PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients

Perrone, Francesco; Lampis, Andrea; Orsenigo, Marta; Bartolomeo, Maria Di; Gevorgyan, Arpine; Losa, Marco; Frattini, Milo; Riva, Catherine; Andreola, Salvatore; Bajetta, Emilio; Bertario, Lucio; E, Leo; Pierotti, Marco A.; Pilotti, Silvana

doi:10.1093/annonc/mdn541

Cited by 370 publications

(304 citation statements)

References 26 publications

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“…First, we collected individual data on the ORR from 7 studies 6,13,14,18-21 that did not perform a comparison between patients with the KRAS p.G13D mutation and KRAS codon 12 mutations, which significantly increased the statistical power of the analysis. Second, except for 2 abstracts, 16,17 all fulltext studies 6,[13][14][15][18][19][20][21] were of high quality, with an average NOS score of 7. Third, no heterogeneity was observed in any comparison.…”

Section: Discussionmentioning

confidence: 99%

“…The articles were published between 2005 and 2011. Three studies 6,19,20 were conducted in France, 3 studies 13,18,21 were conducted in Italy, 1 study 14 was conducted in Switzerland, 1 study 17 was conducted in Figure 1. This is a flow chart of study selection for the current analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Cetuximab was received as first-line treatment in 1 study 17 and as firstline or subsequent treatment in 9 studies. 6,[13][14][15][16][18][19][20][21] Patients received cetuximab plus chemotherapy in 5 studies 14,16,17,19,21 and cetuximab-based treatment (cetuximab monotherapy or cetuximab plus chemotherapy) in the remaining 5 studies. 6,13,15,18,20 Quality-Assessment Results…”

Section: Methodsmentioning

confidence: 99%

“…Individual data were extracted from 7 studies 6,13,14,[18][19][20][21] that included the available data for ORR but did not perform a comparison between 2 groups of patients.…”

Section: Data Extractionmentioning

confidence: 99%

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KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer

Chen

Huang

Yang

et al. 2012

Cancer

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BACKGROUND:The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations. METHODS: Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies. RESULTS: Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54). CONCLUSIONS: Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution. Cancer 2013;119:714-21.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Individual data were extracted from 7 studies 6,13,14,[18][19][20][21] that included the available data for ORR but did not perform a comparison between 2 groups of patients.…”

Section: Data Extractionmentioning

confidence: 99%

See 2 more Smart Citations

KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer

Chen

Huang

Yang

et al. 2012

Cancer

View full text Add to dashboard Cite

show abstract

“…Concerning PIK3CA mutations, the first small series that have investigated their clinical impact on resistance to EGFR inhibitors in colorectal cancer were not very convincing as no significant correlation was observed between PIK3CA mutations and response to cetuximab or panitumumab, even if only one responder was reported among the nine mutated patients on the 92 patients included in three studies (Lievre et al, 2006;Moroni et al, 2008;Perrone et al, 2008). In a series of 110 patients treated with cetuximab or panitumumab, Sartore-Bianchi et al (2009) showed that exons 9 and 20 PIK3CA mutations (found in 13.6% of the cases) were correlated with the lack of response to anti-EGFR antibody in multivariate analysis after adjustment for KRAS mutation and PTEN loss of expression (odds ratio ¼ 0.11; 95% CI: 0.00-0.85; P ¼ 0.033).…”

Section: Pik3ca Mutations and Loss Of Pten Expressionmentioning

confidence: 99%