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

Int J Clin Oncol. 2021 Jul;26(7):1238-1247. doi: 10.1007/s10147-021-01902-2. Epub 2021 Apr 29.


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.

Keywords: Anti-EGFR antibody; Oral nucleoside anti-tumour agent; Outcomes; Phase 1/2 clinical trial; Salvage line.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Colorectal Neoplasms* / drug therapy
  • Humans
  • Panitumumab
  • Pyrrolidines
  • Thymine
  • Trifluridine* / adverse effects


  • Pyrrolidines
  • Panitumumab
  • tipiracil
  • Thymine
  • Trifluridine