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

• Published in: International journal of clinical oncology Vol. 26; no. 7; pp. 1238 - 1247
• Main Authors: Kato, Takeshi, Kagawa, Yoshinori, Kuboki, Yasutoshi, Gamoh, Makio, Komatsu, Yoshito, Yasui, Hirofumi, Satake, Hironaga, Oki, Eiji, Tanioka, Hiroaki, Kotaka, Masahito, Makiyama, Akitaka, Denda, Tadamichi, Goto, Masahiro, Yoshino, Takayuki, Yamazaki, Kentaro, Soeda, Junpei, Shibuya, Kazunori, Iwata, Masaru, Oba, Koji, Yamaguchi, Kensei
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.07.2021; Springer Nature B.V
• Subjects: Adverse events; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antiviral drugs; Cancer Research; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Disease control; Dosage; Epidermal growth factor; Frontotemporal dementia; Humans; Leukocytes (neutrophilic); Medicine; Medicine & Public Health; Metastases; Metastasis; Monoclonal antibodies; Oncology; Original; Original Article; Panitumumab; Pyrrolidines; Safety; Surgical Oncology; Targeted cancer therapy; Thymine; Trifluridine - adverse effects; Tumors; Oral nucleoside anti-tumour agent; Phase 1/2 clinical trial; Anti-EGFR antibody; Outcomes; Salvage line
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-021-01902-2

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/m 2 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.