Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

Takeshi Kato, Yoshinori Kagawa, Yasutoshi Kuboki, Makio Gamoh, Yoshito Komatsu, Hirofumi Yasui, Hironaga Satake, Eiji Oki, Hiroaki Tanioka, Masahito Kotaka, Akitaka Makiyama, Tadamichi Denda, Masahiro Goto, Takayuki Yoshino, Kentaro Yamazaki, Junpei Soeda, Kazunori Shibuya, Masaru Iwata, Koji Oba, Kensei Yamaguchi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods: APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results: Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion: Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

Original languageEnglish
Pages (from-to)1238-1247
Number of pages10
JournalInternational Journal of Clinical Oncology
Volume26
Issue number7
DOIs
Publication statusPublished - Jul 2021

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hematology
  • Oncology

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