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Atsuto Mouri



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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.02 - A Phase II Study of Osimertinib versus Combination of Osimertinib and Chemotherapy for EGFR and T790M-Mutation Positive NSCLC (ID 3655)

      00:00 - 00:00  |  Presenting Author(s): Atsuto Mouri

      • Abstract
      • Slides

      Introduction

      Osimertinib is now available not only as a second line treatment for the patients with EGFR and T790M-mutation positive non-small cell lung cancer (NSCLC) after initial tyrosine kinase inhibitors (TKIs) but as a first line treatment for those who are TKI-naive. However, the efficacy as well as safety of osimertinib plus palatinum-based chemotherapy has not yet been evaluated.

      Methods

      We conducted a randomized phase 2 study to compare between osimertinib monotherapy and osimertinib + carboplatin + pemetrexed (hereafter, combination) in EGFR-mutation positive NSCLC patients with disease progression during first-line EGFR-TKI therapy. We enrolled adult patients with clinical stage IIIB or IV, or postoperative recurrent NSCLC harbouring susceptible EGFR and T790M mutations after preceded EGFR-TKI failure. Patients were randomly assigned to receive either an osimertinib [80 mg/day 1-21; q3w] or a combination of osimertinib [80 mg/day 1-21] with carboplatin/pemetrexed [area under the curve (AUC) = 5 and 500 mg/m2 day 1; q3w]. The primary endpoint was progression-free survival (PFS). Secondary endpoints included incidence of adverse events, response rate and overall survival. As indication of osimertinib was expanded to a first line during this study, we amended the protocol to discontinue the enrollment and perform final analyses.

      Results

      From October 2016 to January 2019, 62 patients were enrolled [31 patients osimertinib; 31 patients combination] (median age 68 (range 37-80); 53.2% male; 83.3% stage IV; 100% adenocarcinoma; 59.7% exon 19 deletion and 40.3% L858R; 45.2% never smoker). Median PFS was 15.8 months for the osimertinib arm and 14.6 months for the combination arm [hazard ratio (HR) 1.09 (95%CI: 0.51-2.32), P=0.83]. Median survival times have not been reached in both arms [hazard ratio (HR) 2.42 (95%CI: 0.82-7.15), P=0.10]. Response rate was 71.4% in the osimertinib and 53.6% in the combination arm. The rate of grade (G) ≥ 3 treatment-related adverse events was 45.2% in the osimertinib arm and 83.9% in the combination arm. Neutropenia, anemia and thrombocytopenia were more common in the combination arm and the rates of G ≥ 3 were 9.7%, 0% and 6.4% in the osimertinib arm and 51.6%, 25.8% and 29.0% in the combination arm, respectively. One episode (3.2%) of G ≥ 3 febrile neutropenia in the combination arm and two episodes (6.5%) of G ≥ 3 pneumonitis in the osimertinib arm were observed, however, these were well managed. Any unknown adverse event was not observed in the combination arm, while, more cases of dose reduction or treatment discontinuation were found in the combination arm mainly due to sustained hematological toxicities and intolerable adverse events related with skin-mucosal lesions. Median exposure to osimertinib in the combination arm was thereby shorter (350 days (range 7-938)) than those in the osimertinib arm (442 days (range 35-1050)).

      Conclusion

      This is the first randomized study to investigate the efficacy as well as safety of combination of osimertinib and chemotherapy in NSCLC patients with EGFR sensitizing mutation. Our study did not meet primary endpoint and this could be explained by reduced exposure of osimertinib in patients of the combination arm.

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.79 - Osimertinib in Poor PS Patients with T790M-Positive Advanced NSCLC after Progression of EGFR TKI Treatments (NEJ032B) (ID 3492)

      00:00 - 00:00  |  Author(s): Atsuto Mouri

      • Abstract
      • Slides

      Introduction

      Osimertinib has already been reported to be highly effective in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) -resistant patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC). However, its effectiveness and safety in those patients with poor performance status (PS) are unknown.

      Methods

      After progression by a treatment of gefitinib, elrotinib and/or afatinib patients who had T790M mutation, a Stage IIIB, IV or recurrence disease, and PS 2-4 were enrolled in this study. Osimertinib at a dose of 80 mg/day was orally administered. The primary endpoint of this phase II study was response rate (RR), and the secondary endpoints were progression free survival (PFS), overall survival (OS) and safety.

      Results

      Thirty-three patients were enrolled from February 2017 to May 2019. All patients met the eligibility criteria. Their median age was 72 years (range: 47–89). Women accounted for 81.8% of the patients, and 69.7% and 24.2% of the patients had a PS of 2 and 3, respectively. For 32 patients except for a patient with a protocol violation, the RR was 53.1% (95% confidence interval: 34.7-70.9%), and the disease control rate was 75.0%. The PFS was 4.8 months, and the OS was 11.1 months. Interstitial lung disease (ILD) at all grades and grade 3-5 were observed in 15.1% (5/33) and 6.1% (2/33), respectively, and treatment-related death by ILD occurred in one patient.

      Conclusion

      As the primary endpoint, we verified that osimertinib was sufficiently effective in EGFR TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. However, physicians should pay attention to relatively short PFS and adverse events such as ILD.

      Clinical trial information: jRCTs061180018.

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