Multiplex molecular profiling in advanced non-small cell lung cancers

• Project/Area Number: 24501359
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Kyushu University (2013-2014); Kinki University (2012)
• Principal Investigator: OKAMOTO Isamu 九州大学, 大学病院, 特任准教授 (10411597)
• Co-Investigator(Kenkyū-buntansha): NAKAGAWA Kazuhiko 近畿大学, 医学部, 教授 (40298964) ; NISHIO Kazuto 近畿大学, 医学部, 教授 (10208134) ; SAKAI Kazuko 近畿大学, 医学部, 助教 (20580559)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 非小細胞肺癌 / 分子標的治療 / EGFR遺伝子変異 / EML4-ALK融合遺伝子

Outline of Final Research Achievements

The primary platform for genotyping of tumors adopted in the present study is the Sequenom MassARRAY system. Among 200 patients with advanced nonsquamous NSCLC, 18 (9.0%) were positive for EML4-ALK, 31 (15.5%) harbored EGFR mutations, and 151 (75.5%) were wild type for both abnormalities. Platinum-based combination chemotherapy showed similar efficacies in the EML4-ALK, EGFR-mutation, and wild-type cohorts in terms of response rate and progression-free survival, and overall survival.
We further tested FFPE specimens of NSCLC tissue for multiple genetic abnormalities simultaneously with the use of multiplex assay panels based on MassARRAY. Although most of the collected specimens were obtained by transbronchial biopsy and were small in size, >90% were successfully genotyped, thus satisfying the dual requirements of pathological diagnosis and multiplex analysis of somatic mutations with a single biopsy sample.

Research Products

• [Journal Article] Multiplex genomic profiling of non–small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin: results of a West Japan Oncology Group study (2014)
  • Author(s): Okamoto I, Sakai K, Morita S, Yoshioka H, Kaneda H, Takeda K, Hirashima T, Kogure Y, Kimura T, Takahashi T, Atagi S, Seto T, Sawa T, Yamamoto M, Satouchi M, Okuno M, Nagase S, Takayama K, Tomii K, Maeda T, Oizumi S, Fujii S, Akashi Y, Nishino K, Ebi N, Nakagawa K, Nakanishi Y, Nishio K.
  • Journal Title: Oncotarget Volume: 5 Pages: 2293-2304
  • Peer Reviewed / Open Access
• [Journal Article] Association of PD-L1 overexpression with activating EGFR mutations in surgically resected non-small cell lung cancer. (2014)
  • Author(s): Azuma K, Ota K, Kawahara A, Hattori S, Iwama E, Harada T, Matsumoto K, Takayama K, Takamori S, Kage M, Hoshino T, Nakanishi Y, Okamoto I
  • Journal Title: Annals of Oncology Volume: 25 Issue: 10 Pages: 1935-1940
  • DOI: 10.1093/annonc/mdu242
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Targeting MET Amplification as a New Oncogenic Driver. (2014)
  • Author(s): Kawakami H, Okamoto I, Okamoto W, Tanizaki J, Nakagawa K, Nishio K.
  • Journal Title: Cancers(Basel) Volume: 6(3) Issue: 3 Pages: 1540-52
  • DOI: 10.3390/cancers6031540
  • Peer Reviewed / Open Access
• [Journal Article] Development of ALK inhibitors and molecular diagnosis in ALK rearrangement–positive lung cancer. (2014)
  • Author(s): Iwama E, Okamoto I (Correspondence author), Harada T, Takayama K, Nakanishi Y
  • Journal Title: OncoTargets and Therapy Volume: 7 Pages: 375-385
  • Peer Reviewed
• [Journal Article] Survival outcome assessed according to tumor response and shrinkage pattern in patients with EGFR mutation-positive non-small cell lung cancer treated with gefitinib or erlotinib. (2014)
  • Author(s): Takeda K, Okamoto I (Correspondence author), Nakagawa K
  • Journal Title: Journal of Thoracic Oncology Volume: 9(2) Pages: 200-204
  • Peer Reviewed
• [Journal Article] Bilateral ovarian metastasis of non-small cell lung cancer with ALK rearrangement (2014)
  • Author(s): Fujiwara A, MD, Higashiyama M, Kanou T, Tokunaga T, Okami J, Kodama K, Nishino K, Tomita Y, Okamoto I (Correspondence author)
  • Journal Title: Lung Cancer Volume: 83(2) Pages: 302-304
  • Peer Reviewed
• [Journal Article] EML4-ALK-targeted therapy for advanced non-small cell lung cancer: molecular and clinical aspects. (2012)
  • Author(s): Okamoto I, Nakagawa K
  • Journal Title: Cancer Science Volume: 103(8) Pages: 1391-1396
  • Peer Reviewed
• [Journal Article] Clinical outcome for EML4-ALK–positive patients with advanced non–small cell lung cancer treated with first-line platinum-based chemotherapy. (2012)
  • Author(s): Takeda M, Okamoto I, Sakai K, Kawakami K, Nishio K, Nakagawa K.
  • Journal Title: Annals of Oncology Volume: 23(11) Pages: 2931-2936
  • Peer Reviewed
• [Journal Article] A novel mass spectrometry–based assay for diagnosis of EML4-ALK–positive non–small cell lung cancer. (2012)
  • Author(s): Sakai K, Okamoto I, Takezawa K, Hirashima T, Kaneda H, Takeda M, Matsumoto K, Kimura H, Fujita Y, Nakagawa K, Arao T, Nishio K.
  • Journal Title: Journal of Thoracic Oncology Volume: 7 Pages: 913-918
  • Peer Reviewed
• [Journal Article] Marked response to both S-1 and pemetrexed in a patient with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-positive lung adenocarcinoma. (2012)
  • Author(s): Kaneda H, Okamoto I, Sakai K, Tanizaki J, Takeda M, Nishio K, Nakagawa K.
  • Journal Title: Acta Oncologica Volume: 51(7) Pages: 942-944
  • Peer Reviewed
• [Journal Article] Clinical Outcome of Thoracic Radiotherapy for Locally Advanced NSCLC with EGFR Mutations or EML4-ALK. (2012)
  • Author(s): Hayashi H, Okamoto I, Kimura H, Sakai K, Nishimura Y, Nishio K, Nakagawa K.
  • Journal Title: Anticancer Research Volume: 32(10) Pages: 4533-4537
  • Peer Reviewed
• [Journal Article] Activation of HER family signaling as a mechanism of acquired resistance to ALK inhibitors in EML4-ALK-positive non-small cell lung cancer. (2012)
  • Author(s): Tanizaki J, Okamoto I, Okabe T, Sakai K, Tanaka K, Hayashi H, Kaneda H, Takezawa K, Kuwata K, Yamaguchi H, Hatashita E, Nishio K, Nakagawa K.
  • Journal Title: Clinical Cancer Research Volume: 18(22) Pages: 6219-6226
  • Peer Reviewed
• [Presentation] Multiplex genomic profiling of non-small cell lung cancer patients enrolled in the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin (WJOG6611LTR) (2014)
  • Author(s): H Yoshioka, I Okamoto, K Sakai, S Morita, H Kaneda, K Takeda, T Hirashima, Y Kogure, T Kimura, T Takahashi, S Atagi, T Seto, T Sawa, M Yamamoto, M Satouchi, M Okuno, S Nagase, K Nakagawa, Y Nakanishi, K Nishio
  • Organizer: ASCO Annual Meeting
  • Place of Presentation: Chicago
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] Biomarker analyses in clinical trials for NSCLC (2013)
  • Author(s): Isamu Okamoto
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台
• [Presentation] Clinical outcome for EML4-ALK-positive patients with advanced non-small cell lung cancer treated with first-line platinumbased chemotherapy. (2012)
  • Author(s): Masayuki Takeda, Isamu Okamoto, Kazuko Sakai, Hisato Kawakami, Kazuto Nishio, Kazuhiko Nakagawa.
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪府大阪市 大阪国際会議場
• [Presentation] MassARRAYによるEML4-ALK検出系の構築 (2012)
  • Author(s): 坂井 和子、岡本 勇、竹澤 健、平島 智徳、金田 裕靖、武田 真幸、松本 和子、木村 英晴、藤田 至彦、中川 和彦、荒尾 徳三、西尾 和人
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪府大阪市 大阪国際会議場