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Akihiro Bessho



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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: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-34 - Docetaxel Plus Ramucirumab with Prophylactic PEG-G-CSF Support for Chemo-NaïVe Elderly NSCLC Patients: A Phase II Study (WJOG9416L) (ID 12400)

      16:45 - 18:00  |  Author(s): Akihiro Bessho

      • Abstract

      Background

      Docetaxel monotherapy is the standard of care for chemo-naïve Japanese elderly patients with advanced non-small cell lung cancer (NSCLC), according to our results of phase III trial comparing docetaxel and vinorelbine monotherapies (WJTOG9904). In a pivotal phase III study (REVEL), docetaxel plus ramucirumab demonstrated superior response rate (RR) and progression-free survival (PFS) over docetaxel monotherapy in second-line setting for advanced NSCLC. These differences in RR and PFS were translated into overall survival (OS) benefit. This evidence prompted us to investigate docetaxel plus ramucirumab for chemo-naïve elderly patients. However, in a similarly designed Japanese randomized phase II trial (JVCG trial), febrile neutropenia (FN) was observed in 34.2% of docetaxel plus ramucirumab arm. This high incidence of FN is a clinical concern when using docetaxel plus ramucirumab for elderly patients. The ASCO practice guideline recommends primary prophylactic granulocyte-colony stimulating factor (G-CSF) when the risk of FN is 20% or higher. PEGylated-G-CSF (pegfilgrastim) administered once a cycle demonstrated reduction of FN incidence in many types of cancers. Based on the above background, we considered that primary prophylactic PEG-G-CSF would be beneficial for elderly NSCLC patients who received docetaxel plus ramucirumab.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a prospective multicenter, single-arm, phase II study conducted by West Japan Oncology Group (WJOG). Main inclusion criteria includes: chemo-naïve; aged ≥75; histologically or cytologically confirmed NSCLC; ECOG PS 0/1; adequate organ functions; with measurable disease; without contraindication of ramucirumab; written informed consent; and estimated life expectancy of at least 3 months. Intravenous docetaxel (60 mg/m2, day 1) plus ramucirumab (10 mg/kg, day 1) with subcutaneous PEG-G-CSF (3.6 mg, day 2) every 3 weeks is administered until progression. Continuous docetaxel or ramucirumab monotherapy is permitted when intolerable toxicities occur but clinical benefit is obtained by each drug. The primary endpoint is objective response rate (ORR). Secondary endpoints are PFS, OS, disease control rate, and safety. We assumed that the threshold and expected ORR were 20% and 35%, respectively. Based on this, the number of patients was calculated to be 59 to provide a power of 80% with probability of one-sided type I error being 0.05. Taking ineligible patients into account, the sample size was set at 65. When the study results are promising, we plan to conduct a phase III trial to compare docetaxel plus ramucirumab with PEG-G-CSF support vs. docetaxel monotherapy for chemo-naïve elderly NSCLC patients. Clinical trial information: UMIN000030598.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion


      Section not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.01-40 - Randomized Phase II Study of Docetaxel Plus Bevacizumab or Pemetrexed Plus Bevacizumab for Elderly pts with Untreated Advanced NSCLC: TORG1323 (ID 12868)

      16:45 - 18:00  |  Author(s): Akihiro Bessho

      • Abstract
      • Slides

      Background

      The addition of bevacizumab (B) to platinum doublets prolongs the survival for non-squamous NSCLC. The role of monotherapy with B is unclear for elderly non-squamous NSCLC pts.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Pts were pathologically diagnosed untreated elderly (≥75 years old) non-squamous NSCLC, who were stage IIIB, IV, or recurrent disease, and PS 0-1. EGFR mutation or ALK rearranged pts were allowed after receiving each tyrosine kinase inhibitor. Pts were randomized 1:1 to receiving either docetaxel (D) or pemetrexed (P) with B. The primary endpoint was progression-free survival (PFS) assessed by independent review committee. B was administered 15 mg/kg, D was 50 mg/m2, or P was 500 mg/m2 every 3 weeks until disease progression or unacceptable toxicity based on our previous studies. Selection design was adopted for this study. The planned sample size was 120 pts to yield 80% power to select an optimal regimen correctly and PB is chosen for the further evaluation if the point estimate of hazard ratio (HR) for PFS was ≤1.20.

      4c3880bb027f159e801041b1021e88e8 Result

      Enrollment was terminated in early at the end of March 2017 because of slow accrual. Total 103 pts (DB/PB= 51/52 pts) were enrolled and 99 pts (49/50 pts) were full analysis set. Patient characteristics were well balanced between two arms. Median age was 78 (range: 75-88) in DB and 79 (75-94) in PB. EGFR mutation+/ALK translocation+/wild type/unknown= 13/0/34/2 in DB and 13/2/33/2 in PB. Total 77 events occurred at data cut-off, which corresponded to 77.7% power. The median PFS of DB and PB were 6.1 months and 4.6 months (HR 1.03, 95%C.I. 0.66-1.61: p=0.901). The response rates were 43% and 40% (p=0.840), respectively. The incident of ≥Grade 3 leukopenia (69% vs. 27%, p<0.001), neutropenia (86% vs. 44%, p<0.001) and fatigue (10% vs. 0%, p=0.027) were higher in DB. However, the frequency of febrile neutropenia was not different (16% vs.12%, p=0.578). One patient in PB was died of rupture of abdominal aortic aneurysm.

      8eea62084ca7e541d918e823422bd82e Conclusion

      PB is less toxic and the efficacy is comparable between two arms for elderly (≥75 years old) advanced non-squamous NSCLC. PB is a candidate for the further evaluation. Clinical Trial information: UMIN000012786.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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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
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      P3.01-37 - Phase II Study of Amrubicin Plus Erlotinib in Previously Treated, Advanced Non-Small Cell Lung Cancer Patients with Wild-Type EGFR: TORG 1320 (ID 12559)

      12:00 - 13:30  |  Author(s): Akihiro Bessho

      • Abstract
      • Slides

      Background

      The combination of amrubicin (AMR) and erlotinib (ERL) was reported to have synergistic effect on non-small cell lung cancer (NSCLC) cell line with wild-type EGFR in vitro. We accomplished a phase I study of AMR plus ERL in previously treated advanced NSCLC patients, and determined the maximum tolerated dose (MTD). Furthermore, we observed a high response rate of 33% (Am J Clin Oncol 2015).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a multi-center, single-arm phase II trial to evaluate the efficacy of AMR and ERL combination therapy in patients with previously treated, advanced NSCLC with wild-type EGFR. Patients were treated at 3weeks intervals with AMR (35mg/m2 on days 1-3) plus ERL (100mg/day on days 1-21). The patients without disease progression after 4 cycles continued ERL until disease progression or unacceptable toxicity. The primary endpoint is progression free survival (PFS). Secondary endpoints are response rate (RR), disease control rate (DCR), time to treatment failure (TTF), overall survival (OS), and toxicity. The concentration of trough ERL was measured after first cycle of treatment and in maintenance phase as an exploratory research to analyze relation between effectivity/safety and pharmacokinetics.

      4c3880bb027f159e801041b1021e88e8 Result

      From June 2013 to July 2016, 25 patients were enrolled. With a median follow-up of 14.3 months (95%CI: 10.9 – 17.6), median PFS was 3.6 months (95%CI: 2.1 - 5.1). The RR and the DCR were 24.0% and 64.0%, respectively. Median OS was 15.4 months (95%CI: 13.4 – 17.4). We observed grade 3 or 4 toxicities such as leukopenia (68%), neutropenia (72%), anemia (8%), febrile neutropenia (12%), anorexia (12%), oral mucositis (12%) and rash (8%). We had no treatment related death. In pharmacokinetic analysis, the mean (±SD) trough concentrations (C trough) of ERL in induction and maintenance phase were 1.070±0.463µg/mL and 0.879±0.427µg/mL, respectively. The C trough of ERL in induction phase was higher than that in maintenance phase (p=0.0371). There was no relation between C trough of ERL and any toxicity/response.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although the primary endpoint was not met in this trial, the PFS of AMR and ERL combination therapy was superior to that of AMR monotherapy which was previously reported. In this study, pharmacokinetic analysis showed that C trough of ERL were elevated in combination therapy. This combination therapy might be an optional treatment as cytotoxic chemotherapy for NSCLC patients after platinum-doublet failure. Clinical trial information: UMIN 000010582.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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