Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies
Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment effic...
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| Veröffentlicht in: | Annals of oncology 2017-08, Vol.28 (8), p.1862-1868 |
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| creator | Boeckx, N. Koukakis, R. Op de Beeck, K. Rolfo, C. Van Camp, G. Siena, S. Tabernero, J. Douillard, J.-Y. André, T. Peeters, M. |
| description | Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors.
Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided.
Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125).
The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted.
PRIME (NCT00364013), PEAK (NCT00819780). |
| doi_str_mv | 10.1093/annonc/mdx119 |
| format | Article |
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Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided.
Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125).
The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted.
PRIME (NCT00364013), PEAK (NCT00819780).</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdx119</identifier><identifier>PMID: 28449055</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Antibodies, Monoclonal - therapeutic use ; Antineoplastic Agents, Immunological - therapeutic use ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Female ; first-line ; Genes, ras ; Humans ; Male ; metastatic colorectal cancer ; Middle Aged ; Neoplasm Metastasis ; Original ; Panitumumab ; Prognosis ; Randomized Controlled Trials as Topic ; RAS wild-type ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; tumor sidedness</subject><ispartof>Annals of oncology, 2017-08, Vol.28 (8), p.1862-1868</ispartof><rights>2017 THE AUTHORS</rights><rights>The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.</rights><rights>The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-fd3daa7d517a82e8ebbfe9d52f833ee6e72344ea208007f3ff6a3066a1ee5c0d3</citedby><cites>FETCH-LOGICAL-c501t-fd3daa7d517a82e8ebbfe9d52f833ee6e72344ea208007f3ff6a3066a1ee5c0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28449055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boeckx, N.</creatorcontrib><creatorcontrib>Koukakis, R.</creatorcontrib><creatorcontrib>Op de Beeck, K.</creatorcontrib><creatorcontrib>Rolfo, C.</creatorcontrib><creatorcontrib>Van Camp, G.</creatorcontrib><creatorcontrib>Siena, S.</creatorcontrib><creatorcontrib>Tabernero, J.</creatorcontrib><creatorcontrib>Douillard, J.-Y.</creatorcontrib><creatorcontrib>André, T.</creatorcontrib><creatorcontrib>Peeters, M.</creatorcontrib><title>Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors.
Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided.
Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125).
The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted.
PRIME (NCT00364013), PEAK (NCT00819780).</description><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antineoplastic Agents, Immunological - therapeutic use</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Female</subject><subject>first-line</subject><subject>Genes, ras</subject><subject>Humans</subject><subject>Male</subject><subject>metastatic colorectal cancer</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Original</subject><subject>Panitumumab</subject><subject>Prognosis</subject><subject>Randomized Controlled Trials as Topic</subject><subject>RAS wild-type</subject><subject>Retrospective Studies</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>tumor sidedness</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1vFSEUhidGY6_VpVvD0s1YGIb5cGFiGr-SJrrQNTkXDi1mgCuHadXf4w-Vm6mNLlyRcJ68HN6naZ4K_kLwWZ5BjCmas2C_CzHfa3ZCDXM78V7cb3Z87mQ7KtmfNI-IvnLOh7mbHzYn3dT3M1dq1_z6lH2A_IOVNaTMyFu0EYnYFRCDyHw4gCksRXbI6TIm8sdry0pGKAFjHa3FpIDMRxawABUo3jCTlpTRFFiYgWgwv2QZaV0KMZdTYOUmsVyDUvA_0TLnM5V28RHZAaKvy6wB9ozKaj3S4-aBg4Xwye152nx5--bz-fv24uO7D-evL1qjuCits9ICjFaJEaYOJ9zvHc5WdW6SEnHAsZN9j9DxifPRSecGkHwYQCAqw608bV5tuYd1H9Ca-r0Miz5sFekEXv87if5KX6ZrrSbZ81HWgOe3ATl9W5GKDp4MLgtETCtpMc1SKa6EqGi7oSYnoozu7hnB9dGs3szqzWzln_292x39R2UFxg3A2tC1x6zJeKzVW38UoW3y_4n-DTlBvLA</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Boeckx, N.</creator><creator>Koukakis, R.</creator><creator>Op de Beeck, K.</creator><creator>Rolfo, C.</creator><creator>Van Camp, G.</creator><creator>Siena, S.</creator><creator>Tabernero, J.</creator><creator>Douillard, J.-Y.</creator><creator>André, T.</creator><creator>Peeters, M.</creator><general>Elsevier Ltd</general><general>Oxford University Press</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170801</creationdate><title>Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies</title><author>Boeckx, N. ; 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The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors.
Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided.
Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125).
The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted.
PRIME (NCT00364013), PEAK (NCT00819780).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28449055</pmid><doi>10.1093/annonc/mdx119</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Antibodies, Monoclonal - therapeutic use Antineoplastic Agents, Immunological - therapeutic use Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Female first-line Genes, ras Humans Male metastatic colorectal cancer Middle Aged Neoplasm Metastasis Original Panitumumab Prognosis Randomized Controlled Trials as Topic RAS wild-type Retrospective Studies Survival Analysis Treatment Outcome tumor sidedness |
| title | Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies |
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