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Yong Fang
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P86 - Targeted Therapy - Clinically Focused - New Target (ID 263)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P86.22 - Anlotinib plus Docetaxel versus Docetaxel as 2nd Line Treatment in Advanced Non-Small Cell Lung Cancer: A Phase I/II Study (ID 1101)
00:00 - 00:00 | Presenting Author(s): Yong Fang
- Abstract
Introduction
Docetaxel is a standard second-line treatment in advanced non-small cell lung cancer (NSCLC), of which the treatment effect is limited. Anlotinib significantly improved progression-free survival (PFS) and overall survival (OS) of advanced NSCLC patients (pts) in ALTER 0303 trial. We conducted a phase I/II study to find the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of anlotinib when combined with docetaxel and evaluate the efficacy and safety of anlotinib plus docetaxel versus docetaxel as second-line treatment in pts with driver gene negative advanced NSCLC.
Methods
Eligible pts were adults (18~75 years) with advanced NSCLC, progressed after platinum-based chemotherapy, without sensitizing EGFR mutation/ ALK rearrangement/ROS1 rearrangement, and with an ECOG performance status score of 0/1. In the phase I trial, pts received docetaxel (60mg/m2, q3w, 4-6 cycles) and anlotinib (8~12mg, QD, 2-week on/1-week off). Dose exploration was based on dose-limiting toxicities (DLTs) in first cycle and used a 3+3 dose de-escalation design to define the MTD/RP2D (primary endpoint). In the phase II trial (a multi-center, open-label, randomized controlled trial), enrolled pts were randomly assigned (2:1) to receive anlotinib (the MTD/RP2D, QD, 2-week on/1-week off) combined with docetaxel (60mg/m2, q3w, 4-6 cycles) as the treatment group or docetaxel (60mg/m2, q3w, 4-6 cycles) alone as the control group until disease progression or intolerable toxicity. The primary endpoint for the phase II part was PFS. Secondary endpoints included the objective response rate (ORR), the disease control rate (DCR), OS and safety. Clinical trial information: NCT03726736.
Results
Between November 2018 and May 2019, 8 pts (median age: 61.25, squamous cell carcinoma: 62.5%, ECOG PS 1:100%) were enrolled in the phase I trial, 5 pts in 12mg cohort and 3 pts in 10mg cohort. 2 of 5 pts in 12mg cohort had DLTs (a grade 3 Hypertension and a grade 3 Oral Mucositis) and none of 3 pts in 10mg cohort had DLTs. Thus, the MTD/RP2D for anlotinib when combined with docetaxel was 10mg (QD, 2-week on/1-week off). At data cut-off (August 16, 2020), we recruited 20 pts in the phase II trial, 14 pts in the treatment group and 6 pts (one withdrawing his consent after randomization) in the control group. Among the 14 pts in the treatment group, 4 pts reached partial response (PR) and 10 had stable disease (SD). In the control group, 2 pts exhibited by SD and one achieved by PD. The ORR was 28.6% in the treatment group vs. 0% in the control group. Moreover, the treatment group showed a significantly higher DCR than the control group (100.0% vs. 40.0%). The most common grade 1-2 adverse events (AEs) in the treatment group included neutropenia (21.4%, 3/14), decreased platelet count (14.3%, 2/14), hand-foot syndrome (14.3%, 2/14) and white blood cells reductions (14.3%, 2/14). No treatment-related grade 3 or higher AEs were observed.
Conclusion
Anlotinib combined with docetaxel exhibited better therapeutic efficacy than docetaxel alone as second-line treatment in platinum-based therapy treated advanced NSCLC, and the combination had a manageable safety profile. The MTD/RP2D for anlotinib was 10mg (QD, 2-week on/1-week off).
