Virtual Library

Start Your Search

M.H. Hong



Author of

  • +

    MA 12 - Circumventing EGFR Resistance (ID 665)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      MA 12.01 - A Phase Ib Study of the Combination of Afatinib and Ruxolitinib in EGFR Mutant NSCLC Progressed on EGFR-TKI: An Updated Analysis (ID 9021)

      11:00 - 11:05  |  Author(s): M.H. Hong

      • Abstract
      • Presentation
      • Slides

      Background:
      T790M mutation of EGFR exon 20 is observed in approximately 50% of the non-small cell lung cancer (NSCLC) patients progressed on EGFR tyrosine kinase inhibitors (TKIs). Based on a preclinical study demonstrating that pharmacologic JAK1 inhibition increased the anti-tumor activity of afatinib in T790M-positive NSCLC cell lines, we conducted a phase Ib study to evaluate the safety and efficacy of the combination of afatinib and ruxolitinib, a selective JAK inhibitor, in NSCLC patients who had progressed on EGFR-TKIs.

      Method:
      We used the classical 3+3 design for dose-escalation cohort (DAC). Patients with histologically diagnosed, EGFR mutant stage IV NSCLC and documented disease progression on EGFR-TKIs were considered eligible. Afatinib was administered alone once daily from day 1 through day 8 (run-in period), then ruxolitinib was orally administered twice daily concomitantly with afatinib until progression. The primary endpoint was to determine RP2D and DLT. If DLT was not observed in 9 patients at the cohort of the highest level, we planned to decide RP2D and enroll 6 additional patients in the dose-expansion cohort (DEC).

      Result:
      As of June 14, 2017, 21 patients (12 with exon19 deletion, 9 with exon21 L858R) were enrolled in DAC, 8 of which had T790M mutations. All patients were previously treated with erlotinib (n=6) or gefitinib (n=15), and previously received a median of 2 (range, 1-4) lines of chemotherapy. Because no DLT was observed in the 9 patients at the highest dose level (afatinib 50 mg once daily plus ruxolitinib 25 mg twice daily), 6 patients with T790M mutation were enrolled in the DEC. Frequent AEs included paronychia (G1 in 11 cases, G2 in 2 cases), diarrhea (G1 in 14 cases, G2 in 2 cases, and G3 in 2 cases), acneiform rash (G1 in 13 cases), and oral mucositis (G1 in 7 cases, G2 in 3 cases). SAEs were reported in 6 patients, which were not related to the investigational products. Partial responses were observed in 7 patients (25.9%) with disease control rate (CR+PR+SD) of 96.3%. Median PFS was 5.7 months (95% CI, 4.2-7.2) and 3 patients remain on study.

      Conclusion:
      The combination of afatinib with ruxolitinib was well tolerated with clinical benefit of disease control in NSCLC with acquired resistance to EGFR-TKIs (NCT02145637).

      Only 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, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      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.