A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non–Small Cell Lung Cancer
Mark A. Socinski,Jonathan H. Goldman,Iman El-Hariry,Marianna Koczywas,V. Vukovic,Leora Horn,Eugene Paschold,Ravi Salgia,Howard West,Lecia V. Sequist,Philip Bonomi,Julie R. Brahmer,Lin-Chi Chen,Alan Sandler,Chandra P. Belani,Timothy Webb,Harry D. Harper,Mark S. Huberman,Suresh S. Ramalingam,Kwok-Kin Wong,Florentina Teofilovici,Wei Guo,Geoffrey I. Shapiro +22 more
TLDR
Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement.Abstract:
Purpose: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non–small cell lung cancer (NSCLC). Experimental Design: Patients were enrolled into cohort A (mutant EGFR ), B (mutant KRAS ), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m 2 ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. Results: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A ( n = 15), B ( n = 17), or C ( n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase ( ALK ) gene rearrangement, retrospectively detected by FISH ( n = 1) or PCR-based assays ( n = 3), in crizotinib-naive patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia. Conclusions: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement. Clin Cancer Res; 19(11); 3068–77. ©2013 AACR .read more
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Broad targeting of resistance to apoptosis in cancer.
Ramzi M. Mohammad,Irfana Muqbil,Leroy Lowe,Clement G. Yedjou,Hsue-Yin Hsu,Liang Tzung Lin,Markus D. Siegelin,Carmela Fimognari,Nagi B. Kumar,Q. Ping Dou,Huanjie Yang,Abbas Samadi,Gian Luigi Russo,Carmela Spagnuolo,Swapan K. Ray,Mrinmay Chakrabarti,James D. Morre,Helen M. Coley,Kanya Honoki,Hiromasa Fujii,Alexandros G. Georgakilas,Amedeo Amedei,Elena Niccolai,Amr Amin,S. Salman Ashraf,William G. Helferich,Xujuan Yang,Chandra S. Boosani,Gunjan Guha,Dipita Bhakta,Maria Rosa Ciriolo,Katia Aquilano,Sophie Chen,Sulma I. Mohammed,W. Nicol Keith,Alan Bilsland,Dorota Halicka,Somaira Nowsheen,Asfar S. Azmi +38 more
TL;DR: This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.
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Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach
TL;DR: The roles of some of the important HSPs in cancer are reviewed, and how targeting them could be efficacious, especially when traditional cancer therapies fail are reviewed.
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Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment
Evguenia M. Alexandrova,Alisha R. Yallowitz,Dun Li,S Xu,Ramona Schulz,D. A. Proia,Guillermina Lozano,Matthias Dobbelstein,Ute M. Moll +8 more
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References
More filters
Journal ArticleDOI
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)
Elizabeth Eisenhauer,P. Therasse,Jan Bogaerts,Lawrence H. Schwartz,Daniel J. Sargent,Robert Ford,Janet Dancey,S. Arbuck,S. Gwyther,Margaret M. Mooney,Larry Rubinstein,Lalitha K. Shankar,Lori E. Dodd,Robert M. Kaplan,Denis Lacombe,Jaap Verweij +15 more
TL;DR: The revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions, and a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included.
Journal ArticleDOI
Cancer statistics, 2012
TL;DR: The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer, which can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket.
Journal ArticleDOI
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Manabu Soda,Young Lim Choi,Munehiro Enomoto,Shuji Takada,Yoshihiro Yamashita,Shunpei Ishikawa,Shin-ichiro Fujiwara,Hideki Watanabe,Kentaro Kurashina,Hisashi Hatanaka,Masashi Bando,Shoji Ohno,Yuichi Ishikawa,Hiroyuki Aburatani,Toshiro Niki,Yasunori Sohara,Yukihiko Sugiyama,Hiroyuki Mano +17 more
TL;DR: It is shown that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells.
Journal ArticleDOI
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Eunice L. Kwak,Yung-Jue Bang,D. Ross Camidge,Alice T. Shaw,Benjamin Solomon,Robert G. Maki,Sai-Hong Ignatius Ou,Bruce J. Dezube,Pasi A. Jänne,Daniel B. Costa,Marileila Varella-Garcia,Woo-Ho Kim,Thomas J. Lynch,Panos Fidias,Hannah Stubbs,Jeffrey A. Engelman,Lecia V. Sequist,Weiwei Tan,Leena Gandhi,Mari Mino-Kenudson,Greg C. Wei,S. Martin Shreeve,Mark J. Ratain,Jeffrey Settleman,James G. Christensen,Daniel A. Haber,Keith D. Wilner,Ravi Salgia,Geoffrey I. Shapiro,Jeffrey W. Clark,A. John Iafrate +30 more
TL;DR: The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients, and the drug resulted in grade 1 or 2 gastrointestinal side effects.
Journal ArticleDOI
Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer
Giorgio V. Scagliotti,Purvish M. Parikh,Joachim von Pawel,Bonne Biesma,Johan Vansteenkiste,Christian Manegold,Piotr Serwatowski,Ulrich Gatzemeier,Raghunadharao Digumarti,Mauro Zukin,Jin S. Lee,Anders Mellemgaard,Keunchil Park,Shehkar Patil,Janusz Rolski,Tuncay Göksel,Filippo de Marinis,Lorinda Simms,Katherine P. Sugarman,David R. Gandara +19 more
TL;DR: This is the first prospective phase III study in NSCLC to show survival differences based on histologic type and cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cis platin/gemcitabine.
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