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. (April 2021)

• Record Type: Journal Article
• Authors: Adkins, Douglas; Ley, Jessica; Atiq, Omar; Powell, Steven; Spanos, William C.; Gitau, Mark; Rigden, Caron; Palka, Kevin; Liu, Jingxia; Oppelt, Peter
• Is Part Of: Oral oncology. Volume 115(2021)
• Publication Date: 2021-04
• Subjects: Nab-paclitaxel -- Cetuximab -- Carboplatin -- Head and neck squamous-cell carcinoma -- Recurrent disease -- Metastatic disease; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2020.105173
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: 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). Abstract: Objectives: 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). Materials and methods: 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). Results: 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. Conclusion: 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.