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H. Saka



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    OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients with Previously Treated, PD-L1-Expressing NSCLC Who Completed Pembrolizumab  (ID 6769)

      11:00 - 12:30  |  Author(s): H. Saka

      • Abstract
      • Presentation
      • Slides

      Background:
      Checkpoint inhibitors such as the anti–PD-1 monoclonal antibody pembrolizumab have demonstrated antitumor activity and a manageable safety profile in several advanced malignancies. Although checkpoint inhibitors are rapidly becoming a standard-of-care therapy in multiple tumor types, the optimal treatment duration has not been established. We assessed outcomes in patients who completed the maximum 24 months of pembrolizumab in the phase 3 KEYNOTE-010 study (NCT01905657), in which pembrolizumab provided superior OS over docetaxel in patients with previously treated, PD-L1–expressing advanced NSCLC.

      Methods:
      1034 patients with advanced NSCLC that progressed after ≥2 cycles of platinum-based chemotherapy (and an appropriate therapy for targetable EGFR and ALK aberrations if present) and had a PD-L1 tumor proportion score ≥1% were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg Q3W or to docetaxel 75 mg/m[2] until disease progression, intolerable toxicity, or physician or patient decision; the maximum duration of pembrolizumab was 24 months of uninterrupted treatment or 35 cycles, whichever was later. Response was assessed per RECIST v1.1 by independent central review every 9 weeks. After completion of 24 months/35 cycles, patients continued to undergo imaging every 9 weeks; patients with subsequent disease progression were eligible for a second treatment course if they did not receive other anticancer therapy after stopping pembrolizumab.

      Results:
      In the overall population, median OS was longer (10.5 months for pembrolizumab Q2W, 13.4 months for pembrolizumab Q3W, and 8.6 months for docetaxel) and 24-month OS rates were higher (30.1%, 37.5%, and 14.5%, respectively) with pembrolizumab compared with docetaxel. Of the 691 patients allocated to pembrolizumab, 47 patients received 35 cycles of pembrolizumab and were included in this analysis. As of the September 30, 2016 data cutoff date, all patients had completed all 35 cycles of treatment, but one withdrew from the study treatment after completing 35 cycles. Best overall response (ORR) among these 47 patients was complete response (CR) in 3 (6%) patients and partial response (PR) in 39 (83%) patients, for an ORR of 89%; 5 (11%) patients experienced stable disease (SD). Two of these patients experienced disease progression since stopping pembrolizumab and two of these patients resumed pembrolizumab therapy. As of the cutoff date, none of the 47 patients had died.

      Conclusion:
      With long-term follow-up, the OS benefit has been maintained and pembrolizumab continues to demonstrate superiority over docetaxel. Pembrolizumab provides durable clinical benefit with few patients progressing after completing two years of therapy.

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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.02-028 - A Phase I/II Study of Carboplatin, Pemetrexed, and Concurrent Radiation Therapy for Patients with Locally Advanced NSCLC. CJLSG0912 (ID 4175)

      14:30 - 15:45  |  Author(s): H. Saka

      • Abstract
      • Slides

      Background:
      A combined concurrent therapy with a platinum-based regimen and radiation is recognized as a standard for patients with unresectable stage Ⅲ lung cancer. Though combined therapy has improved survival, little improvement was reported after that for decades. Pemetrexed is a new generation drug which is widely recognized as a safe and effective agent for patients with stage Ⅳ lung cancer. Moreover pemetrexed is expected to have a synergistic effect with radiation in vitro study. The purpose of this study was to investigate safety and toxicity profile of a regimen of pemetrexed/carboplatin (Pem/CBDCA) plus concurrent thoracic radiotherapy (TRT) followed by consolidation therapy with Pem/CBDCA for Japanese patients with unresectable non-small cell lung cancer (NSCLC).

      Methods:
      We planned a multi-institutional open clinical phase Ⅰ/Ⅱ trial of Pem (500 mg/m[2]) /CBDCA (AUC=5) plus concurrent TRT for patients with stage ⅢA/ⅢB NSCLC. Patients were administered two cycles of Pem/CBDCA with three-weeks interval and delivered 60 Gy radiotherapy in 30 fractions concurrently. Additional two cycles of Pem/CBDCA with a three-weeks interval were administered after the safety of concurrent therapy was confirmed. Regarding a phase Ⅰ study, we confirmed a safety of this therapy every three consecutive patients. In case that three or more DLTs in first six patients occurred, a dose of CBDCA was to be decreased from AUC 5 to 4. We planned to enroll thirty patients in this study in total of phaseⅠandⅡ.

      Results:
      Six patients were included in the phase I study. Median follow-up period was 27.4 month. DLTs were observed in two out of six patients. This fulfilled preplanned criterion to conclude therapeutic dose. The most frequent non-hematologic adverse event was esophagitis (66.7%). Neutropenia was observed rather frequently (83.3%), but no patients developed febrile neutropenia. As to two cases of DLT, one patient experienced grade 2 radiation pneumonitis. The other patient presented prolonged leukocytopenia. Other four patients completed scheduled therapy. Five patients (83.3%) got PR. Two-year survival was 100%. Disease progression was observed in three patients during study period. Because of slow accrual, phase Ⅱ study was not conducted.

      Conclusion:
      Present therapy is feasible for Japanese patients with unresectable stage Ⅲ NSCLC. Trial registration: UMIN000008426

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    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
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      P2.06-015 - The NICE Salvage Study: A Phase II Trial of Weekly Nab-Paclitaxel in the Salvage Setting for Advanced Non-Small Cell Lung Cancer (ID 4566)

      14:30 - 15:45  |  Author(s): H. Saka

      • Abstract
      • Slides

      Background:
      The standard chemotherapy for advanced NSCLC after the failing of second or third line chemotherapy has yet to be established. In these salvage setting patients the acceptable safety and efficacy of solvent-based paclitaxel (sb-P) monotherapy have been previously reported as one possible treatment option (Anticancer Res 2005). Compared with sb-P, nab-paclitaxel(nab-P) yielded a higher mean maximal circulating concentration of free paclitaxel and delivered higher drug concentration to tumors in preclinical xenograft models (Clin. Cancer Res. 2006). Moreover, a large multicenter international phase III study (CA031) of nab-P + carboplatin (C) vs sb-P + C, nab-P + C produced a significantly higher overall response rate (ORR) compared with sb-P + C, and had an acceptable safety profile as a first line chemotherapy (J. Clin. Oncol. 2012) .These results suggest that nab-P monotherapy have possibility to be more efficacious and tolerable compared to sb-P monotherapy. KTOSG trial 1301 has recently revealed weekly nab-P as a second line chemotherapy is associated with acceptable toxicity and a favorable ORR in patients with advanced NSCLC (Lung Cancer 2016). However, there are no reports of nab-P monotherapy after the failing of second or third line chemotherapy. We therefore planned this study aiming to assess the efficacy and safety of nab-P monotherapy for patients in the salvage setting.

      Methods:
      This multicenter single arm phase II study assesses the efficacy of nab-P in pts with PS 0-2 and aged < 75 years with advanced non-small cell lung cancer. Pts must have failed two or three prior lines of therapy including at least a platinum- containing chemotherapy. Pts pretreated with sb-P or nab-P, or tumors harboring EGFR mutation or ALK fusion gene are excluded. Pts receive nab-P 80 mg/m2 on days 1,8 and 15 of a 28-days cycle. The primary endpoint of the trial is progression-free survival in an intent-to-treat analysis using the Kaplan-Meier method and log-rank test. Secondary endpoints include overall survival, ORR, disease control rate, efficacy according to prior docetaxel, quality of life, and safety. The study is powered to detect a 1.5-month improvement in median PFS in this investigational arm beyond the 2.0-month median PFS estimated from historical data. Assuming a one-sided 0.10 level of Type I error and 80% power, the sample size was calculated to be 35 pts based on the Brookmeyer-Crowley method. The target sample size is established as 38 pts. As of June 2016, 14 pts were registered and recruitment is ongoing (UMIN000016173).

      Results:
      Section not applicable

      Conclusion:
      Section not applicable

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