Axitinib Extends PFS For Recurrent, Metastatic Adenoid Cystic Carcinoma

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The multikinase inhibitor axitinib may improve progression-free survival (PFS) for patients with recurrent or metastatic adenoid cystic carcinoma (ACC) compared with observation, suggest phase II trial results presented at the virtual 2020 ASCO Annual Meeting. 

Investigator Bhumsuk Keam, from Seoul National University Hospital in South Korea, explained that this first randomised trial for ACC was necessary to confirm findings from earlier single-arm studies because the “slow-growing nature” of the tumour means that “it is difficult to distinguish active disease controlled by the chemotherapy from the natural stable disease without chemotherapy.” 

The trial included patients aged a median 56 years with unresectable locoregional or metastatic disease who had progressed within the past 9 months, regardless of whether they had received prior systemic therapy. 

The primary endpoint of PFS at 6 months was achieved by 73% of the 27 patients randomly assigned to receive axitinib 5 mg twice daily versus 23% of the 27 patients who instead received only observation. The median PFS in the two groups was 10.8 and 2.8 months, respectively, giving a significant hazard ratio (HR) for progression or death of 0.25. 

The secondary endpoint of median overall survival (OS) was unreached in the axitinib-treated patients versus 27.2 months in the observation group after a median follow-up of 31.9 and 28.4 months, respectively, giving a nonsignificant HR for death of 0.60.  

Bhumsuk Keam suggested that OS may not have differed significantly between the treatment arms because patients in the observation arm were permitted to cross over to axitinib therapy at time of progression. 

None of the patients in the axitinib or observation arms achieved a complete or partial response to treatment, but stable disease was reported for 100% and 51.9% of the groups, respectively. And three of the 26 patients who crossed over to axitinib therapy on progression experienced a partial response to treatment, giving an objective response rate of 11.5%. 

Next-generation sequencing was performed on pre-axitinib tissue samples from 28 patients and this showed that “the mutational burden was relatively low, and this finding was pretty compatible with the previous reports”, the investigator said. There was no correlation identified between detected mutations and patient outcomes. 

Discussing the safety profile, the presenter said that the most common adverse events were those previously reported for anti-angiogenic agents, namely stomatitis, anorexia, fatigue, hypertension and proteinuria. Events mostly occurred at grade 1 or 2, with hypertension the most common grade 3–4 event (23.3 vs 0.0% controls). 

“Toxicity was […] well tolerated and manageable, and axitinib is a promising option for controlling ACC disease progression”, Bhumsuk Keam summarised, adding that a phase III trial is now warranted. 

Reference  

Keam B, Kang EJ, Ahn M-J, et al. Randomized phase II study of axitinib versus observation in patients with recurred or metastatic adenoid cystic carcinoma. J Clin Oncol; 38: suppl; abstr 6503. DOI: 10.1200/JCO.2020.38.15_suppl.6503.