Anlotinib vs placebo as third- or further-line treatment for patients with small cell lung cancer: a randomised, double-blind, placebo-controlled Phase 2 study

Cheng, Ying; Wang, Qiming; Li, Kai; Shi, Jianhua; Liu, Ying; Wu, Lin; Han, Baohui; Chen, Gongyan; He, Jianxing; Wang, Jie; Lou, Donghua; Yu, Hui; Wang, Shan-chun; Qin, Haifeng; Li, Xiaoling

doi:10.1038/s41416-021-01356-3

Cited by 95 publications

(114 citation statements)

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“…Clinical data were mainly derived from a phase II randomized controlled trial (ALTER 1202, NCT03059797) that compared anlotinib versus placebo in patients with relapsed SCLC who had experienced failure of at least two lines of chemotherapy [6]. Patients were randomly assigned (2:1) to receive anlotinib (n = 82) or placebo (n = 38) 12 mg orally once daily for 2 weeks and then 1 week off until disease progression or development of intolerable toxicity.…”

Section: Patientsmentioning

confidence: 99%

“…Patients who survived either remained in the PFS state or transferred to the PD state, and those transferred to the PD state either remained or died [7][8][9][10]. The Markov cycle was set as 1 month with a time horizon of 5 years, considering that the probability of survival to year 5 after the SCLC diagnosis was only 6% [11] and the median OS of patients with advanced SCLC was\1 year in ALTER 1202 [6]. Transition probabilities between different health states were calculated based on the equation as follows: P (1 month) = 1 -(0.5) (1/median time to event) , derived from the equations: P = 1 -e -R and R = -ln[0.5]/(time to event/number of treatment cycles) (for clinical outcomes, see Table 1) [12,13].…”

Section: Model Structurementioning

confidence: 99%

“…The primary utility values were 0.804 and 0.321 for PFS and PD state, respectively, which were obtained from the previously published studies [15,16]. The utility decrements associated with side effects were calculated based on the occurrence of grade C 3 adverse events (AEs) in ALTER 1202 [6]. Thus, the utility of PFS state was 0.791 for the anlotinib group and 0.803 for placebo.…”

Section: Utility Estimatesmentioning

confidence: 99%

“…[17] in China, respectively [7,18]. According to ALTER1202, chemotherapy was the most common subsequent therapy after progression in both arms (82.2% vs. 83.3) [6]. Based on the Chinese Society of Clinical Oncology (CSCO) guideline for SCLC and local clinical expert opinions, the subsequent therapy after progression was assumed to be carboplatin ?…”

Section: Measurement Of Costsmentioning

confidence: 99%

“…Targeted therapy has achieved great success in lung cancer, but is mainly reflected in NSCLC. Anlotinib, a novel oral multi-target tyrosine kinase inhibitor (TKI), significantly prolonged both progression-free survival (PFS) (4.1 vs. 0.7 months, P \ 0.0001) and overall survival (OS) (7.3 vs. 4.9 months; P = 0.0210) compared with placebo for refractory SCLC as a third-or further-line treatment [6]. It is a promising treatment option for patients with relapsed SCLC who failed C 2 lines of chemotherapy and has been approved by National Medical Products Administration (NMPA) of China in 2019.…”

Section: Introductionmentioning

confidence: 99%

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Cost-Effectiveness Analysis of Anlotinib as Third- or Further-Line Treatment for Relapsed Small Cell Lung Cancer (SCLC) in China

et al. 2021

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Introduction The survival of patients with relapsed small cell lung cancer (SCLC) has achieved little progress in the last several decades. ALTER1202 confirmed the efficacy and safety of anlotinib as a third- or further-line option for relapsed SCLC. This study aimed to assess the cost-effectiveness of anlotinib compared with placebo as third- or further-line treatment for advanced SCLC in China. Methods A Markov model was developed to simulate the process of advanced SCLC and estimate the incremental cost-effectiveness ratio (ICER) of anlotinib versus placebo. The health outcomes and utilities were derived from the ALTER1202 (NCT03059797) and published sources, respectively. Total costs were calculated from the perspective of Chinese society. One-way and probabilistic sensitivity analyses (PSA) were conducted to explore the model uncertainties. Results Anlotinib was estimated to result in an additional 0.12 quality-adjusted life-years (QALYs) at an incremental cost of $2131.32, resulting in an ICER of $17,741.94/QALY. The ICER did not exceed the willingness-to-pay (WTP) threshold of $30,833 per QALY, which was three times the gross domestic product (GDP) per capita of China in 2019. One-way sensitivity analysis showed that the cost of anlotinib exerted the maximum influence on the result of the model, followed by the utility of progression-free survival (PFS) state in the anlotinib group and median overall survival (mOS) in the anlotinib group. In PSA, the probability of anlotinib being cost-effective was 26.6% and 78.5% when the WTP threshold was one and three times the GDP per capita, respectively. Conclusion Anlotinib is likely to be a cost-effective option compared with placebo for patients with relapsed SCLC who experience failure of at least two lines of chemotherapy in China. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01889-2.

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Section: Patientsmentioning

confidence: 99%

Section: Model Structurementioning

confidence: 99%

Section: Utility Estimatesmentioning

confidence: 99%

Section: Measurement Of Costsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cost-Effectiveness Analysis of Anlotinib as Third- or Further-Line Treatment for Relapsed Small Cell Lung Cancer (SCLC) in China

et al. 2021

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Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer

Cheng

Liang

et al. 2022

JAMA

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ImportanceProgrammed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.ObjectiveTo evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.Design, Setting, and ParticipantsThis international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.InterventionsPatients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.Main Outcomes and MeasuresThe primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P &lt; .012). There were 13 secondary outcomes, including progression-free survival and adverse events.ResultsAmong the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P &lt; .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.Conclusions and RelevanceAmong patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT04063163

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Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer

Cheng,

Zhang,

et al. 2024

JAMA Oncol

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ImportancePatients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.ObjectiveTo evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.Design, Setting, and ParticipantsThis multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China. Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC. Data were analyzed between May 6, 2023, and June 1, 2024.InterventionsPatients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment.Main Outcomes and MeasuresThe primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing results identified correlative biomarkers for clinical efficacy.ResultsAmong 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP. By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months. Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio [HR], 0.67 [95% CI, 0.54-0.82]; P &lt; .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; P = .03). The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group. Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, HLA-A11+ HLA-B62− haplotype, wild-type KMT2D and COL4A4, or sequence variations in CTNNA2 or SCN4A correlated with favorable PFS and OS in the toripalimab group. No new safety signals were observed. Grade 3 or higher treatment-emergent adverse event incidence was similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively).Conclusions and RelevanceIn this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC.Trial RegistrationClinicalTrials.gov Identifier: NCT04012606

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Anlotinib vs placebo as third- or further-line treatment for patients with small cell lung cancer: a randomised, double-blind, placebo-controlled Phase 2 study

Cited by 95 publications

References 24 publications

Cost-Effectiveness Analysis of Anlotinib as Third- or Further-Line Treatment for Relapsed Small Cell Lung Cancer (SCLC) in China

Cost-Effectiveness Analysis of Anlotinib as Third- or Further-Line Treatment for Relapsed Small Cell Lung Cancer (SCLC) in China

Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer

Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer

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