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Proffered Paper - NSCLC metastatic 1

LBA50 - ACTIVE: Apatinib plus gefitinib versus placebo plus gefitinib as first-line treatment for advanced epidermal growth factor receptor-mutant (EGFRm) non-small-cell lung cancer (NSCLC): A multicentered, randomized, double-blind, placebo-controlled phase III trial (CTONG1706)

Date

20 Sep 2020

Session

Proffered Paper - NSCLC metastatic 1

Presenters

Li Zhang

Citation

Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325

Authors

L. Zhang1, H. Zhao2, Z. Zhang3, W. Yao4, X. Min5, K. Gu6, G. Yu7, C. Cheng8, J. Cui9, L. Miao10, X. Song11, L. Zhang12, X. Yuan13, Y. Fang14, X. Fu15, C. Hu16, X. Zhu17, Y. Fan18, Q. Yu19

Author affiliations

  • 1 Department Of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510030 - Guangzhou/CN
  • 2 Department Of Clinical Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060 - Guangzhou/CN
  • 3 Department Of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060 - Guangzhou/CN
  • 4 Department Of Thoracic Oncology, Sichuan Cancer Hospital, 610042 - Chengdu/CN
  • 5 Department Of Tumor Radiotherapy, Anhui Chest Hospital, 230022 - Hefei/CN
  • 6 Department Of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, 230022 - Hefei/CN
  • 7 Department Of Medical Oncology, Weifang People's Hospital, 261000 - Weifang/CN
  • 8 Department Of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, 510080 - Guangzhou/CN
  • 9 Oncology Department Of Oncology Center, First Hospital of Jilin University, 130021 - Changchun/CN
  • 10 Department Of Respiratory, The Affiliated Hospital of Nanjing University Medical School, 210046 - Nanjing/CN
  • 11 Department Of Respiratory, Shanxi Tumor Hospital, 030000 - Taiyuan/CN
  • 12 Peking Union Medical College Hospital Of Chinese Academy Of Medical Sciences, Peking Union Medical College Hospital of Chinese Academy of Medical Sciences, 100010 - Beijing/CN
  • 13 Department Of Medical Oncology, Huizhou Municipal Central Hospital, 516001 - Huizhou/CN
  • 14 Department Of Medical Oncology, Sir Run Run Shaw Hospital,Zhejiang University School of Medicine, 310016 - Hangzhou/CN
  • 15 Department Of Respiratory And Critical Care Medicine, The Affiliated Hospital of Inner Mongolia Medical University, 010050 - Hohhot/CN
  • 16 Department Of Respiratory Medicine, Xiangya Hospital Central South University, 410008 - Changsha/CN
  • 17 Department Of Respiratory, Zhongda Hospital Southeast University, 210009 - Nanjing/CN
  • 18 Department Of Thoracic Medical Oncology, Zhejiang Cancer Hospital, 310022 - Hangzhou/CN
  • 19 Department Of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, 530021 - Nanjing/CN
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Resources

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Abstract LBA50

Background

Blocking vascular endothelial growth factor receptor (VEGFR) pathway can enhance the efficacy of EGFR-TKI in EGFRm NSCLC. ACTIVE is the first phase III study evaluating apatinib, an oral small molecule VEGFR2-TKI, or placebo plus gefitinib as first-line therapy in patients (pts) with EGFRm NSCLC.

Methods

Treatment-naïve pts with classic EGFR mutation (ex19del or L858R) were randomized (1:1) to receive once-daily oral apatinib 500 mg plus gefitinib 250 mg (AG arm) or placebo plus gefitinib 250 mg (G arm). Stratification factors: EGFR mutation type (ex19del, L858R), sex, and performance status (0, 1). The primary endpoint was PFS (RECIST 1.1) assessed by blinded independent radiology review committee (IRRC). Secondary endpoints: PFS by investigator (INV), OS, ORR, DCR, DOR, TTPD, QoL and safety. Next-generation sequencing (NGS) was used to analyze baseline and post-progression samples for exploring efficacy predictors and acquired resistance.

Results

313 pts were enrolled (AG arm, n=157; G arm, n=156). Median follow-up was 15.8 months (IQR 12.6, 20.4). Median PFS by IRCC was 13.7 versus 10.2 months in AG and G arms (HR = 0.71, 95% CI 0.54-0.95; p = 0.0189). Prolonged PFS by INV (HR = 0.71, 95% CI 0.53-0.95) was observed. OS data are immature at cutoff (29.4% events). ORR was 77.1% and 73.7% in AG and G arms (p = 0.5572). Pts with ex19del had better HR than L858R (HR = 0.67, 0.45-0.99; 0.72, 0.48-1.09). NGS results of baseline samples showed a marginally significant improved PFS in TP53-mutant disease. Pts with TP53 exon 8 mutation significantly benefited from dual blockade (HR = 0.24, 0.06-0.91). Grade 3-4 adverse events (AEs) of the two arms were similar, except increased risk of hypertension and proteinuria (46.5%; 17.8%) in AG arm. No AEs beyond expectation were reported. Other endpoints and NGS results for resistance will be presented onsite.

Conclusions

Apatinib plus gefitinib as first-line therapy demonstrated superior PFS. TP53 exon 8 mutation status could serve as an efficacy predictor. Safety profiles were consistent with that of the individual drugs and acceptable.

Clinical trial identification

NCT02824458.

Editorial acknowledgement

Legal entity responsible for the study

Sun Yat-sen University Cancer Center.

Funding

The 5010 Clinical Research Foundation of Sun Yat-sen University; Jiangsu Hengrui Medicine Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

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