Efficacy of apatinib in advanced hepatocellular carcinoma with lung metastasis: a retrospective, multicenter study.

Purpose: Lung is the most common extrahepatic metastatic site for patients with advanced hepatocellular carcinoma (HCC) and has a worse prognosis than intrahepatic metastasis. Apatinib is a receptor tyrosine kinase inhibitor that is promising for HCC treatment. We investigated whether apatinib is particularly effective for advanced HCC with lung metastasis. Methods: Sixty-one study patients with advanced HCC treated with apatinib seen at three different institutions between 2015 and 2018 were identified by retrospective review. Forty-one had lung metastasis (13 multi-organ metastasis and 28 lung metastasis only). Twenty had non-lung metastasis. Treatment consisted of oral apatinib 500 mg once daily. Response was assessed by imaging. The primary endpoint was metastasis-specific (m) progression-free survival (mPFS), for which only progression of metastatic lesions was assessed. Results: Median PFS was 3.37 months (range, 0.6-16.1) for all 61 patients. Objective response (OR) was achieved in 7/61 (11.6%) patients. For the 41 patients with lung metastasis, the median mPFS was 5 months (range, 0.9-21.9), with a mOR rate (mORR) of 22.0% (9/41). The mPFS of the 28 patients with only lung metastasis was better (hazard ratio/HR=0.316; 95% confidence interval/CI=0.144-0.696; log-rank p<0.001) than for the 20 with non-lung metastasis; comparison of the mORR showed similar results (21.4 vs. 5%; p=0.019). For the 13 patients with multi-organ metastasis, the mORR of lung lesions was marginally higher than that of other metastatic lesions (23.1 vs. 0%; p=0.096). Conclusions: Apatinib showed promising therapeutic effects on advanced HCC with lung metastasis, highlighting a population that could benefit preferentially from this treatment.