Promising long-term disease control and survival with pembrolizumab and cabozantinib for head and neck cancer

Long-term follow-up of a phase 2, single-arm study of the combination of pembrolizumab and cabozantinib for patients with recurrent or metastatic head and neck cancer showed encouraging tolerability of the regimen as well as disease control and overall survival (OS) at 2 years, according to a study published in Clinical Cancer Research.¹

At 22.4 months’ follow-up, the median progression-free survival (PFS) and OS were 12.8 and 27.7 months, respectively, with 2-year PFS and OS rates of 32.6% and 54.7%, respectively.

Previously reported findings of the study showed a median PFS of 14.6 months with a 1-year PFS rate of 54% and a median OS of 22.3 months with a 1-year OS rate of 68.4% at a median follow-up of 10.6 months.² The multicenter, open-label study included 36 patients with inoperable, recurrent, and/or metastatic head and neck cancer treated with the combination therapy, of which 33 were evaluable.

The long-term adverse events included hypothyroidism (5.5%) and grade 1 aspartate aminotransferase and alanine aminotransferase elevation (2.8%).

Lead author and principal investigator Nabil F. Saba, MD, professor and vice chair of the Department of Hematology and Medical Oncology and director of the Head and Neck Cancer Medical Oncology Program at the Winship Cancer Institute at Emory University, says that the results confirm the robust clinical activity of cabozantinib and pembrolizumab in head and neck squamous cell cancers. He notes the encouraging survival outcomes seen with longer follow-up, which indicated that the combination treatment is promising in this setting and merits further evaluation.

The updated results included an analysis of biomarkers that have implications for future patient selection for this combination or similar agents within these drug classifications (an anti–programmed cell death protein 1 inhibitor, such as pembrolizumab, with a vascular endothelial growth factor receptor tyrosine kinase inhibitor, such as cabozantinib). Based on baseline tissue samples obtained from patients’ tumors, a correlation between a higher density of CD8+, CD103+, and CSF-1R+ cells and improved OS was noted.

Dr Saba clarifies that these findings may suggest a possible innate immune mechanism of cabozantinib “given the function of CSF1-R in regulating tumor-associated macrophages, a known target of cabozantinib.”

Based on these results, a phase 2/3 trial (Stellar-305) comparing pembrolizumab and zanzalintinib with pembrolizumab and a placebo in the same patient population is underway and accruing patients in different countries. “Results from this trial are eagerly awaited, as it could potentially change the standard of care in this patient population,” says Dr Saba.

Commenting on the study, Aliyah Pabani, MD, MPH, an assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, calls the results promising and says they suggest that the combination may offer meaningful activity with a manageable safety profile compared to current standard treatments. However, she underscores the need for validation in phase 3 trials. “If confirmed in larger, randomized phase 3 trials, the combination of pembrolizumab and cabozantinib could become a potential treatment option for patients with recurrent and/or metastatic head and neck cancer,” she says.