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Shen Zhao

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-110 - Three Specific HER2 Mutations Predict Favorable Outcomes in Advanced Lung Cancer Patients Treated with Afatinib (ID 12862)

      16:45 - 18:00  |  Presenting Author(s): Shen Zhao

      • Abstract
      • Slides


      HER2 mutation is a potential therapeutic target for non-small cell lung cancer (NSCLC). However, HER2-targeting therapies including trastuzumab, afatinib and T-DM1 show limited and inconsistent efficacies in HER2-mutant NSCLC, suggesting its heterogeneity and the need to refine patient selection strategy for this population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      To investigate the efficacy of afatinib in HER2-mutant NSCLC and develop NGS (next generation sequencing)-based patient selection strategy, we reviewed afatinib-treated, HER2-mutant advanced NSCLC in 8 different institutions across China. HER2 status of all included cases were tested using NGS. Patients with EGFR/ALK co-mutations were excluded. The primary endpoint was investigator-assessed objective response rate (ORR) using RECIST v1.1. The secondary endpoint was progression-free survival (PFS). Adopting the binomial exact method (one-sided type I error=10%, power=80%, P0=20%, P1=30%), at least 21 patients were needed.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 30 January 2018, a total of 23 afatinib-treated, HER2-mutant NSCLC patients were identified. Among 16 evaluable patients, 4 patients achieved partial responses (PR; ORR=25%), 7 achieved stable diseases (SD) and 5 had disease progression (PD) within 6 weeks. Median PFS (mPFS) for patients achieving disease control (n=11; 69%) was 9.53 months (range: 1.77-11.97). Two of the four partial responders had p.G778_P780dup, one had p.Y772_A775dup and one had p.G776delinVC. Same mutations were detected in five other patients. Patients harboring the three specific HER2 mutations (p.G776delinsVC (n=3); p.Y772_A775dup (n=3); p.G778_P780dup (n=2)) had marginally higher ORR (ORR=50%, P=0.077) and longer PFS (mPFS=9.53m, P=0.057) than those carrying other types of HER2 mutations (n=8: ORR=0%, mPFS=1.80m) (Figure 1). TP53 co-mutation was observed in 6 patients, who showed similar responses to afatinib (PR=2, SD=2, PD=2) comparing to patients without co-occurring TP53 (n=10: PR=2, SD=5, PD=3).figure 1.tif

      8eea62084ca7e541d918e823422bd82e Conclusion

      HER2-mutant NSCLC represents a heterogenous group of diseases. Although afatinib failed to show the expected ORR in the overall population, patients harboring three specific HER2 mutations may still benefit from afatinib treatment.


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