Entry Detail
| General information | |
| Database: | DB00480 |
| Objective: | This internationalphase III trial (Investigating Torisel As SecondLine Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as secondline therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib. |
| Authors: | Hutson TE, et al |
| Title: | Randomizedphase III trial of temsirolimus versus sorafenib as secondline therapy after sunitinib in patients with metastatic renal cell carcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2014 |
| PMID: | 24297950 |
| Trial Design | |
| Clinical Trial Id: | NCT00474766 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | international, randomized, openlabel, multicenter, phase IIItrial |
| Key Patients Feature: | Eligible patients, age more than 18 years, had histologically confirmedmRCC (any histology) with documentation of radiologic progressive disease(PD) according to Response Evaluation Criteria for Solid Tumors (RECIST, version 1.0)16 or clinical PD, as judged by investigator, while receiving firstlinesunitinib. Patients must have received at least one 4week cycle of continuoussunitinib, regardless of dose; discontinuation because of intolerance alone wasunacceptable for inclusion. Patients must have completed sunitinib, palliativeradiation therapy, or surgery 2 weeks before randomization.Key eligibility criteria were at least one measurable (nonbone) targetlesion per RECIST; Eastern Cooperative Oncology Group performance status0 or 1; life expectancy 12 weeks; and adequate hematologic, hepatic, renal, and cardiac function. Patients were excluded if they had brain metastases, unstable coronary artery disease or myocardial infarction during preceding 6months, hypertension uncontrolled by medication, active ketonuria secondary to poorly controlled diabetes mellitus, history of pulmonary hypertension or interstitial lung disease, or prior systemic therapy other than sunitinib formRCC. All patients provided written informed consent. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | intravenous temsirolimus 25 mg once weekly (n = 259) |
| Treatment Info: | patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (less than and equal to or > 180 days), prognostic risk, histology (clear cell or nonclear cell), and nephrectomy status. |
| Primary End Point: | progression free survival (PFS) by independent review committee assessment. |
| Secondary End Point: | Safety, objective response rate (ORR), and overall survival (OS) |
| Patients Number: | 512 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | In Temsirolimus 25 mg IV Once per week (n = 259), complete response 0, partial response 8%; Sorafenib 400 mg Orally Twice per Day (n = 253), complete response <1%, partial response 8%, |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively (stratified hazard ratio [HR], 0.87; 95% CI, 0.71 to 1.07; twosidedP=0.19). |
| Median OS A vs. C: | Median OS in the temsirolimus and sorafenib arms was 12.3 (95% CI, 10.1 to14.8 months) and 16.6 months (95% CI, 13.6 to 18.7 months), respectively. |
| Adverse Event(agent arm): | In both arms, the same proportion of patients (99.6%) had one or more AE (allgrade; allcause). The most common AEs with temsirolimus were rash, fatigue, cough, anemia, and nausea versus diarrhea, palmarplantar erythrodysesthesia (PPE), decreased appetite, rash, and fatigue with sorafenib. Common AEs (all grade) occurring with more than 10% increased incidence with temsirolimus compared with sorafenib were cough, anemia, mucosal inflammation, dyspnea, peripheral edema, stomatitis, hypertriglyceridemia, hypercholesterolemia, epistaxis, and hyperglycemia. With sorafenib, AEs that occurred more than 10% more frequently compared with temsirolimus were diarrhea, PPE, alopecia, hypertension, and dysphonia. |
| Conclusions: | In patients with mRCC and progression on sunitinib, secondline temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC. |