Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease: a randomized phase II study

7587 Background: Erlotinib is an oral epidermal growth factor receptor kinase inhibitor used in the treatment of advanced non-small-cell lung cancer (NSCLC). Resistance develops in patients (pts) who initially respond to erlotinib leading to progressive disease (PD). Sorafenib is an oral inhibitor of vascular endothelial and platelet-derived growth factor receptors and Raf kinases which play important roles in PD. This randomized phase II study evaluated the role of sorafenib and continued erlotinib or sorafenib alone in pts with progressive NSCLC following initial benefit with erlotinib. Methods: Eligible pts had IIIB/IV NSCLC, an ECOG PS 0-2, and had received ≤2 lines of therapy with the last being single-agent erlotinib. Pts must have PD following clinical benefit (complete/partial response/stable disease) from erlotinib for >8 weeks. Pts were randomized 1:1 to continue erlotinib at the dose administered at the time of PD with the addition of sorafenib 400 mg orally twice daily (Arm A) or to sorafenib alone (Arm B). Cycles were 28 days with restaging every 2 cycles. The primary endpoint was progression-free survival (PFS). Results: 52 pts were enrolled from 2/2008 to 3/2011 (A 24; B 28). Baseline characteristics were balanced between arms and included: median age 65 years (41-87); 65% female; 69% adenocarcinoma/large cell; and 96% PS <2. 41% of pts were either never smokers or smoked <100 cigarettes/lifetime. Pts received a median of 8 weeks of treatment per arm (0.6–67 weeks). The median PFS was 3.1 (95% CI 1.7-3.7) and 2.3 (1.7-3.6) months for A and B, respectively (p=.84). There were no grade 3/4 hematologic toxicities in either arm except grade 3 anemia in 1 pt (A). Severe nonhematologic toxicities in >5% included: fatigue 17%(A)/7%(B); diarrhea 17%/0; dehydration 13%/7%; hand-foot skin reaction 8%/8%, and anorexia 4%/7%. Conclusions: Sorafenib has modest activity when used in combination with erlotinib or as a single agent in pts with PD following benefit with erlotinib alone. Additional study to identify potential subsets of refractory pts who might derive the greatest benefit from sorafenib are warranted.

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A randomized phase II study of bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma: The Dutch BELOB study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2001 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2001-2001 ◽

Cited By ~ 32

Author(s):

Walter Taal ◽

Hendrika M Oosterkamp ◽

Annemiek M.E. Walenkamp ◽

Laurens Victor Beerepoot ◽

Monique Hanse ◽

...

Keyword(s):

Phase Ii ◽

Combination Treatment ◽

Phase Ii Study ◽

Controlled Trial ◽

Performance Status ◽

Single Agent ◽

Recurrent Glioblastoma ◽

Controlled Study ◽

Hematological Toxicity ◽

Randomized Phase Ii

2001 Background: Bevacizumab (BEV) is widely used in recurrent glioblastoma, alone or in combination with other agents. There is however no well-controlled trial to support the use for this indication. Methods: In a three-arm Dutch multicenter randomized phase II study (NTR 1929) patients were assigned to either BEV 10 mg/kg iv every 2 weeks, BEV 10 mg/kg iv every 2 weeks and 110 mg/m2 lomustine every 6 weeks, or lomustine 110 mg/m2every 6 weeks. Eligible were patients with histologically proven glioblastoma, with a first recurrence after chemo-irradiation with temozolomide, having concluded radiotherapy more than 3 months ago, with adequate bone marrow, renal and hepatic function, and WHO performance status (PS) 0-2. Primary endpoint was 9 months overall survival (OS); P0 was set at 35% and P1 at 55%. Progression was defined using RANO criteria. A safety review after the first 10 patients in the combination arm was preplanned. Results: Between December 2009 and November 2011, 153 patients were enrolled of whom 148 were considered eligible. Median age was 57 years (range, 24-77) and median WHO PS was 1. With respect to prognostic factors groups were well balanced. After review of the safety cohort the dosage lomustine in the combination arm was lowered to 90 mg/m2 because of hematological toxicity (predominantly thrombocytopenia without symptoms). At this lower lomustine dose level the combination treatment was in general well tolerated. Outcome: see Table. Conclusions: In this first well-controlled study on BEV in recurrent glioblastoma with a primary OS endpoint, combination treatment with bevacizumab and lomustine met the prespecified criterion for further investigation in clinical trials, whereas both drugs given as single agent failed to meet this criterion. Clinical trial information: NTR1929. [Table: see text]

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