A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non―Small Cell Lung Cancer
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). Patients were...
Gespeichert in:
| Veröffentlicht in: | Clinical cancer research 2013-06, Vol.19 (11), p.3068-3077 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3077 |
|---|---|
| container_issue | 11 |
| container_start_page | 3068 |
| container_title | Clinical cancer research |
| container_volume | 19 |
| creator | SOCINSKI, Mark A GOLDMAN, Jonathan BONOMI, Philip BRAHMER, Julie CHEN, Lin-Chi SANDLER, Alan BELANI, Chandra P WEBB, Timothy HARPER, Harry HUBERMAN, Mark RAMALINGAM, Suresh WONG, Kwok-Kin EL-HARIRY, Iman TEOFILOVICI, Florentina WEI GUO SHAPIRO, Geoffrey I KOCZYWAS, Marianna VUKOVIC, Vojo HORN, Leora PASCHOLD, Eugene SALGIA, Ravi WEST, Howard SEQUIST, Lecia V |
| description | 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).
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.
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-naïve 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.
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. |
| doi_str_mv | 10.1158/1078-0432.CCR-12-3381 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3874465</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>23553849</sourcerecordid><originalsourceid>FETCH-LOGICAL-c441t-f0dbb6b0986d3c21827f21ef2fb482ac19a6fc4bf500476651a32fd1b0e7011b3</originalsourceid><addsrcrecordid>eNpVUctu1DAUtRCIPuATQN6wTPH1I3E2SKMUhpGmUFFYW3Zid4wyTmRnirJD6jfwg3wJjvoANvde6Twsn4PQKyBnAEK-BVLJgnBGz5rmSwG0YEzCE3QMQlQFo6V4mu8HzhE6Sek7IcCB8OfoiDIhmOT1Mbpd4YtDP_nWhslGfLnTyeLNBl9Nh27Gg8NrHexk0-gNvhjCMO1s1OOMfcCXevJZlfAPP-3w2mZwHn2r-37G59b5YDu86m50aPPxaQi_f_662mcUNzaP7SFc42YB4wv0zOk-2Zf3-xR9-_D-a_Ox2H5eb5rVtmg5h6lwpDOmNKSWZcdaCpJWjoJ11BkuqW6h1qVruXGCEF6VpQDNqOvAEFsRAMNO0bs73_Fg9rZbvhx1r8bo9zrOatBe_Y8Ev1PXw41isuK8FNlA3Bm0cUgpWveoBaKWVtSSuFoSV7kVBVQtrWTd638fflQ91JAJb-4JOuUAXcy5-PSXV3Eq66pmfwDfO5kY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non―Small Cell Lung Cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>SOCINSKI, Mark A ; GOLDMAN, Jonathan ; BONOMI, Philip ; BRAHMER, Julie ; CHEN, Lin-Chi ; SANDLER, Alan ; BELANI, Chandra P ; WEBB, Timothy ; HARPER, Harry ; HUBERMAN, Mark ; RAMALINGAM, Suresh ; WONG, Kwok-Kin ; EL-HARIRY, Iman ; TEOFILOVICI, Florentina ; WEI GUO ; SHAPIRO, Geoffrey I ; KOCZYWAS, Marianna ; VUKOVIC, Vojo ; HORN, Leora ; PASCHOLD, Eugene ; SALGIA, Ravi ; WEST, Howard ; SEQUIST, Lecia V</creator><creatorcontrib>SOCINSKI, Mark A ; GOLDMAN, Jonathan ; BONOMI, Philip ; BRAHMER, Julie ; CHEN, Lin-Chi ; SANDLER, Alan ; BELANI, Chandra P ; WEBB, Timothy ; HARPER, Harry ; HUBERMAN, Mark ; RAMALINGAM, Suresh ; WONG, Kwok-Kin ; EL-HARIRY, Iman ; TEOFILOVICI, Florentina ; WEI GUO ; SHAPIRO, Geoffrey I ; KOCZYWAS, Marianna ; VUKOVIC, Vojo ; HORN, Leora ; PASCHOLD, Eugene ; SALGIA, Ravi ; WEST, Howard ; SEQUIST, Lecia V</creatorcontrib><description>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).
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.
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-naïve 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.
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.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-12-3381</identifier><identifier>PMID: 23553849</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Female ; Gene Rearrangement ; Genotype ; HSP90 Heat-Shock Proteins - antagonists & inhibitors ; Humans ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Male ; Medical sciences ; Middle Aged ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Mutation ; Neoplasm Staging ; Pharmacology. Drug treatments ; Pneumology ; Receptor Protein-Tyrosine Kinases - genetics ; Treatment Outcome ; Triazoles - administration & dosage ; Triazoles - adverse effects ; Triazoles - therapeutic use ; Tumors ; Tumors of the respiratory system and mediastinum</subject><ispartof>Clinical cancer research, 2013-06, Vol.19 (11), p.3068-3077</ispartof><rights>2014 INIST-CNRS</rights><rights>2013 AACR</rights><rights>2013 American Association for Cancer Research. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-f0dbb6b0986d3c21827f21ef2fb482ac19a6fc4bf500476651a32fd1b0e7011b3</citedby><cites>FETCH-LOGICAL-c441t-f0dbb6b0986d3c21827f21ef2fb482ac19a6fc4bf500476651a32fd1b0e7011b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,3357,27928,27929</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27428979$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23553849$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SOCINSKI, Mark A</creatorcontrib><creatorcontrib>GOLDMAN, Jonathan</creatorcontrib><creatorcontrib>BONOMI, Philip</creatorcontrib><creatorcontrib>BRAHMER, Julie</creatorcontrib><creatorcontrib>CHEN, Lin-Chi</creatorcontrib><creatorcontrib>SANDLER, Alan</creatorcontrib><creatorcontrib>BELANI, Chandra P</creatorcontrib><creatorcontrib>WEBB, Timothy</creatorcontrib><creatorcontrib>HARPER, Harry</creatorcontrib><creatorcontrib>HUBERMAN, Mark</creatorcontrib><creatorcontrib>RAMALINGAM, Suresh</creatorcontrib><creatorcontrib>WONG, Kwok-Kin</creatorcontrib><creatorcontrib>EL-HARIRY, Iman</creatorcontrib><creatorcontrib>TEOFILOVICI, Florentina</creatorcontrib><creatorcontrib>WEI GUO</creatorcontrib><creatorcontrib>SHAPIRO, Geoffrey I</creatorcontrib><creatorcontrib>KOCZYWAS, Marianna</creatorcontrib><creatorcontrib>VUKOVIC, Vojo</creatorcontrib><creatorcontrib>HORN, Leora</creatorcontrib><creatorcontrib>PASCHOLD, Eugene</creatorcontrib><creatorcontrib>SALGIA, Ravi</creatorcontrib><creatorcontrib>WEST, Howard</creatorcontrib><creatorcontrib>SEQUIST, Lecia V</creatorcontrib><title>A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non―Small Cell Lung Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>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).
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.
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-naïve 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.
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.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Female</subject><subject>Gene Rearrangement</subject><subject>Genotype</subject><subject>HSP90 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Mutation</subject><subject>Neoplasm Staging</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Treatment Outcome</subject><subject>Triazoles - administration & dosage</subject><subject>Triazoles - adverse effects</subject><subject>Triazoles - therapeutic use</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctu1DAUtRCIPuATQN6wTPH1I3E2SKMUhpGmUFFYW3Zid4wyTmRnirJD6jfwg3wJjvoANvde6Twsn4PQKyBnAEK-BVLJgnBGz5rmSwG0YEzCE3QMQlQFo6V4mu8HzhE6Sek7IcCB8OfoiDIhmOT1Mbpd4YtDP_nWhslGfLnTyeLNBl9Nh27Gg8NrHexk0-gNvhjCMO1s1OOMfcCXevJZlfAPP-3w2mZwHn2r-37G59b5YDu86m50aPPxaQi_f_662mcUNzaP7SFc42YB4wv0zOk-2Zf3-xR9-_D-a_Ox2H5eb5rVtmg5h6lwpDOmNKSWZcdaCpJWjoJ11BkuqW6h1qVruXGCEF6VpQDNqOvAEFsRAMNO0bs73_Fg9rZbvhx1r8bo9zrOatBe_Y8Ev1PXw41isuK8FNlA3Bm0cUgpWveoBaKWVtSSuFoSV7kVBVQtrWTd638fflQ91JAJb-4JOuUAXcy5-PSXV3Eq66pmfwDfO5kY</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>SOCINSKI, Mark A</creator><creator>GOLDMAN, Jonathan</creator><creator>BONOMI, Philip</creator><creator>BRAHMER, Julie</creator><creator>CHEN, Lin-Chi</creator><creator>SANDLER, Alan</creator><creator>BELANI, Chandra P</creator><creator>WEBB, Timothy</creator><creator>HARPER, Harry</creator><creator>HUBERMAN, Mark</creator><creator>RAMALINGAM, Suresh</creator><creator>WONG, Kwok-Kin</creator><creator>EL-HARIRY, Iman</creator><creator>TEOFILOVICI, Florentina</creator><creator>WEI GUO</creator><creator>SHAPIRO, Geoffrey I</creator><creator>KOCZYWAS, Marianna</creator><creator>VUKOVIC, Vojo</creator><creator>HORN, Leora</creator><creator>PASCHOLD, Eugene</creator><creator>SALGIA, Ravi</creator><creator>WEST, Howard</creator><creator>SEQUIST, Lecia V</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20130601</creationdate><title>A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non―Small Cell Lung Cancer</title><author>SOCINSKI, Mark A ; GOLDMAN, Jonathan ; BONOMI, Philip ; BRAHMER, Julie ; CHEN, Lin-Chi ; SANDLER, Alan ; BELANI, Chandra P ; WEBB, Timothy ; HARPER, Harry ; HUBERMAN, Mark ; RAMALINGAM, Suresh ; WONG, Kwok-Kin ; EL-HARIRY, Iman ; TEOFILOVICI, Florentina ; WEI GUO ; SHAPIRO, Geoffrey I ; KOCZYWAS, Marianna ; VUKOVIC, Vojo ; HORN, Leora ; PASCHOLD, Eugene ; SALGIA, Ravi ; WEST, Howard ; SEQUIST, Lecia V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-f0dbb6b0986d3c21827f21ef2fb482ac19a6fc4bf500476651a32fd1b0e7011b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Female</topic><topic>Gene Rearrangement</topic><topic>Genotype</topic><topic>HSP90 Heat-Shock Proteins - antagonists & inhibitors</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Mutation</topic><topic>Neoplasm Staging</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Treatment Outcome</topic><topic>Triazoles - administration & dosage</topic><topic>Triazoles - adverse effects</topic><topic>Triazoles - therapeutic use</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SOCINSKI, Mark A</creatorcontrib><creatorcontrib>GOLDMAN, Jonathan</creatorcontrib><creatorcontrib>BONOMI, Philip</creatorcontrib><creatorcontrib>BRAHMER, Julie</creatorcontrib><creatorcontrib>CHEN, Lin-Chi</creatorcontrib><creatorcontrib>SANDLER, Alan</creatorcontrib><creatorcontrib>BELANI, Chandra P</creatorcontrib><creatorcontrib>WEBB, Timothy</creatorcontrib><creatorcontrib>HARPER, Harry</creatorcontrib><creatorcontrib>HUBERMAN, Mark</creatorcontrib><creatorcontrib>RAMALINGAM, Suresh</creatorcontrib><creatorcontrib>WONG, Kwok-Kin</creatorcontrib><creatorcontrib>EL-HARIRY, Iman</creatorcontrib><creatorcontrib>TEOFILOVICI, Florentina</creatorcontrib><creatorcontrib>WEI GUO</creatorcontrib><creatorcontrib>SHAPIRO, Geoffrey I</creatorcontrib><creatorcontrib>KOCZYWAS, Marianna</creatorcontrib><creatorcontrib>VUKOVIC, Vojo</creatorcontrib><creatorcontrib>HORN, Leora</creatorcontrib><creatorcontrib>PASCHOLD, Eugene</creatorcontrib><creatorcontrib>SALGIA, Ravi</creatorcontrib><creatorcontrib>WEST, Howard</creatorcontrib><creatorcontrib>SEQUIST, Lecia V</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SOCINSKI, Mark A</au><au>GOLDMAN, Jonathan</au><au>BONOMI, Philip</au><au>BRAHMER, Julie</au><au>CHEN, Lin-Chi</au><au>SANDLER, Alan</au><au>BELANI, Chandra P</au><au>WEBB, Timothy</au><au>HARPER, Harry</au><au>HUBERMAN, Mark</au><au>RAMALINGAM, Suresh</au><au>WONG, Kwok-Kin</au><au>EL-HARIRY, Iman</au><au>TEOFILOVICI, Florentina</au><au>WEI GUO</au><au>SHAPIRO, Geoffrey I</au><au>KOCZYWAS, Marianna</au><au>VUKOVIC, Vojo</au><au>HORN, Leora</au><au>PASCHOLD, Eugene</au><au>SALGIA, Ravi</au><au>WEST, Howard</au><au>SEQUIST, Lecia V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non―Small Cell Lung Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>19</volume><issue>11</issue><spage>3068</spage><epage>3077</epage><pages>3068-3077</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>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).
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.
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-naïve 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.
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><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>23553849</pmid><doi>10.1158/1078-0432.CCR-12-3381</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2013-06, Vol.19 (11), p.3068-3077 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3874465 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Antineoplastic agents Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Biological and medical sciences Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology Female Gene Rearrangement Genotype HSP90 Heat-Shock Proteins - antagonists & inhibitors Humans Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - pathology Male Medical sciences Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Mutation Neoplasm Staging Pharmacology. Drug treatments Pneumology Receptor Protein-Tyrosine Kinases - genetics Treatment Outcome Triazoles - administration & dosage Triazoles - adverse effects Triazoles - therapeutic use Tumors Tumors of the respiratory system and mediastinum |
| title | A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non―Small Cell Lung Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T03%3A55%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Multicenter%20Phase%20II%20Study%20of%20Ganetespib%20Monotherapy%20in%20Patients%20with%20Genotypically%20Defined%20Advanced%20Non%E2%80%95Small%20Cell%20Lung%20Cancer&rft.jtitle=Clinical%20cancer%20research&rft.au=SOCINSKI,%20Mark%20A&rft.date=2013-06-01&rft.volume=19&rft.issue=11&rft.spage=3068&rft.epage=3077&rft.pages=3068-3077&rft.issn=1078-0432&rft.eissn=1557-3265&rft.coden=CCREF4&rft_id=info:doi/10.1158/1078-0432.CCR-12-3381&rft_dat=%3Cpubmed_cross%3E23553849%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/23553849&rfr_iscdi=true |