Anlotinib plus docetaxel versus docetaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC): Updated results from a phase I/II study.
Authors: Fang Yong , Pan Hongming , Shou Jiawei , Hong Wei , Guo Qunyi , Yang Xinmei , Zhu Dan , Chen Jun , Lu Liqin , Rao Chuangzhou , Lan Fen 
Published: June 2021

e21055 Background: Second-line chemotherapy alone, such as docetaxel, is standard of care for patients (pts) with advanced NSCLC, but the efficacy is poor. Anti-angiogenic drugs plus chemotherapy had shown to significantly prolong progression-free survival (PFS) in advanced NSCLC (REVEL and LUME-LUNG1). The REVEL trial had demonstrated that East Asian pts with advanced NSCLC receiving docetaxel (60 mg/m2, not 75mg/m2) and ramucirumab had a better safety profile. Anlotinib, a novel oral multitarget tyrosine kinase inhibitor, significantly improved PFS and overall survival (OS) of advanced NSCLC in the ALTER0303 trial. In the phase I study, 10mg (QD, d1 to 14 of a 21-day cycle) was identified as the maximum tolerated dose (MTD) of anlotinib when combined with docetaxel (60mg/m2) by a 3+3 dose de-escalation exploration. Here, we presented the updated efficacy and safety of anlotinib plus docetaxel versus docetaxel as second-line treatment for driver-negative advanced NSCLC in the phase II study. Methods: This open-label, multicenter, randomized phase II study enrolled advanced NSCLC pts who had progressed after first-line platinum-based chemotherapy, without sensitizing EGFR/ALK/ROS1 alterations, and with ECOG PS 0-1. Eligible pts were randomized 2:1 to receive anlotinib (10mg, p.o, QD, d1 to 14 of a 21-day cycle) plus docetaxel (60mg/m2, q3w, 4-6 cycles) (A+D arm) or docetaxel (60mg/m2, q3w, 4-6 cycles) alone (D arm) until disease progression or unacceptable toxicity. The primary endpoint was PFS. Secondary endpoints included the objective response rate (ORR), the disease control rate (DCR), OS and safety. Results: From Jun. 2019 to Dec. 2020, 36 pts were enrolled, 24 pts (median age: 63.0, squamous cell carcinoma: 50.0%, ECOG PS 1: 87.5%) in the A+D arm and 12 pts (median age: 60.0, squamous cell carcinoma: 50.0%, ECOG PS 1: 83.3%) in the D arm. As of Jan. 20, 2021, the median PFS were 6.2 months (95% Cl: 0.00-12.82) in the A+D arm vs 1.4 months (95% Cl: 0.71-2.09) in the D arm (HR: 0.30; 95% Cl: 0.11-0.78, p = 0.007), which remain immature because of the shorter follow-up time. The median OS was not reached. For tumor response, 32 pts were evaluable. The ORR was 27.3% in the A+D arm vs 0% in the D arm (p = 0.142), and the A+D arm showed a significantly higher DCR than the D arm (100.0% vs 50.0%, p = 0.001). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 33.3% (A+D arm) and 0.0% (D arm). The most commonly reported grade 3/4 TRAEs in the A+D arm included neutropenia (8.3%, 2/24), leukopenia (8.3%, 2/24), oral mucositis (8.3%, 2/24) and hypertension (8.3%, 2/24). No grade 5 TRAEs or deaths were observed. Conclusions: Anlotinib plus docetaxel continues to show the better clinical benefit as second-line treatment for driver-negative advanced NSCLC. The safety profile was manageable and consistent with previously reported studies. The longer follow-up time is required. Clinical trial information: NCT03726736.