Nanoparticle albumin-bound paclitaxel with cetuximab and carboplatin as first-line therapy for recurrent or metastatic head and neck cancer: A single-arm, multicenter, phase 2 trial

• Published in: Oral oncology 2021-04, Vol.115, p.105173-105173, Article 105173
• Main Authors: Adkins, Douglas, Ley, Jessica, Atiq, Omar, Powell, Steven, Spanos, William C., Gitau, Mark, Rigden, Caron, Palka, Kevin, Liu, Jingxia, Oppelt, Peter
• Format: Article
• Language: English
• Subjects: Aged; Albumins - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Carboplatin; Carboplatin - administration & dosage; Cetuximab; Cetuximab - administration & dosage; Female; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Head and neck squamous-cell carcinoma; Humans; Male; Metastatic disease; Middle Aged; Nab-paclitaxel; Nanoparticles - therapeutic use; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Paclitaxel - administration & dosage; Recurrent disease
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2020.105173

•The median PFS with CACTUX was similar to historical EXTREME (6.1 vs 5.6 months).•The ORR with CACTUX was 60%, and the CR rate was 17% (EXTREME: 36% and 3%).•The median OS with CACTUX was 17.8 months (EXTREME: 10.1 months). Macropinocytosis promotes internalization of albumin into cells to serve as a nutrient supply and is constitutively driven by signaling pathways frequently hyperactivated in head and neck squamous-cell carcinoma (HNSCC). In this way, drugs bound to albumin may selectively target HNSCC. nab-paclitaxel is a nanoparticle albumin-bound formulation of paclitaxel that improves drug delivery into tumor compared to paclitaxel. The primary aim of this single-arm, multicenter, phase 2 trial was to determine if nab-paclitaxel, cetuximab, and carboplatin (CACTUX regimen) would result in longer progression-free survival (PFS) than the historical regimen (EXTREME: 5-fluorouracil, cetuximab, and a platinum). Patients with untreated recurrent or metastatic HNSCC received six, three-week cycles of nab-paclitaxel, cetuximab, and carboplatin, followed by maintenance nab-paclitaxel and cetuximab until progression. We hypothesized the median PFS with CACTUX would be 35% longer than with EXTREME (corresponding to 7.6 vs 5.6 months; power 0.80, α = 0.05, one-sided test, n = 70). Secondary outcomes included objective response rate (ORR) and overall survival (OS). Seventy-four patients enrolled into the trial; seventy were evaluable. The median PFS was 6.1 months (95% CI, 4.1–7.4). The ORR was 60%. Median follow-up was 18 months (IQR: 4.7–23). The median OS was 17.8 months (95% CI, 8.5–21.7) for all patients, and 19.8 months (95% CI, 10.9–22.0) for human papillomavirus (HPV)-related oropharynx SCC and 14.0 months (95% CI, 4.6–23.3) for HPV-unrelated HNSCC. Among patients with recurrent or metastatic HNSCC, CACTUX did not result in a longer PFS than historical EXTREME. However, CACTUX did result in a more favorable ORR and OS.