Author of

• 25955

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

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27448

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    P3.01-90 - A Phase II Study Evaluating Continuation of EGFR-TKIs Beyond Progressive Disease Followed by the Addition of CDDP+PEM+Bev (ID 12846)

    12:00 - 13:30  |  Author(s): Toshiaki Kikuchi
    • Abstract

    Background
    

    Previous studies demonstrated that EGFR- tyrosine-kinase inhibitors (EGFR-TKIs) have antitumor effects even after disease progression during EGFR-TKI treatment. In this phase II study (NLCTG1301), we assessed the safety and efficacy of continuing EGFR-TKIs beyond progressive disease followed by the addition of cisplatin (CDDP), pemetrexed (PEM) and bevacizumab (Bev) in patients with EGFR mutation-positive advanced NSCLC with acquired resistance to first-line EGFR-TKIs.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Eligible patients were aged at least 20 years with histologically confirmed, cytotoxic chemotherapy-naive, stage IIIB–IV EGFR mutation-positive NSCLC with previous disease control for at least 6 months with first-line EGFR-TKIs. Patients received CDDP 75 mg/m², PEM 500 mg/m² and Bev 15 mg/kg on the first day of each cycle with the continuation of EGFR-TKIs. After completion of a maximum of four chemotherapy cycles, patients continued EGFR-TKIs along with maintenance Bev and PEM until disease progression. The primary endpoint was response rate according to RECIST version 1.1.

    4c3880bb027f159e801041b1021e88e8 Result
    

    The study was terminated because of slow accrual. Between March 2013 and January 2018, 10 patients were enrolled in this trial and were evaluable for safety and efficacy. Their subtypes of EGFR mutation were exon 19 deletions (7 cases), L858R (2 cases), and L858R+790M (1 case). EGFR-TKIs used in initial treatment were gefitinib (7 cases), erlotinib (3 cases), and the efficiency was PR (9 cases) and SD (1 cases). The objective response rate was 70%, median progression-free survival was 11.4 months, and median overall survival was not reached. The reasons for discontinuation were 6 cases with disease progression, 3 cases with toxicity (Gr3 infection, Gr3 g-GTP increased, Gr2 creatinine increased), and one case with bone fracture caused by accidental falling. Although there were 3 cases of treatment discontinuation due to toxicities, no serious adverse events were observed in the current study. After acquisition of resistance to EGFR-TKIs, tumor re-biopsy was performed in 4 cases, of which T790M was confirmed in 2 cases.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    This study showed the possibility of benefit of the addition of CDDP+PEM+Bev to EGFR-TKIs in patients with acquired resistance. However, further investigation of this strategy seems to be difficult because of the approval of osimertinib and the results of the IMPRESS study.

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