Axitinib prolongs PFS in metastatic adenoid cystic carcinoma
Axitinib significantly extended PFS among patients with recurred or metastatic adenoid cystic carcinoma, according to results of a randomized phase 2 study presented during the ASCO20 Virtual Scientific Program.
“Adenoid cystic carcinoma arises from the salivary gland with a broad spectrum of disease course that has a low response to cytotoxic chemotherapy and targeted agents,” Bhumsuk Keam, MD, PhD, medical oncologist at Seoul National University Hospital in Seoul, South Korea, said during a presentation. “The role of anti-angiogenic agents has been evaluated in single-arm phase 2 trials. However, the role of chemotherapy is still controversial, because of natural stable disease course without chemotherapy. Therefore, a randomized trial is absolutely needed.”
Keam and colleagues conducted the multicenter, prospective, open-label trial to evaluate the efficacy of axitinib, a small molecule tyrosine kinase inhibitor, compared with observation among 57 patients (median age, 56 years; range, 26-77; 53.3% women) with recurred or metastatic adenoid cystic carcinoma who progressed within 9 months. Three-quarters of patients had an ECOG performance status of 1.
Researchers randomly assigned patients 1:1 to 5 mg twice-daily axitinib (Inlyta, Pfizer) or observation, with permission for patients in the observation group to cross over to the treatment group if their disease progressed.
Researchers assessed treatment response every 8 weeks per RECIST version 1.1 and safety per NCI-Common Terminology Criteria for Adverse Events version 4.0.
Six-month PFS served as the primary endpoint. Secondary endpoints included objective response rate, OS, PFS, duration of response and adverse events.
Median follow-up was 25.4 months.
Results showed a 6-month PFS rate of 73.2% (95% CI, 54.8-88.1) with axitinib vs. 23.2% (95% CI, 9.3-41.1) with observation (HR = 0.19; 95% CI, 0.08-0.45).
Median PFS was 10.8 months with axitinib vs. 2.8 months with observation (HR = 0.25; 95% CI, 0.14-0.48). The ORR was 3.3% (95% CI, 0.1-17.2) with axitinib vs. 0% (95% CI, 0-12.8) with observation.
Disease control rates were 100% (95% CI, 88.4-100) in the axitinib group vs. 51.9% (95% CI, 32-71.3) in the observation group.
Among the 26 patients who crossed over from observation to the axitinib group, the ORR was 11.5%. Median OS was 27.2 months (95% CI, 20.2-32.8) in the observation group vs. not reached in the axitinib group (HR = 0.6; 95% CI, 0.26-1.38).
Common grade 1 to grade 2 adverse events in the axitinib group included oral mucositis and fatigue.
Results of an analysis using pre-axitinib tissue samples of 28 patients showed common mutations, including ARID1B (28.6%), KDM6A and PARP4 (21.4%) and NOTCH1, MLL2, MLL3 and SFB1 (7.8%). Researchers noted that mutation burden or any specific mutation did not correlate with response or PFS.
“In this first-ever randomized trial in patients with recurred or metastatic adenoid cystic carcinoma, axitinib showed significantly increased 6-month PFS compared with observation and toxicity was overall well-tolerated,” Keam said. “Axitinib is a promising option to control adenoid cystic carcinoma disease progression and a randomized, prospective, phase 3 trial is warranted.” – by Jennifer Southall
Reference:
Keam B, et al. Abstract 6503. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
Disclosures: Adenoid Cystic Carcinoma Research Foundation supported this study. Keam reports consultant/advisory roles with ABL Bio, AstraZeneca, Cellid, Genexin and MSD Oncology; and research funding from AstraZeneca, MSD Oncology and Ono Pharmaceutical. Please see the abstract for all other researchers’ relevant financial disclosures.
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Keam B, et al. Abstract 6503. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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