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.

Trial registration: ClinicalTrials.gov NCT03990571.

FIG 1.

Study flow chart diagram. IRB, Institutional Review Board

FIG 2.

Efficacy outcomes. (A) Waterfall plot demonstrating maximum percent change in the sum of target lesions from baseline according to RECIST 1.1; each bar represents a patient. (B) Spider plot illustrating longitudinal percentage change in tumor size from baseline according to RECIST 1.1; each line represents a patient. (C) Illustrative computed tomography scans of two patients who achieved a partial response; red arrows and circles highlight metastatic tumor regions. PD, progressive disease; PR, partial response; SD, stable disease.

FIG 3.

Kaplan-Meier curves for (A) PFS and (B) OS. OS, overall survival; PFS, progression-free survival.

FIG A1.

Genomic analysis of evaluable patients (N = 23).

FIG A2.

Kaplan-Meier curves for (A) PFS and (B) OS according to NOTCH1 mutational status (y = NOTCH1 mutant; n = NOTCH1 wild type; E = event, progression or death; N = number of patients at risk). OS, overall survival; PFS, progression‐free survival.