Efficacy and safety analysis of anlotinib combined with etoposide plus cisplatin/carboplatin as first-line therapy for extensive-stage small cell lung cancer (SCLC): The final results from a phase II single-arm trial.

Abstract

8560 Background: In recent years, the therapeutic regimens of extensive-stage small cell lung cancer (ES-SCLC) have progressed a lot. The most significant clinical studies include IMpower133 and CASPIAN. However, the relevant results showed that the combination of PD-L1 monoclonal antibody and EC regimen chemotherapy as first-line treatment of small cell lung cancer have a median PFS (progession-free survival) of about 5 months, which is comparable to that of simple chemotherapy. Therefore, the EP/EC is still the standard treatment for extensive-stage small cell lung cancer. Meanwhile, we noticed that anlotinib (multi-target small molecule oral VEGF inhibitor) has a curative effect on patients with extensive-stage SCLC as a third-line or above treatment in the ALTER 1202 study in China. Therefore, we tried to add anlotinib to the first-line treatment with EP/EC regimen in patients with ES-SCLC to observe the efficacy and safety. Methods: Eligible ES-SCLC pts (18̃75 years old, initial treatment, no obvious heart, liver and kidney dysfunction) were received anlotinib (12mg QD from day 1 to 14 of a 21-day cycle) + etoposide(100mg/m2, d1̃3 of a 21-day cycle)+CBP (AUC = 4̃5,d1,Q3W) or DDP (70̃75mg/m2, d1,Q3W) for 4̃6 cycles, then anlotinib maintenance (12mg QD from day 1 to 14 of a 21-day cycle) until the disease progresses or intolerable adverse reactions occur. During the treatment, dose reduction of anlotinib was permitted, which could be reduced to 10mg or 8mg if it was intolerable. The main observation endpoints were ORR, PFS and adverse events. Results: Between January 2019 and August 2020, a total of 20 patients with extensive-stage SCLC were enrolled in the study, with an average age of 66.2 ± 8.1(45-75) years old, 17 males (85%) and 3 females (15%). The median PFS was 10 months (95% CI: 7.809-12.191), median OS was 15 months (95%CI:10.639-19.361), ORR (objective remission rate) was 90% and DCR (disease control rate) was 100%. The most common grade 3 or 4 adverse events related to the trial regimen included: neutropenia was 10/20 (50.0%), thrombocytopenia was 5/20 (25.0%), anemia, nausea and fatigue were all 2/20 (10%), hypertension, transaminase elevation and hoarseness were all 1/20 (5%). Conclusions: Anlotinib combined with EP/EC regimen has better PFS, OS, ORR and DCR for the initial treatment of extensive-stage SCLC, and a manageable safety profile. A randomized, controlled phase III clinical study will be conducted to confirm this conclusion. Clinical trial information: ChiCTR2000035043.

The Efficacy and Safety of Anlotinib in Extensive-Stage Small Cell Lung Cancer: A Multicenter Real-World Study

“… 11 Moreover, some small sample clinical trials found that the efficacy of anlotinib combined with chemotherapy was better than chemotherapy alone. 12 , 19 , 20 Nevertheless, the real-world efficacy and safety of anlotinib in ES-SCLC are still worthy of further exploration. Therefore, we conducted this multicenter real-world study to address this issue.…”

“…Some small sample size phase II clinical trials have shown the superiority of anlotinib combined with EP/EC chemotherapy as first-line treatment for ES-SCLC. In 2021 ASCO meeting, the result by Kong et al showed that the median PFS was 10.0 months, the median OS was 15.0 months, the ORR was 90%, and the DCR was 100% 12 of 20 ES-SCLC patients. Supported by these encouraging preliminary results, Phase III clinical trials of anlotinib combined with EP/EC chemotherapy in treatment-naive SCLC have already begun in China.…”

“…It was significantly higher than that of traditional chemotherapy. 12 At present, several clinical trials of anlotinib in the treatment of SCLC are progressed in China.…”

The efficacy and safety of anlotinib combined with platinum-etoposide chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A Chinese multicenter real-world study

“…In China, anlotinib has been approved by CFDA as the third-line and above treatment for SCLC based on the ALTER 1202 study (17). Several small sample size single arm phase II clinical trials of anlotinib (18)(19)(20). Antiangiogenic therapy can improve drug delivery efficiency by opening the vascular normalization window, thus exerting a synergistic effect when combined with other regimens (25).…”

“…Based on ALTER 1202 study, anlotinib was approved by the China Food and Drug Administration (CFDA) in 2019 as the third-line and above treatment for SCLC (17). Additionally, some small sample size clinical trials in China have shown the favorable efficacy of anlotinib combined with platinum-etoposide chemotherapy (18)(19)(20). The 2021 American society of clinical oncology (ASCO) meeting announced the preliminary result of a phase II clinical study on the efficacy and safety of anlotinib combined with platinum-etoposide chemotherapy in the first-line treatment of ES-SCLC.…”