Axitinib Plus Avelumab Yields Some Responses in Adenoid Cystic Carcinoma

Treatment with the VEGFR inhibitor axitinib (Inlyta) and avelumab (Bavencio) yielded clinical activity in a cohort of patients with recurrent/metastatic adenoid cystic carcinoma (ACC), according to findings from a phase 2 trial (NCT03990571) published in the Journal of Clinical Oncology.

“The potential added benefit of avelumab to axitinib [in adenoid cystic carcinoma] should be further validated," according to the study authors.

In an evaluable population of 28 patients, the confirmed objective response rate (ORR) was 18.0% (95% CI, 6.1%-36.9%) comprising 5 partial responses (PRs); there was also an additional unconfirmed PR. Two of these PRs occurred after 6 months, yielding an ORR of 14% (95% CI, 4.0%-32.7%) at that time point.

With a median follow-up of 22 months (95% CI, 16.6-39.1), investigators reported a median progression-free survival (PFS) of 7.3 months (95% CI, 3.7-11.2) and a 6-month PFS rate of 57% (95% CI, 41%-78%). Additionally, the median overall survival (OS) was 16.6 months (95% CI, 12.4-not reached [NR]).

“Patients with refractory/metastatic ACC have few therapeutic options. VEGFR inhibitors have modest activity in ACC, mostly rendering disease stabilization,” the investigators wrote. “The premise of this study was that the VEGFR inhibitor axitinib would increase T-cell tumor infiltration and that combination treatment with avelumab would improve the efficacy over what has been reported with axitinib alone.”

This single-arm, open-label trial enrolled 40 patients between July 24, 2019, and June 29, 2021, 6 of whom did not meet the screening criteria. In the population of 36 patients who were given at least 1 dose of either agent, 6 patients were given less than 6 weeks of treatment with axitinib and did not undergo the first restaging imaging assessment because of loss of insurance (n = 3), logistic issues related to the COVID-19 pandemic (n = 2), an inability to swallow pills, or uncontrolled preexisting hypertension (n = 1).

Patients received oral axitinib at 5 mg twice a day along with 10 mg/kg of intravenous avelumab on days 1 and 15 of 28-day cycles. The axitinib dose could be reduced to 3 mg and 2 mg twice daily in the case of grade 3/4 adverse effects (AEs) or intolerable grade 2 AEs related to the drug. No avelumab dose reductions were permitted.

The primary end point of the trial was ORR per RECIST v1.1 criteria. Secondary end points included PFS, OS, and toxicity.

Patients 18 years or older with histologically confirmed recurrent or metastatic ACC, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function were eligible for enrollment on the trial.

The median patient age was 58 years (range, 29-88). Among the evaluable patients, 39% had histology with a solid component and 39% had received at least 1 prior line of palliative systemic therapy. The population was mostly female (57%) and White (57%).

The most common primary disease site was the minor salivary gland (50%) followed by the major salivary gland (39%) and the lacrimal gland (11%). Eighty-five percent of patients had metastatic disease and the most common metastases site was the lung (81%).

A total of 50% of patients achieved stable disease, leading to a disease control rate (DCR) of 71% (95% CI, 51.3%-86.8%). The DCR at 6 months was 57% (95% CI, 37.2%-75.5%). A further 29% developed progressive disease as their best overall response.

The median duration of response (DOR) for the 6 patients who responded was 5.5 months (95% CI, 3.7-NR); for the 5 patients who achieved a confirmed PR, the median DOR was 11 months (95% CI, 5.5-NR).

The safety analysis included 34 patients. The most frequent treatment-related AEs (TRAEs) were fatigue (62%), hypertension (32%), and diarrhea (32%). In sum, 14 grade 3 TRAEs occurred in 10 patients and included hypertension (9%), fatigue (6%), deep vein thrombosis (6%), and palmarplantar erythrodysesthesia (6%). No grade 4 or 5 TRAEs occurred.

Investigators reported that 12% of patients discontinued avelumab, including 3 due to grade 2 fatigue and 1 due to grade 3 hepatitis. Nine patients underwent axitinib dose reductions due to either fatigue (n = 4), palmarplantar erythrodysesthesia (n = 3), hypertension (n = 1), or weight loss (n = 1). Three patients had 2 dose reductions because of diarrhea, weight loss, and fatigue. A single patient discontinued axitinib due to persistent fatigue.

“The results reported herein—with axitinib plus avelumab conferring a confirmed ORR of 18%—compare favorably with response rates reported for axitinib or PD-1 inhibitors as monotherapy in ACC,” the investigators concluded. “The potential added benefit of avelumab to axitinib should be further validated.”

Reference

Ferrarotto R, Sousa LG, Feng L, et al. Phase II clinical trial of axitinib and avelumab in patients with recurrent/metastatic adenoid cystic carcinoma. J Clin Oncol. Published online March 10, 2023. doi: 10.1200/JCO.22.02221