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Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors.

Publication ,  Journal Article
Howard, LA; Bullock, KE; Bendell, JC; Uronis, HE; Vlahovic, G; Blobe, GC; Riedel, RF; Nixon, AB; Gockerman, JP; Hurwitz, HI
Published in: J Clin Oncol
May 20, 2009

3551 Background: In preclinical models, VEGF, mTOR, and EGFR inhibitors have anti-tumor and anti-angiogenesis effects as monotherapies and in combination. B inhibits VEGF; E inhibits mTOR; P inhibits EGFR. There is also potential for interaction between the pathways. Previously BE and BE + erlotinib were evaluated and showed signs of clinical activity. METHODS: Patients (pts) with refractory advanced solid tumors were accrued in a phase I dose escalation of B + E + P on a 28d cycle. Dose levels are shown in the table below. DLT was defined as any treatment-related grade 4 heme, grade 3/4 non-heme adverse event (AE), or receiving <85% any study drug in Cycle 1. Blood, skin, and tumor biopsies pre- and on-treatment were collected for correlative biomarkers of angiogenesis. RESULTS: At this time, 12 pts (3M: 9F) are evaluable for toxicity; 9 for efficacy. Median age: 54 years (range 23-72). 9 of 12 pts had prior B exposure. Dose level 1 was expanded due to 1/3 DLT, with total of 3/6 DLT (Grade (Gr) 3 mucositis (n=2), Gr3 hypokalemia (n=1)). Dose level -1 had 3/3 DLT (Gr3, Gr4 mucositis (n=2), Gr3 non-acneform rash (n=1)). Dose level -2 had 0/3 pts DLT. Gr 3-4 related toxicities in cycle 2+: hypokalemia (n=4); hypophosphatemia (n = 1); hypomagnesemia (n = 1); diarrhea (n=1); hoarseness (n=1). Other events of interest were: Gr1-2 mucositis (n=7); Gr1 hyperlipidemia (n=5); Gr1-2 hyperglycemia (n=4); Gr2 hypertension (n=2); Gr1-2 neutropenia (n=5); Gr1-2 thrombocytopenia (n=5). 8/9 evaluable pts had SD as best response (median 26 wks, range 8+ to 32+ wks): 1 pt with pancreatic cancer and progression on 2 prior EGFR inhibitors had prolonged 32+ wk SD. There was 1 minor response (23.3%) in a pt with bevacizumab-refractory ovarian cancer (32+ wks). No CR or PR were seen. CONCLUSIONS: B + E + P at full doses has dose limiting toxicities of rash and mucositis. B 10 mg/kg q2wks + E 5 mg q48h + P 4.8 mg/kg q2wks is the maximum tolerated dose. This dose is currently being expanded in 20 patients with extensive pre- and on-treatment biomarker analyses. Updated clinical and biomarker data will be presented. [Table: see text] [Table: see text].

Duke Scholars

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

3551

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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MLA
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Howard, L. A., Bullock, K. E., Bendell, J. C., Uronis, H. E., Vlahovic, G., Blobe, G. C., … Hurwitz, H. I. (2009). Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors. J Clin Oncol, 27(15_suppl), 3551.
Howard, L. A., K. E. Bullock, J. C. Bendell, H. E. Uronis, G. Vlahovic, G. C. Blobe, R. F. Riedel, A. B. Nixon, J. P. Gockerman, and H. I. Hurwitz. “Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors.J Clin Oncol 27, no. 15_suppl (May 20, 2009): 3551.
Howard LA, Bullock KE, Bendell JC, Uronis HE, Vlahovic G, Blobe GC, et al. Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors. J Clin Oncol. 2009 May 20;27(15_suppl):3551.
Howard, L. A., et al. “Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors.J Clin Oncol, vol. 27, no. 15_suppl, May 2009, p. 3551.
Howard LA, Bullock KE, Bendell JC, Uronis HE, Vlahovic G, Blobe GC, Riedel RF, Nixon AB, Gockerman JP, Hurwitz HI. Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors. J Clin Oncol. 2009 May 20;27(15_suppl):3551.

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

3551

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences