Xiaoyu Jia

Phase II trial of sunitinib in patients with metastatic non-clear cell renal cell carcinoma

SummarySunitinib is associated with a robust objective response rate in patients with metastatic clear cell renal cell carcinoma (RCC). The primary objective of this phase II clinical trial was to assess the overall response rate for sunitinib in patients with papillary metastatic RCC as well as other non-clear cell histologies. A Simon 2-stage design was used to determine the number of papillary metastatic RCC patients for enrollment, and allowed for descriptive response data for other non-clear cell histologies. Twenty-three patients were enrolled, including 8 with papillary renal cell carcinoma (RCC) and the remainder with other non-clear cell histologies (unclassified in 5 patients). All patients received 50xa0mg of oral sunitinib in cycles of 4xa0weeks followed by 2xa0weeks of rest (4/2). The trial was stopped early because of slow accrual; no responses were observed in the 8 patients with papillary RCC. In the 22 evaluable patients, best response to sunitinib included a partial response in 1 patient with unclassified RCC, stable disease in 15, and progression in 6. The median progression-free survival was 5.5xa0months (95% CI, 2.5–7.1) in all 23 patients, and 5.6xa0months for the 8 papillary patients (95% CI, 1.4–7.1). The robust objective responses sunitinib had produced in clear cell RCC could not be demonstrated in this study comprised of patients with non-clear cell histologies.

Long-Term Response to Sunitinib Therapy for Metastatic Renal Cell Carcinoma

BACKGROUNDnSunitinib achieves objective response and prolongs progression-free survival (PFS) in patients with metastatic renal cell carcinoma (RCC). A subset of patients achieves long-term responses. The characteristics of patients who achieved long-term response (defined as patients achieving ongoing complete response [CR] or remaining progression free for > 18 months while receiving sunitinib) are reported.nnnPATIENTS AND METHODSnA database of 186 patients treated with sunitinib alone (n = 89) or in combination (n = 97) in 9 clinical trials was reviewed; all had 1 year or more follow-up from sunitinib start to data cutoff for analysis. Median PFS was 10.8 months (95% CI, 8.3-13.3); median overall survival (OS) was 30.4 months (95% CI, 21.5-36.8 months) for the 186 patients. Thirty-four patients were identified as long-term responders because they either had durable CR or remained progression free while receiving sunitinib for > 18 months.nnnRESULTSnBest response for 34 long-term responders was CR in 3 patients, partial response (PR) in 24 patients, and stable disease in 7 patients. The median duration of sunitinib therapy was 24.9 months (range, 18.1-73.9 months). The median PFS among the long-term responders was 17.4 months (95% CI, 7-29.9 months) at a landmark PFS analysis performed after 18 months from treatment start. Univariate analysis from the 186 patients identified bone metastasis, lung metastasis, and intermediate/poor risk groups as adverse prognostic factors for long-term response.nnnCONCLUSIONnSunitinib achieves long-term response in a subset of patients with metastatic RCC. Lack of bone metastasis or lung metastasis and good MSKCC risk status may predict long-term response.

Thyroid Transcription Factor–1 Expression Is an Independent Predictor of Recurrence and Correlates with the IASLC/ATS/ERS Histologic Classification in Patients with Stage I Lung Adenocarcinoma

In the current study, the authors investigated whether thyroid transcription factor‐1 (TTF‐1) expression is correlated with the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and whether it stratifies patients with stage I lung adenocarcinoma with respect to disease recurrence.

Safety and Efficacy of Targeted Therapy for Renal Cell Carcinoma With Brain Metastasis

BACKGROUNDnBrain metastases are associated with a poor prognosis in patients with renal cell carcinoma (RCC). The role of targeted therapy in this setting is not well established. The primary objective was to assess overall survival (OS) and neurologic events in patients with brain metastasis treated with targeted agents.nnnPATIENTS AND METHODSnPatients with RCC treated with targeted agents for brain metastasis between 2002 and 2012 were retrospectively identified. Kaplan-Meier methodology and a Cox proportional hazards model were used to analyze the association between clinical features and OS.nnnRESULTSnOf 65 patients identified, 52 (80%) were treated with antiangiogenic agents and 13 (20%) received inhibitors of mTOR (mechanistic target of rapamycin [serine/threonine kinase]); 57 (88%) had local therapy for brain metastasis, including surgery in 3 (5%), radiation therapy in 36 (55%), and both surgery and radiotherapy in 18 (28%). Median follow-up was 12.3 months (1.1-58.8). Median treatment duration for targeted therapy as first-line therapy was 3.4 months (0.3-31.9). The median OS was 12.2 months (95% CI, 8.0-15.5). The risk group according to the Memorial Sloan Kettering Cancer Center (MSKCC) stratification (P = .001), the histology subtype (clear vs. other) (P < .0001), and the number of brain lesions (1 vs. ≥ 2) (P = .004) correlated with OS on multivariate analysis. Neurologic complications were identified in 5 patients (8%), including 2 with radiation necrosis and 3 with brain metastasis hemorrhage.nnnCONCLUSIONnThe use of targeted agents in the multimodal treatment of patients with RCC and brain metastasis was not associated with excessive neurologic adverse events. Clear cell histology, favorable MSKCC risk status, and solitary brain metastasis are associated with more favorable OS.

Clinical features, presentation, and tolerance of platinum-based chemotherapy in germ cell tumor patients 50 years of age and older

Germ cell tumors (GCTs) primarily affect adolescent and young adult men. Detailed clinical and treatment characteristics in older men are lacking.

Long-term responders to sunitinib therapy for metastatic renal cell carcinoma (mRCC).

4610 Background: Sunitinib has established efficacy in mRCC pts (NEJM 2007; 356:115). We report long-term responders, defined as patients (pts) achieving ongoing complete response (CR) or remaining progression-free for ≥ 18 months on sunitinib. Methods: From 1/03-3/06, 139 pts were treated with sunitinib alone (64 pts) or in combination (75 pts) on 7 clinical trials at MSKCC. Median progression-free survival (PFS) was 11 mos (95% CI 8-15); median OS was 24 mos (95% CI 18-34). 24 of the 139 were identified as long-term responders. Results: Characteristics for the 24 and the entire cohort of 139 were examined (Table). Best response was CR in 3, partial response in 19, and stable disease in 2 pts. Median duration of sunitinib therapy was 26 months (range 18-59) 4 remain on therapy, 15 discontinued for progression, 3 discontinued for toxicity, 1 remains off therapy after CR and 1 discontinued following resection of metastasis. Landmark PFS analysis was performed at 18 months: median PFS was 25 months (95% CI,...

Safety and efficacy of targeted therapy for renal cell carcinoma (RCC) with brain metastasis.

497 Background: Brain metastases (Bm) in RCC are associated with poor prognosis. The safety and efficacy of TT in this setting is not well established since patients (pts) with Bm were excluded from pivotal clinical trials. The primary objective was to assess safety and efficacy of TT in pts with Bm. Methods: Pts with mRCC treated with ≥ 28 days of TT after Bm diagnoses were retrospectively identified. Kaplan-Meier method and Cox proportional hazards model were used to analyze the association between clinical features and OS. Results: 65 pts were identified, including 52 (80%) treated with anti-angiogenic agents and 13 (20%) treated with mTOR inhibitors. Most pts had extracranial metastasis (98%) and 54% had ≥ 2 brain lesions. Fifty seven pts (88%) had local therapy for Bm before TT including surgery in 3 (5%), radiation therapy (RT) in 36 (55%) and both surgery and RT in 18 (28%). Median follow-up was 12.3 months (1.1 – 58.8). Median treatment duration was 3.4 months (0.3 – 31.9) for 1st line and 1.9 mon...