Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma

Abstract

Adenoid cystic carcinoma (ACC) is a rare cancer of secretory glands. Recurrent or metastatic (R/M) ACC is generally considered resistant to cytotoxic chemotherapy. Recent phase II studies have reported improved objective response rates (ORR) with the use of the multi-kinase inhibitor lenvatinib. We sought to evaluate real-world experience of R/M ACC patients treated with lenvatinib monotherapy within the UK National Health Service (NHS) to determine the response rates by Response Evaluation Criteria of Solid Tumour (RECIST) and clinical outcomes. Twenty-three R/M ACC patients from eleven cancer centres were included. All treatment assessments for clinical decision making related to drug therapy were undertaken at the local oncology centre. Central radiology review was performed by an independent clinical trial radiologist and blinded to the clinical decision making. In contrast to previously reported ORR of 12-15%, complete or partial response was not observed in any patients. Eleven patients (52.4%) had stable disease and 5 patients (23.8%) had progression of disease as the best overall response. The median time on treatment was 4 months and the median survival from discontinuation was 1 month. The median PFS and OS from treatment initiation were 4.5 months and 12 months respectively. Multicentre collaborative studies such as this are required to evaluate rare cancers with no recommended standard of care therapy and variable disease courses.

Keywords: adenoid cystic carcinoma; lenvatinib; salivary gland cancer.

Figure 1

(A) Waterfall plot of maximum percent change in tumour size from baseline as measured by Response Evaluation Criteria in Solid Tumour (RECIST). The upper dotted line represents the threshold for progressive disease (a 20% increase in the sum of the longest diameter of the target lesions) and the lower dotted line represents the threshold for partial response (a 30% decrease in the sum of the longest diameter of the target lesions). (B) Change from the baseline (%) in the sum of the target lesions over time. Red lines represent patients on a starting dose of 24 mg. Black lines represent patients starting on a reduced dose. (C) Swimmers plot of time from the start of lenvatinib to the time of discontinuation (blue bar) and survival from discontinuation to death or last follow-up (orange bar). Each bar represents an individual patient, with the length of the bar corresponding to the time of overall survival. Arrow indicates patient is alive.

Figure 2

Change in the sum of target lesions over time (mm). (A) Patients initiated on lenvatinib 24 mg once daily. (B) Patients initiated on lenvatinib 20 mg once daily. (C) Patients initiated on lenvatinib 18 mg and 14 mg once daily. The Y axes are standardized using axis breaks to evaluate a 100 mm change in the measurements for comparison of the magnitude of change between patients. Individual patients are labelled i–viii.

Figure 3

Kaplan–Meier estimate for (A) Progression free survival on lenvatinib, defined as time from first dose until objective disease progression; (B) Overall survival from initiation of lenvatinib, defined as time from first dose to death from any cause; dashes indicate censored events.

Figure 4

Kaplan–Meier estimate for overall survival in patients with or without (A) TP53 mutation, (B) NOTCH1 mutation and (C) TERT mutation. mOS = median overall survival; mut = mutant; wt = wild type.