title: Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study.
abstract: The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  
  Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle.
  
  
  
  As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively.
  
  
  
  Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC.
  
  
  
  Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071.
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo skanda@ncc.go.jp.
authors.forename: S
authors.initials: S
authors.lastname: Kanda
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Shiraishi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: E
authors.initials: E
authors.lastname: Kubo
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Utsumi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Sunami
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: S
authors.initials: S
authors.lastname: Kitazono
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Mizugaki
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Horinouchi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: ONO Pharmaceutical Co. Ltd, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hozumi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D000077594:Nivolumab; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D000077143:Docetaxel; D000068258:Bevacizumab; D000077594:Nivolumab; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine
keywords: chemotherapy; combination; nivolumab; non-small-cell lung cancer