Multicenter Single-Arm, Two-Stage Phase 2 Study of Panitumumab in Patients With Cetuximab-Refractory Metastatic Colorectal Cancer: The PACER Trial

Maria Carmela Piccirillo, Antonio Avallone, Chiara Carlomagno, Evaristo Maiello, Gerardo Rosati, Oscar Alabiso, Guglielmo Nasti, Sabino De Placido, Tizana Pia Latiano, Domenico Bilancia, Alessandro Ottaiano, Alfonso De Stefano, Carmela Romano, Lucrezia Silvestro, Anna Nappi, Antonino Cassata, Pasqualina Giordano, Rosario Vincenzo Iaffaioli, Nicola Normanno, Francesco PerroneBruno Daniele

Research output: Contribution to journalArticle

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. PACER is a phase 2 study aiming to assess whether panitumumab monotherapy is active in patients with cetuximab-refractory metastatic colorectal cancer. Primary end point was 2-month progression-free rate. According to a minimax two-stage design, 28 and 41 patients were required at the two stages, respectively. Panitumumab was shown to be not active at the second stage. The study failed to demonstrate the experimental hypothesis.

Original languageEnglish
JournalClinical Colorectal Cancer
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Biomarker
  • EGFR
  • RAS
  • Resistance
  • Response

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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