A single-arm, open-label, multicenter phase II trial (CheckMate 172) of nivolumab (NIVO) safety in European patients (pts) with advanced melanoma (MEL) who have progressed after ipilimumab therapy (IPI).

7001 Background: Sunitinib malate (SU11248) is an oral, multitargeted tyrosine kinase inhibitor targeting VEGFR, PDGFR, KIT, FLT3 and RET on tumor cells, tumor neovasculature and pericytes. This is the initial report of an open-label, two-stage, multicenter phase II trial evaluating the single-agent activity of sunitinib in refractory NSCLC. Methods: Eligibility criteria included confirmed diagnosis of NSCLC, ECOG PS 0–1, no recent gross hemoptysis, no brain metastases, patients (pts) previously treated with 1–2 chemotherapy regimens, and adequate end-organ function. Pts received sunitinib at 50 mg/day po for 4 weeks (wks) followed by 2 wks off treatment (6 wks considered a cycle). Results: A total of 64 pts were enrolled and 63 pts treated, median age 61 yrs (range 33–87); adenocarcinoma (64%), squamous cell carcinoma (22%), other (14%); 66% male; PS 0:1, 45%:55%; median number of prior regimens: 2 (range 1–4); median time since the prior regimen: 2 months (range 1–21). To date, 63 pts have started cycle 1, 46 cycle 2, 22 cycle 3, 6 cycle 4 and 1 cycle 5. Grade 3–4 toxicities included fatigue/asthenia (21%), nausea (7%), vomiting (7%), abdominal pain (7%), and hypertension (5%). Most toxicities were grade 1–2 and included asthenia/fatigue (68%), anorexia (40%), dyspnea (37%), cough (35%), nausea (33%), mucositis (32%), dysgeusia (25%), diarrhea (21%), vomiting (19%), and constipation (19%). Grade 5 toxicities include pulmonary hemorrhage (n=2) and cerebral hemorrhage (n=1). Thus far, 6 confirmed partial responses have been observed among 63 treated pts (9.5%, 95% CI: 3.6–19.6%). Stable disease has been observed in an additional 12 pts (19.0%). Survival data are pending and will be presented. Conclusions: Sunitinib has provocative single-agent activity in previously treated pts with recurrent and advanced NSCLC, with the level of activity similar to currently approved agents. Sunitinib is well tolerated in this population. The trial is being extended to explore a continuous dosing strategy of sunitinib at 37.5 mg/day po. Based on these results, further trials are warranted and are ongoing with sunitinib in combination with standard agents/regimens. [Table: see text]

Download Full-text

Multicenter Phase II Trial of Temozolomide in Patients With Anaplastic Astrocytoma or Anaplastic Oligoastrocytoma at First Relapse

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.9.2762 ◽

1999 ◽

Vol 17 (9) ◽

pp. 2762-2762 ◽

Cited By ~ 529

Author(s):

W.K. Alfred Yung ◽

Michael D. Prados ◽

Ricardo Yaya-Tur ◽

Steven S. Rosenfeld ◽

Michael Brada ◽

...

Keyword(s):

Phase Ii ◽

Safety Profile ◽

Anaplastic Astrocytoma ◽

Phase Ii Trial ◽

Single Agent ◽

Objective Response ◽

Survival Rates ◽

Open Label ◽

Multicenter Phase ◽

First Relapse

PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m2/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m2/d; the dose could be increased to 200 mg/m2/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.

Download Full-text