Phase II Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma

Abstract

PURPOSE We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC). PATIENTS AND METHODS Eligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; ≥4 responses in 29 patients would reject the null hypothesis. RESULTS Forty patients enrolled from July 2019 to June 2021; 28 were evaluable for efficacy (six screen failures; six evaluable for safety only). The confirmed ORR was 18% (95% CI, 6.1 to 36.9); there was one unconfirmed partial response (PR). Two patients achieved PR after 6 months; thus, the ORR at 6 months was 14%. The median follow-up time for surviving patients was 22 months (95% CI, 16.6 to 39.1 months). The median PFS was 7.3 months (95% CI, 3.7 to 11.2 months), 6-month PFS rate was 57% (95% CI, 41 to 78), and median OS was 16.6 months (95% CI, 12.4 to not reached months). Most common treatment-related adverse events (TRAEs) included fatigue (62%), hypertension (32%), and diarrhea (32%). Ten (29%) patients had serious TRAEs, all grade 3; four patients (12%) discontinued avelumab, and nine patients (26%) underwent axitinib dose reduction. CONCLUSION The study reached its primary end point with ≥4 PRs in 28 evaluable patients (confirmed ORR of 18%). The potential added benefit of avelumab to axitinib in ACC requires further investigation.

Vascular Endothelial Growth Factor Receptor Inhibitors for Recurrent or Metastatic Adenoid Cystic Carcinoma

“…Given the difficulty in distinguishing between ACC disease stability and drug-induced stability, the results of this RCT are strong evidence that axitinib delays ACC progression . Of note, while our meta-analysis looked exclusively at VEGFR inhibitors as single agent, a 2023 trial of combination of axitinib plus the programmed death-ligand 1 inhibitor avelumab showed positive outcomes, garnering inclusion in the updated NCCN guidelines…”

Adenoid cystic carcinoma of the retromolar pad region: A case report

“…Therefore, cylindromas with malignant behavior are referred to as adenoid cystic carcinoma (ACC) to accurately describe their pathological features and clinical manifestations. Today, ACC is the most common term for the lesion [ 21 ]. As one of the most common epithelial malignant tumors of the salivary glands, ACC is highly invasive and neurophilic, easily infiltrates blood vessels, and rarely spreads to the lymph nodes [ 22 ].…”

The Efficacy of Immunotherapy and Clinical Utility of Comprehensive Genomic Profiling in Adenoid Cystic Carcinoma of Head and Neck

“…Intriguingly, a recent study showed that MYB is essential for the development of precursors of exhausted T cells, and the response to PD-1 checkpoint inhibition depends on MYB expression [35], which is consistent with our results. Furthermore, very recently, the addition of the PD-L1 inhibitor avelumab to axitinib has been shown to be beneficial in ACC of the head and neck [36], leading to its inclusion as a therapeutic option for ACC in the National Comprehensive Cancer Network guidelines.…”