In patients with previously treated advanced non-small cell lung cancer (NSCLC), anlotinib increases progression-free survival in squamous cell carcinoma (SCC) and improves both overall and progression-free survival in adenocarcinoma, according to a subgroup analysis of a phase 3 trial.
Treatment selection for NSCLC has become largely dependent on histological subtype. In the ALTER0303 trial, anlotinib, a multitargeted tyrosine kinase inhibitor (TKI), showed significant survival benefits among patients with recurrent or metastatic NSCLC previously treated with two or more lines of chemotherapy or a TKI. However, the efficacy of anlotinib in patients with histological subtypes had not yet been investigated. In a subgroup analysis of the trial, a team of researchers led by first author Ying Cheng, MD, of the Department of Thoracic Oncology at Jilin Cancer Hospital in Changchung, China, evaluated the efficacy and safety of anlotinib in patients with adenocarcinoma and SCC, the two most common histological subtypes of NSCLC.
A randomized, open-label trial, ALTER0303 enrolled 437 patients with previously treated advanced NSCLC, including 336 patients with adenocarcinoma and 86 patients with SCC. Nearly 40% of patients with adenocarcinoma and 9.3% of patients with SCC had an epidermal growth factor receptor (EGFR) mutation. Patients were randomized in a 2:1 ratio to receive 12 mg/day of oral anlotinib or placebo from days 1 to 14 of a 21-day cycle, until disease progression or unacceptable toxicity. The primary end point was overall survival, with secondary end points of progression-free survival, objective response rate, disease control rate, and quality of life.
Among patients with adenocarcinoma, anlotinib significantly prolonged median overall survival compared with placebo (9.6 months vs 6.9 months), as well as progression-free survival (5.5 months vs 1.4 months). The greatest overall survival benefit was seen in patients with an EGFR mutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 1, and three or more metastases. Anlotinib also increased progression-free survival among patients with SCC compared with placebo (4.8 months vs 2.7 months). While overall survival was prolonged in SCC, the difference did not reach statistical significance. Safety and tolerability were similar among patients with adenocarcinoma and SCC.
"Anlotinib improved overall survival in adenocarcinoma patients treated with at least two lines of chemotherapy or a TKI. SCC patients who received anlotinib experienced a significant improvement in progression-free survival and a tendency to experience prolonged overall survival," conclude Dr. Cheng and colleagues in their analysis, now published in Cancer Medicine. "Anlotinib should be considered an appropriate option for difficult-to-treat NSCLC patients as a subsequent treatment regardless of the histological type."
For More Information
Cheng Y, Han B, Li K, et al (2020). Effect of anlotinib as a third- or further-line therapy in advanced non-small cell lung cancer patients with different histologic types: subgroup analysis in the ALTER0303 trial. Cancer Med. [Epub ahead of print] DOI:10.1002/cam4.2913
Han B, Li K, Wang Q, et al (2018). Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: the ALTER0303 phase 3 randomized clinical trial. JAMA Oncol, 4(11):1569-1575. DOI:10.1001/jamaoncol.2018.3039
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