1. Multicenter Single-Arm, Two-Stage Phase 2 Study of Panitumumab in Patients With Cetuximab-Refractory Metastatic Colorectal Cancer: The PACER Trial.
- Author
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Piccirillo MC, Avallone A, Carlomagno C, Maiello E, Rosati G, Alabiso O, Nasti G, De Placido S, Latiano TP, Bilancia D, Ottaiano A, De Stefano A, Romano C, Silvestro L, Nappi A, Cassata A, Giordano P, Iaffaioli RV, Normanno N, Perrone F, and Daniele B
- Subjects
- Aged, Cetuximab therapeutic use, Colorectal Neoplasms genetics, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Disease Progression, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Panitumumab adverse effects, Progression-Free Survival, Prospective Studies, Proto-Oncogene Proteins p21(ras) genetics, Cetuximab pharmacology, Colorectal Neoplasms drug therapy, Panitumumab administration & dosage
- Abstract
Purpose: To assess whether panitumumab is active in patients with cetuximab-refractory metastatic colorectal cancer (mCRC)., Patients and Methods: Eligible patients had pretreated RAS (renin-angiotensin system) wild-type mCRC that progressed after cetuximab treatment, after having shown either objective response or stable disease. A minimax two-stage design was applied, with progression-free rate at 2 months as the primary end point. At least 12 of 28 and 21 of 41 successes at the first and second stage, respectively, were required for a positive result. Panitumumab 6 mg/kg was provided every 2 weeks, until progression or unacceptable toxicity., Results: Overall, 52 patients with KRAS (Kirsten rat sarcoma viral oncogene) wild-type disease were enrolled, but 11 were found to have mutated disease after all-RAS retesting. Among 41 eligible patients, median time since diagnosis was 38 months, and 71% experienced an objective response to previous cetuximab. First stage was passed with 12 of 28 patients alive without progression at 2 months. At the second stage, 17 of 41 patients were alive without progression at 2 months. At a median follow-up of 21.8 months, 35 patients experienced disease progression, and 26 died. Median progression-free survival was 2.1 months (95% confidence interval, 1.8-3.6) and median overall survival 6.8 months (95% confidence interval, 4.6-16.6). Most of the patients experienced no adverse reactions; 25% of patients had grade 3 rash., Conclusion: According to our study design, panitumumab was not effective in patients with cetuximab-refractory RAS wild-type mCRC., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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