In:
The Oncologist, Oxford University Press (OUP), Vol. 22, No. 3 ( 2017-03-01), p. 243-e23
Abstract:
The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group. The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic KRAS mutant colorectal carcinoma. Background Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. Methods Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed. Results In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n = 84), FOLFIRI/simtuzumab 200 mg (n = 85), and FOLFIRI/placebo (n = 80). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI], p value versus placebo; 1.32 [0.92, 1.89] ; p = .10), 5.4 months (1.45 [1.01, 2.06]; p = .04), and 5.8 months. Median OS was 11.4 months (1.23 [0.80, 1.91] ; p = .25), 10.5 months (1.50 [0.98, 2.30]; p = .06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients. Conclusion The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC.
Type of Medium:
Online Resource
ISSN:
1083-7159
,
1549-490X
DOI:
10.1634/theoncologist.2016-0479
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2017
detail.hit.zdb_id:
2023829-0
Permalink