OA13.03 Anlotinib as Third-Line or Further-Line Treatment in Relapsed SCLC: A Multicentre, Randomized, Double-Blind Phase 2 Trial

Abstract

Background: The role of 18 fludeoxyglucose ( 18 F-FDG) PET/CT in the management of limited stage small-cell lung cancer (LS-SCLC) is uncertain. Previous studies have shown that 18 F-FDG PET/CT upstages up to 30% of LS-SCLC patients. Data from the CONVERT trial was analysed to investigate the impact of 18 F-FDG PET/CT in the management of LS-SCLC. The prognostic significance of pre-treatment 18 F-FDG PET parameters was also investigated in an exploratory analysis. Method: CONVERT is an international multi-centre phase III trial that randomly assigned fit patients to receive either twice-daily (45Gy in 30 fractions) or once-daily (66Gy in 33 fractions) radiotherapy starting on day 22 of chemotherapy cycle 1 (NCT00433563). Chemotherapy consisted of 4-6 cycles of cisplatin and etoposide. Prophylactic cranial irradiation was offered, if indicated. Contrast-enhanced thorax and abdomen CT and brain imaging (with/ without bone scintigraphy according to clinical indication) were mandated for all CONVERT participants (conventional imaging). Staging with 18 F-FDG PET/CT was allowed but not mandated. The primary endpoint was overall survival. Pre-treatment 18 F-FDG PET metabolic parameters were investigated in a subset of patients (n¼96) including standardised uptake values (max, mean and peak), volumetric and heterogeneity parameters. Result: Of 547 patients recruited to CONVERT, 540 patients with data on staging investigations and outcome were included in this analysis. The use of staging 18 F-FDG PET/CT was variable in the 8 countries recruiting to CONVERT (range, 41-100%). Compared to patients who underwent conventional imaging (n¼231), patients who were also staged with 18 F-FDG PET/CT (n¼309) had smaller gross tumour volume (p¼0$003), were less likely to have elevated pre-treatment serum lactate dehydrogenase (p¼0$035), and received more chemotherapy cycles (p¼0$026). There were no other significant differences in baseline and treatment characteristics between the two groups. There were no significant differences in overall (hazard ratio 0$87 [95% CI 0$70-1$08]; p¼0$192) and progression-free survival (hazard ratio 0$87 [95% CI 0$71-1$07]; p¼0$198) between patients staged with 18 F-FDG PET/CT in addition to conventional imaging or with conventional imaging alone. These results were observed irrespective of treatment group (once-daily and twice-daily radiotherapy). Pre-treatment 18 F-FDG PET parameters were also not prognostic. Conclusion: In CONVERT, survival outcomes were not different in LS-SCLC patients staged with or without 18 F-FDG PET/CT. This was despite those patients staged with 18 F-PET/CT having more favourable baseline and treatment characteristics. Our findings suggest that conventional imaging is sufficient to select LS-SCLC patients for concurrent chemoradiotherapy.Background: The interim analysis of our prospective trial, which compared irradiation to pre-chemotherapy or post-chemotherapy tumour extent while application of involved field radiotherapy (IFRT) for limited-stage small cell lung cancer (SCLC...

Emerging therapies for small cell lung cancer

“…The observed toxicity profile in this study was similar to a previous study of anlotinib in NSCLC. G 3–4 toxicity was slightly higher than in the placebo group with on target toxicity of bleeding in the form of hemoptysis being the most serious complication observed on the study, which occurred in four patients with only one case requiring treatment intervention [61].…”

Anlotinib as a molecular targeted therapy for tumors (Review)

“…Regarding the efficacy of anlotinib in SCLC, another multicenter, randomized, double-blind phase II trial was performed. Cheng et al (38) investigated anlotinib vs. placebo for the third-or further-line treatment of SCLC (ALTER1202, NCT03059797). In the trial, 120 enrolled patients with limited-or extensive-stage SCLC who failed at least 2 lines of chemotherapy were randomized at a 2:1 ratio to the anlotinib arm or placebo arm (12 mg per os QD from day 1 to 14, every 3 weeks).…”

“…However, it is also associated with various AEs that may affect the QoL of patients and hinder patient compliance to treatment. Studies have indicated that the percentage of AEs (all grades) that occurred in anlotinib-treated patients was 87.70-100%, and grade 3 or higher AEs were reported in 21.67-61.90% of anlotinib-treated patients (34,37,38,62,65), and the percentages differed among the clinical trials. The most common AEs associated with anlotinib treatment included hypertension, HFSR, fatigue, diarrhea and anorexia.…”

Successful treatment of a patient with small cell lung cancer receiving hemodialysis, with concurrent oral etoposide and radiotherapy

“…In view of excellent outcomes in the ALTER 1202 trial, the use of anlotinib as third-line and further-line therapy or maintenance therapy to prolong PFS was approved by the CSCO in China to treat SCLC. [15] However, results of the use of immune checkpoint inhibitors in SCLC seem disappointing. Nevertheless, research is ongoing.…”