Despite Poor Prognosis, Anlotinib May Improve PFS in Pre-Treated NSCLC With Liver Metastases in Later Lines

Despite having worse outcomes than patients with no liver metastases, patients with pretreated non–small cell lung cancer with liver metastases may benefit from anlotinib as a third-line or later therapy, according to data from the phase 3 ALTER 0303 trial (NCT02388919) published in the Journal of Cancer Research and Clinical Oncology.

A longer median PFS of 3.0 months (95% CI, 2.0-3.9) was observed with anlotinib vs 0.9 months (95% CI, 0.7-1.1) with placebo (HR, 0.23; 95% CI, 0.12-0.42; P <.0001). The median overall survival (OS) in the anlotinib group was 6.6 months (95% CI, 5.3-7.9) compared 4.0 months (95% CI, 2.2-5.8) in the placebo arm (HR, 0.61; 95% CI, 0.36-1.02; P = .055).

Overall, those without liver metastases had superior PFS of 4.2 months (95% CI, 3.9-4.5) in the anlotinib group vs 2.6 months (95% CI, 2.0-3.3) in the placebo group (HR, 1.83; 95% CI, 1.39-2.41; P <.0001), and a longer median OS of 9.4 months (95% CI, 8.5-10.4) vs 5.6 months (95% CI, 4.3-7.0; HR, 1.92; 95% CI, 1.46-2.53; P <.0001).

A total of 68.4% of patients in the placebo group and 60.3% in the anlotinib group who did not have liver metastases died at data cutoff. In the anlotinib group, the median PFS was 5.5 months (95% CI, 5.0-6.1) vs 1.4 months (95% CI, 1.2-1.6) in the placebo group (HR, 0.25; 95% CI, 0.19-0.33; P <.0001). The median OS in the anlotinib group for those without liver metastases was 10.1 months (95% CI, 8.8-11.4) vs 7.0 months (95% CI, 5.0-9.0) in the placebo group (HR, 0.69; 95% CI, 0.53-0.91; P = .008).

A total of 440 patients enrolled, of whom 437 were randomized and included in the efficacy analysis. Of these patients, 17.8% had liver metastases. Among individuals with liver metastases, 66.7% received anlotinib and 33.3% received placebo. Moreover, 3.8% of patients had liver metastases alone and 96.2% had more than 1 metastatic site. Additionally, 50 patients had over 3 metastases, 63 had adenocarcinoma, and 15 had squamous cell carcinoma. EGFR mutations were observed in 28.2% of patients and 1.3% had ALK mutations. A total of 39.7% of patients who had liver metastases received previous targeted therapy.

By data cutoff, 88.5% of patients with liver metastases in the placebo group and 82.7% in the anlotinib group had died. The objective response rate for those in the anlotinib group was 6.3% vs 0% in the placebo (P = .548), and the disease control rate was 77.1% vs 19.0% (P <.0005), respectively.

The univariate analysis showed similar outcomes for those with liver metastases and different tumor histologies with regard to both PFS (P = .841) and OS (P = .619). Investigators also reported that number of metastases was not predictive of PFS (P = .068) or OS outcomes (P = .198) outcomes. Additionally, EGFR mutations did not favor better survival in terms of PFS (P = .066) or OS (P = .694).

Subsequent treatment was given in 42.3% of patients in the anlotinib group vs 50% in the placebo group (P >.05) following disease progression. In total, 23.1% vs 30.8% of patients in either arm received chemotherapy, 17.3% vs 26.9% received targeted therapy, 9.6% vs 11.5% received radiotherapy, 3.8% vs 3.8% received traditional Chinese medicine, and 3.8% vs 0% received immunotherapy (all P >.05).

Treatment with anlotinib was more associated with hand-foot syndrome (7.7% vs 0%), serum thyroid-stimulating hormone rise (7.7% vs 3.8%), hypertension (3.8% vs 3.8%), prolongation of QTc interval (3.8% vs 3.8%) vs the placebo group.; adverse effects (AEs) did not differ significantly between groups (P >.05), with the aforementioned AEs being no more than grade 3.

Reference

Shen Y, Lu J, Hu F, et al. Effect and outcomes analysis of anlotinib in non-small cell lung cancer patients with liver metastasis: results from the ALTER 0303 phase 3 randomized clinical trial. J Cancer Res Clin Oncol. Published online April 28, 2022. doi:10.1007/s00432-022-03964-9