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*

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, ? = 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.