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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2012 - Randomized phase 2 study comparing cisplatin + pemetrexed + bevacizumab with carboplatin + paclitaxel + bevacizumab in treatment-naïve advanced non-squamous non-small-cell lung cancer (CLEAR study)


20 Oct 2018


Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research


Ryo Koyama


Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292


R. Koyama1, H. Udagawa2, E. Sugiyama3, K. Komuta4, M. Mori5, T. Yokoyama6, T. Sasaki7, H. Saito8, H. Ishida9, H. Nakagawa10, A. Sekine11, A. Tamura12, M. Shingyoji13, K. Mizuno14, A. Nakamura15, A. Kinoshita16, T. Yamanaka17, K. Goto2

Author affiliations

  • 1 Department Of Respiratory Medicine, Juntendo University Faculty of Medicine, 1138421 - Tokyo/JP
  • 2 Department Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 3 Division Of Cancer Immunology, National Cancer Center, 277-8577 - Kashiwa/JP
  • 4 Department Of Respiratory Medicine, Osaka Police Hospital, Osaka/JP
  • 5 Department Of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka/JP
  • 6 Department Of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki/JP
  • 7 Respiratory Center, Asahikawa Medical University, Asahikawa/JP
  • 8 Department Of Thoracic Oncology, Kanagawa Cancer Center, Yokohama/JP
  • 9 Division Of Medical Oncology, Showa University School of Medicine, Tokyo/JP
  • 10 Department Of Respiratory Medicine, National Hospital Organization Hirosaki Hospital, Hirosaki/JP
  • 11 Department Of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama/JP
  • 12 Center For Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Tokyo/JP
  • 13 Division Of Respirology, Chiba Cancer Center, Chiba/JP
  • 14 Department Of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima/JP
  • 15 Department Of Pulmonary Medicine, Sendai Kousei Hospital, 980-0873 - Sendai/JP
  • 16 Department Of Respiratory Medicine, Nagasaki Prefecture Shimabara Hospital, Shimabara/JP
  • 17 Department Of Biostatistics, Yokohama City University Hospital, 236-004 - Yokohama/JP

Abstract 2012


Bevacizumab (Bev) combined with platinum-based chemotherapy is a standard treatment for advanced non-squamous non-small-cell lung cancer (non-Sq NSCLC). Cisplatin + pemetrexed (CisPem) is suggested as the most promising chemotherapy regimen combined with Bev. However, no study has been conducted to evaluate the efficacy and safety of CisPemBev compared with carboplatin + paclitaxel + bevacizumab (CarPacBev) for advanced non-Sq NSCLC.


Treatment-naïve patients with advanced or recurrent EGFR/ALK-negative non-Sq NSCLC from 55 sites across Japan were randomly assigned in a 2:1 ratio to either CisPemBev (4 cycles of Cis [75 mg/m2] + Pem [500 mg/m2] + Bev [15 mg/kg] q3wk, followed by maintenance Pem + Bev q3wk until progression) or CarPacBev (4 cycles of Car [AUC 6] + Pac [200 mg/m2] + Bev q3wk, followed by maintenance Bev q3wk until progression). The primary endpoint was progression-free survival (PFS) by central review. The secondary endpoints were overall survival (OS), overall response rate (ORR) and safety profile. The target numbers of patients and events were determined to be 210 and 170, respectively, to observe a point estimate of HR for PFS (CisPemBev/CarPacBev) <0.83 with a high probability (80%) when the true HR was 0.72. The data were cutoff in July, 2017. OS data were updated for this presentation in April, 2018.


Between May 2014 and May 2016, 199 patients were randomly assigned to receive CisPemBev (N = 132) or CarPacBev (N = 67). In the primary analysis, PFS events occurred in 171 patients. The HR for PFS by central review (CisPemBev/CarPacBev) was 0.825 (95% CI 0.600-1.134, median PFS, 7.6 vs 7.0 months), and the ORR was 57% for CisPemBev and 55% for CarPacBev. OS events occurred in 119 patients. The median survival follow-up duration was 28.3 months. The median OS was 23.4 months for CisPemBev and 21.6 months for CarPacBev (HR 0.845, 95% CI 0.583-1.242).


PFS was prolonged with CisPemBev compared with CarPacBev. However, there was no difference in OS between two arms. CisPem is the most effective chemotherapy regimen combined with Bev for advanced non-Sq NSCLC.

Clinical trial identification

Legal entity responsible for the study

National Cancer Center Hospital East.


Chugai Pharmaceutical.

Editorial Acknowledgement


H. Udagawa: Honoraria: Chugai Pharmaceutical. M. Mori: Honorarium for speech: AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, MSD, Ono Pharmaceutical, Shionogi; Research fund: Chugai. T. Yokoyama: Personal fees: Chugai Pharmaceutical, Eli Lilly Japan, outside the submitted work. T. Sasaki: Research grant: Boehringer Ingelheim and Pfizer. A. Sekine: Lecture fees: Boehringer Ingelheim, Chugai Pharmaceutical, AstraZeneca; Institutional financial support for contracted research: Boehringer Ingelheim. K. Goto: Honoraria: Chugai, Lilly Japan; Reserch grants: Chugai and Lilly Japan. All other authors have declared no conflicts of interest.

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