Virtual Library

Start Your Search

Sanjay Awasthi



Author of

  • +

    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
    • +

      P3.01-100 - Risk of Gastrointestinal and Hepatic Toxicities in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Osimertinib (ID 11755)

      12:00 - 13:30  |  Author(s): Sanjay Awasthi

      • Abstract
      • Slides

      Background

      Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line therapy in patients with advanced non-small-cell lung cancer (NSCLC) who harbors EGFR mutation. The presence of T790M point mutation, later, mediates the resistance to first-generation and second-generation EGFR-TKIs. Osimertinib, an oral third-generation EGFR-TKI, targets both EGFR-TKI sensitizing and EGFR T790M resistance mutations. We undertook a systematic review and combined analysis of two phase III randomized controlled trials (RCT) to determine the risk of gastrointestinal and hepatic toxicities among patients with advanced NSCLC treated with osimertinib.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through March 2018. Phase III RCTs that mention diarrhea, nausea, vomiting, stomatitis and elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Fixed effects model was applied.

      4c3880bb027f159e801041b1021e88e8 Result

      Two phase III RCTs with a total of 971 patients with advanced NSCLC were included in the analysis. Studies compared osimertinib vs carboplatin/cisplatin + pemetrexed and osimertinib vs gefitinib/erlotinib. The randomization ratio was 1:1 in the FLAURA study and 2:1 in the AURA3 study. Osimertinib was utilized in T790M-positive advanced NSCLC after prior first-line EGFR-TKIs in the AURA3 study (n= 556) and as first-line treatment in the FLAURA study (n= 415). The RR of all-grade side effects were as follows: diarrhea, 1.305 (95% CI: 1.128 – 1.509, p < 0.0001); nausea, 0.480 (95% CI: 0.378–0.611; p < 0.0001); vomiting, 0.783 (95% CI: 0.561–1.092; p = 0.149); stomatitis, 1.262 (95% CI: 0.980 – 1.626, p = 0.071); elevated AST, 0.397 (95% CI: 0.277–0.569; p < 0.0001); and elevated ALT, 0.312 (95% CI: 0.212–0.458; p < 0.0001). The RR of high-grade side effects were as follows: diarrhea, 0.912 (95% CI: 0.354 – 2.347, p = 0.849); vomiting, 0.135 (95% CI: 0.022 – 0.831; p = 0.031); stomatitis, 0.532 (95% CI: 0.124 – 2.293, p = 0.397); elevated AST, 0.296 (95% CI: 0.096 – 0.907; p = 0.033); and elevated ALT, 0.112 (95% CI: 0.034 – 0.372; p < 0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients on osimertinib noted a significant increase in the risk of all-grade diarrhea. Nevertheless, the risk of developing any-grade nausea, all grades of elevated AST/ALT and high-grade vomiting, was significantly reduced in osimertinib arm, favoring osimertinib.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.01-93 - Osimertinib-Related Hematological and Pulmonary Toxicities in Advanced NSCLC Patients: Combined Analysis of Phase III Trials (ID 12137)

      12:00 - 13:30  |  Author(s): Sanjay Awasthi

      • Abstract
      • Slides

      Background

      In both epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) sensitizing and EGFR T790M resistance mutations in patients with advanced non-small-cell lung cancer (NSCLC), osimertinib, a third-generation and irreversible oral EGFR-TKI, has been shown to improve survival in studies. We performed a systematic review and meta-analysis of phase III randomized controlled trials (RCT) to determine the risk of hematological and pulmonary toxicities among patients with advanced NSCLC treated with osimertinib.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We undertook a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through March 2018. Phase III RCTs that mention hematological and pulmonary toxicities as adverse effects were incorporated in the analysis. The primary meta- analytic approach was a fixed effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI).

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 971 patients with advanced NSCLC from two phase III studies were eligible for analysis. The study arm used osimertinib while the control arm utilized either chemotherapy (carboplatin/cisplatin+ pemetrexed) or standard EGFR-TKIs (gefitinib or erlotinib). The randomization ratio was 1:1 in the FLAURA study and 2:1 in the AURA3 study. Osimertinib was utilized in T790M-positive advanced NSCLC after prior first-line EGFR-TKIs in the AURA3 study (n= 556) and as first-line treatment in the FLAURA study (n= 415). The RR of all-grade side effects were as follows: anemia, 0.594 (95% CI: 0.433 – 0.814, p = 0.001); cough, 1.122 (95% CI: 0.829 – 1.520, p = 0.455); dyspnea, 1.143 (95% CI: 0.784 – 1.666; p = 0.487); and ILD, 2.378 (95% CI: 0.984 – 5.744; p = 0.054). The RR of high-grade adverse effects were as follows: anemia, 0.175 (95% CI: 0.072 – 0.425, p < 0.001); neutropenia, 0.293 (95% CI: 0.138 – 0.623; p = 0.001); thrombocytopenia, 0.183 (95% CI: 0.060 – 0.564, p = 0.003); pneumonia, 1.237 (95% CI: 0.442 – 3.459; p = 0.685); dyspnea, 0.895 (95% CI: 1.192 – 4.175; p = 0.888); and ILD, 1.238 (95% CI: 0.404 – 3.789; p = 0.708).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our meta-analysis demonstrated that patients on osimertinib experienced a significant decrease in the risk of hematological toxicities, compared to control arm. Moreover, no increase in the risk of pulmonary toxicities was noted in the osimertinib group.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.