	1 (2.8)	0 (0.0)
Non-medical reasons	6 (3.1)	3 (5.2)	1 (5.9)	0 (0.0)	0 (0.0)	1 (2.8)	1 (3.7)
Non-response without progression	3 (1.6)	0 (0.0)	0 (0.0)	1 (4.5)	1 (3.3)	1 (2.8)	0 (0.0)
Among those who discontinued, status after discontinuation, n (%)
Received third targeted therapy	96 (50.3)	25 (43.1)	5 (29.4)	14 (63.6)	18 (60.0)	18 (50.0)	16 (59.3)
Deceased	59 (30.9)	22 (37.9)	8 (47.1)	5 (22.7)	7 (23.3)	10 (27.8)	7 (25.9)
Received best supportive care	31 (16.2)	8 (13.8)	4 (23.5)	3 (13.6)	4 (13.3)	7 (19.4)	4 (14.8)
Other^b	5 (2.6)	3 (5.2)	0 (0.0)	0 (0.0)	1 (3.3)	1 (2.8)	0 (0.0)
Dose adjustment during second targeted therapy, n (%)
No adjustment	316 (73.0)	120 (77.9)	24 (72.7)	26 (72.2)	29 (46.8)	56 (76.7)	52 (80.0)
Decreased total monthly dose	70 (16.2)	15 (9.7)	4 (12.1)	7 (19.4)	27 (43.5)	6 (8.2)	11 (16.9)
Increased total monthly dose	3 (0.7)	1 (0.6)	0 (0.0)	0 (0.0)	1 (1.6)	1 (1.4)	0 (0.0)
Dose interruptions (i.e. medically recommended interruption of therapy)	29 (6.7)	13 (8.4)	2 (6.1)	3 (8.3)	5 (8.1)	4 (5.5)	2 (3.1)
Drug holidays (i.e. elective time off therapy)	22 (5.1)	3 (1.9)	1 (3.0)	4 (11.1)	4 (6.5)	6 (8.2)	3 (4.6)
Maintained total monthly dose but altered frequency	3 (0.7)	1 (0.6)	0 (0.0)	0 (0.0)	0 (0.0)	1 (1.4)	1 (1.5)
Other^c	9 (2.1)	3 (1.9)	5 (15.2)	0 (0.0)	1 (1.6)	0 (0.0)	0 (0.0)
Reason for dose adjustment during second targeted therapy (among those with adjustment), n (%)
Drug toxicity/drug intolerance	82 (70.1)	24 (70.6)	4 (44.4)	9 (90.0)	24 (72.7)	11 (64.7)	10 (76.9)
Disease progression	20 (17.1)	3 (8.8)	0 (0.0)	3 (30.0)	9 (27.3)	3 (17.6)	1 (7.7)
Non-medical reasons	7 (6.0)	2 (5.9)	0 (0.0)	0 (0.0)	1 (3.0)	1 (5.9)	3 (23.1)
Other medical reasons^d	7 (6.0)	4 (11.8)	0 (0.0)	0 (0.0)	1 (3.0)	2 (11.8)	0 (0.0)
Non-response without progression	3 (2.6)	1 (2.9)	0 (0.0)	1 (10.0)	0 (0.0)	0 (0.0)	1 (7.7)

^aOther medical reasons for discontinuation included lung metastasis resected (1), myocardial infarction (1), liver failure (1), congestive heart failure (1), severe anemia (1), general non-compliance (1), and lost to follow up (1).

^bOther statuses included: continuing follow-up and monitoring for metastatic disease (1), hospice care (1), discussed trying everolimus, but patient reluctant to try anything new due to toxicities (1), waiting for drug assistance to start axitinib (1), and patient transferred and no further follow-up (1).

^cOther dose adjustments included discontinued interferon (5), added gemzar (1), discontinued the treatment (1), too early (1), and changed insurance (1).

^dOther medical reasons for dose adjustment included fatigue (2), admitted to hospital (1), patient wanted break (1), worsening shortness of breath (1), adjust dose because of kidney transplant (1), and liver failure (1).

CI, confidence interval; KM, Kaplan–Meier; N, number.

Table 3. Treatment outcomes for mRCC patients sorted by different first- and second-line treatment sequences.

Sequence	N	Death (%)	Median OS (months)	Progressed or died (%)	Median PFS (months)	Treatment failure (%)	Median TTF (months)	Median follow-up (months)
VEGF–mTOR	221	19.9	Not reached*	40.3	10.8	45.7	8.9	4.9
VEGF–VEGF	113	21.2	27.4	45.1	10.3	55.8	7.9	6.1
mTOR–VEGF	93	21.5	23.6	39.8	10.3	43.0	10.3	4.9
mTOR–mTOR	6	16.7	Not reached†	16.7	Not reached‡	50.0	Not reached**	4.0

^aIn this analysis, bevacizumab is grouped with the TKI therapy as VEGF-targeted agents.

^bPFS is defined as time from second targeted therapy initiation to the earlier date of physician-assessed disease progression or death; patients were censored at the earlier of the last follow-up visit or second-line treatment discontinuation.

^cTTF is defined as time from second targeted therapy initiation to the earliest date of physician-assessed disease progression, treatment discontinuation, or death; patients were censored at the last follow-up visit.

^dSurvival time for patients with data entry errors were imputed using the medians of the rest of the patient population. Separate medians were derived for those with or without the event of interest.

*The last patient with VEGF–mTOR treatment sequence was censored at 28.5 months; 51.8% patients remained alive at the last censoring date.

†The last patient with mTOR–mTOR treatment sequence was censored at 4.5 months; 75% patients remained alive at the last censoring date.

‡The last patient with mTOR–mTOR treatment sequence was censored at 4.5 months; 80% patients had progression-free survival at the last censoring date.

**The last patient with mTOR–mTOR treatment sequence was censored at 4.5 months; 50% patients remained on treatment without progression at the last censoring date.

mTOR, mammalian target of rapamycin inhibitor; mRCC, metastatic renal cell carcinoma; N, number; OS, overall survival; PFS, progression-free survival; TTF, time to treatment failure; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor.