TORISEL Clinical Trial Design and Results¹

TORISEL was studied in a phase 3, multicenter, 3-arm, randomized, open-label study conducted in 626 previously untreated patients with advanced renal cell carcinoma (RCC) with at least 3 of 6 prognostic risk factors.

This study was called the Global Advanced Renal Cell Carcinoma (ARCC) Study. Objectives were to compare the following parameters in patients receiving interferon-alpha (IFN-α) vs. patients receiving TORISEL or TORISEL plus IFN-α:

• Primary end point: overall survival (OS)
• Secondary end points included progression-free survival (PFS) and objective response rate (ORR)
• Safety profile

Trial Design

Patient randomization (N=626)^1-3

Treatment with the combination of TORISEL 15 mg and IFN-α was associated with an increased incidence of multiple adverse reactions and did not result in a significant increase in overall survival (OS) when compared with IFN-α alone.^1-3

For this reason, the following results do not include those associated with the combination arm in the Global ARCC Study.

Disease Characteristics^2,3

Characteristic	TORISEL 25 mg (%) n=209	IFN-α up to 18 MU 3x weekly (%) n=207
Primary cell type     Clear     Other	81 19	82 18
Prior nephrectomy     No     Yes	34 66	33 67

Patient age, gender, and race were comparable across all three treatment arms.¹

Trial results

• TORISEL demonstrated a statistically significant 49% increase in median overall survival (OS) compared with interferon-alpha (IFN-α) (P=0.0078^*)¹
• The O’Brien-Fleming boundary for early success (P<0.0159) was reached at the second planned interim analysis^1,2

Primary End Point: Median Overall Survival¹

Primary end point	TORISEL (n=209)	IFN-α (n=207)	P-value†	Hazard Ratio (95% CI)‡
Median OS§ Months (95% CI)	10.9 (8.6, 12.7)	7.3 (6.1, 8.8)	0.0078*	0.73 (0.58, 0.92)

Secondary End Points^1-3*

Parameter	TORISEL 25 mg (n=209)	IFN-α (n=207)	% Difference	P-value†	Hazard Ratio (95% CI)‡
Median PFS§ by independent review Months (95% CI)	5.5 (3.9-7.0)	3.1 (2.2-3.8)	77%	0.0001	0.66 (0.53-0.81)
Median PFS§ by investigator review Months (95% CI)	3.8 (3.6-5.2)	1.9 (1.9-2.2)	100%	0.0005	0.69 (0.57-0.85)
Median TTF|| Months (95% CI)	3.8 (3.5, 3.9)	1.9 (1.7- 1.9)	100%	<0.0001	0.61 (0.50-0.74)
ORR¶ % (95% CI)	8.6% (4.8-12.4)	4.8% (1.9-7.8)	79%	0.1232#	NA
Clinical benefit rate (CR, PR, or SD for ≥24 weeks) % (95% CI)**	32.1% (25.7-38.4)	15.5% (10.5-20.4)	107%	<0.0001	NA

Clinical trials

• Get a reprint of the TORISEL vs. IFN-α trial from the New England Journal of Medicine.
• Find listings for ongoing TORISEL clinical trials
• Participate in an interactive review of the published TORISEL phase 3 clinical trial.

Important Safety Information

Important Safety Information

• Hypersensitivity reactions manifested by symptoms, including, but not limited to anaphylaxis, dyspnea, flushing, and chest pain have been observed with TORISEL.
• Serum glucose, serum cholesterol, and triglycerides should be tested before and during treatment with TORISEL.
  • The use of TORISEL is likely to result in hyperglycemia and hyperlipemia. This may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycemic agent therapy and/or lipid-lowering agents, respectively.
• The use of TORISEL may result in immunosuppression. Patients should be carefully observed for the occurrence of infections, including opportunistic infections.
• Cases of interstitial lung disease, some resulting in death, have occurred. Some patients were asymptomatic and others presented with symptoms. Some patients required discontinuation of TORISEL and/or treatment with corticosteroids and/or antibiotics.
• Cases of fatal bowel perforation occurred with TORISEL. These patients presented with fever, abdominal pain, metabolic acidosis, bloody stools, diarrhea, and/or acute abdomen.
• Cases of rapidly progressive and sometimes fatal acute renal failure not clearly related to disease progression occurred in patients who received TORISEL.
• Due to abnormal wound healing, use TORISEL with caution in the perioperative period.
• Patients with central nervous system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving TORISEL.
• Live vaccinations and close contact with those who received live vaccines should be avoided.
• Patients and their partners should be advised to avoid pregnancy throughout treatment and for 3 months after TORISEL therapy has stopped.
• The most common (incidence ≥30%) adverse reactions observed with TORISEL are: rash (47%), asthenia (51%), mucositis (41%), nausea (37%), edema (35%), and anorexia (32%). The most common laboratory abnormalities (incidence ≥30%) are anemia (94%), hyperglycemia (89%), hyperlipemia (87%), hypertriglyceridemia (83%), elevated alkaline phosphatase (68%), elevated serum creatinine (57%), lymphopenia (53%), hypophosphatemia (49%), thrombocytopenia (40%), elevated AST (38%), and leukopenia (32%).
• Most common grades 3/4 adverse events and laboratory abnormalities included asthenia (11%), dyspnea (9%), hemoglobin decreased (20%), lymphocytes decreased (16%), glucose increased (16%), phosphorus decreased (18%), and triglycerides increased (44%).
• Strong inducers of CYP3A4/5 (eg, dexamethasone, rifampin) and strong inhibitors of CYP3A4 (eg, ketoconazole, atazanavir) may decrease and increase concentrations of the major metabolite of TORISEL, respectively. If alternatives cannot be used, dose modifications of TORISEL are recommended.
• St. John’s Wort may decrease TORISEL plasma concentrations, and grapefruit juice may increase plasma concentrations of the major metabolite of TORISEL, and therefore both should be avoided.
• The combination of TORISEL and sunitinib resulted in dose-limiting toxicity (Grade 3/4 erythematous maculopapular rash, and gout/cellulitis requiring hospitalization).

Please see the full Prescribing Information for TORISEL.

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