The impact of previous therapy strategy on the efficiency of anlotinib hydrochloride as a third-line treatment on patients with advanced non-small cell lung cancer (NSCLC): a subgroup analysis of ALTER0303 trial

Abstract

Background: Lung cancer remains one of the deadliest cancers worldwide. The ALTER0303 trial revealed that anlotinib might be used as a third-line or further treatment in non-small cell lung cancer (NSCLC) patients. Meanwhile, the impact of previous therapy strategies on the efficiency of anlotinib still remains unknown. Methods:The subgroup of patients in ALTER0303 were analyzed by using Kaplan-Meier estimates, Pearson χ 2 , or Fisher's exact test.Results: There was no statistical significance on progression-free survival (PFS) and overall survival (OS) among patients in different previous antiangiogenic treatments groups. Patients in the chest radiotherapy (CRT) group had longer median PFS than the non-CRT group (5.93 vs. 4.63 m, P=0.027). Regardless of what kind of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) and chemotherapy regimens were used previously, all patients gained longer PFS in the anlotinib group, while only patients treated with vinorelbine/platinum in the EGFR wild type group, pemetrexed/platinum, vinorelbine/ platinum, and gefitinib in the EGFR mutation group, and EGFR TKI used as the first line group could benefit from anlotinib on OS. When the OS was calculated from the time of diagnosis to the death, anlotinib could have increased median OS about 6 months (33.8 vs. 27.8 m, P<0.001) compared to the placebo with a hazard ratio (HR) (95% CI): 0.77 (0.60, 1.00).Conclusions: This study indicated that previous bevacizumab or endostatin treatments had no impact on the efficiency of anlotinib. Patients with CRT history benefited more from anlotinib on PFS. EGFR TKI and chemotherapy treatment history had more impact on OS than PFS in patients treated with anlotinib compared to placebo.

Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

“…A total of 437 advanced NSCLC patients were included in the trial, and were randomly allocated into the placebo group (n = 143) or the anlotinib group (n = 294) at a ratio of 1:2. These results showed that anlotinib prolonged the mOS by 3.3 months (9.6 vs 6.3 months, HR 0.68, 95% CI 0.54-0.87, p = 0.0018) and the mPFS by 4.0 months (5.4 vs 1.4 months, HR 0.25, 95% CI 0.19-0.31, p < 0.0001) (27)(28)(29). In the ALTER0303 trial, the e cacy of anlotinib for the treatment of BM was also evaluated, as 97 (22.2%) patients had BM at baseline.…”

“…The patients in the anlotinib group had a longer time to brain progression (TTBP) than the placebo group, indicating that anlotinib delays the progression of intracranial lesions from advanced NSCLC patients (30). The exploratory subgroup analysis of the ALTER0303 trials showed that patients with either EGFR gene mutation or wild-type exhibited improved PFS and OS with anlotinib treatment (27,28,30). Related clinical studies show that both NSCLC and SCLC can signi cantly prolong PFS and OS (25)(26)(27)(28)30).…”

“…The exploratory subgroup analysis of the ALTER0303 trials showed that patients with either EGFR gene mutation or wild-type exhibited improved PFS and OS with anlotinib treatment (27,28,30). Related clinical studies show that both NSCLC and SCLC can signi cantly prolong PFS and OS (25)(26)(27)(28)30). Therefore, in May 2018 and June 2019, China Food and Drug Administration (CFDA) o cially approved anlotinib for single drug treatment for the third-line or higher treatment of advanced NSCLC patients and SCLC patients with nongene mutation or EGFR/ALK-TKIs resistance.…”

“…Clinical studies have con rmed that anlotinib can effectively treat some patients with advanced lung cancer, including patients with BM (27,28,30). However, for NSCLC patients with no gene mutation or EGFR/ALK-TKIs resistance, as well as SCLC patients with BM, cranial radiotherapy (CRT) is still considered the standard treatment regime, as this treatment can quickly relieve central nervous system the symptoms and improve the survival time of patients (31).…”

<p>Association of TP53 Mutations with Response to Anlotinib Treatment in Advanced Non-Small Cell Lung Cancer</p>

“…5 Recently, a number of studies have introduced some predictors of response to anlotinib treatment. 6,8 Unfortunately, to date, no predictors available has yet been identified to predict the response to antiangiogenic drug anlotinib.…”