Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE, a global phase 3 study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F18%3A00078085" target="_blank" >RIV/00209805:_____/18:00078085 - isvavai.cz</a>

Result on the web

<a href="https://academic.oup.com/annonc/advance-article/doi/10.1093/annonc/mdy461/5136414" target="_blank" >https://academic.oup.com/annonc/advance-article/doi/10.1093/annonc/mdy461/5136414</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/annonc/mdy461" target="_blank" >10.1093/annonc/mdy461</a>

Result language

angličtina

Original language name

Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE, a global phase 3 study

Original language description

BACKGROUND: Second-line treatment with ramucirumab+FOLFIRI improved overall survival (OS) versus placebo+FOLFIRI for patients with metastatic colorectal carcinoma (mCRC) (hazard ratio [HR]=0.84, 95%CI=0.73-0.98, P=0.022). Post-hoc analyses of RAISE patient data examined the association of RAS/RAF mutation status and the anatomical location of the primary CRC tumour (left versus right) with efficacy parameters. PATIENTS AND METHODS: Patient tumour tissue was classified as BRAF mutant, KRAS/NRAS (&quot;RAS&quot;) mutant, or RAS/BRAF wild-type. Left-CRC was defined as the splenic flexure, descending and sigmoid colon, and rectum; right-CRC included transverse, ascending colon and cecum. RESULTS: RAS/RAF mutation status was available for 85% of patients (912/1072) and primary tumour location was known for 94.4% of patients (1012/1072). A favourable and comparable ramucirumab treatment effect was observed for patients with RAS mutations (OS HR = 0.86, 95% CI = 0.71-1.04) and patients with RAS/BRAF wild-type tumours (OS HR = 0.86, 95% CI = 0.64-1.14). Among the 41 patients with BRAF-mutated tumours, the ramucirumab benefit was more notable (OS HR = 0.54, 95% CI = 0.25-1.13), although, as with the other genetic subgroup analyses, differences were not statistically significant. Progression-free survival (PFS) data followed the same trend. Treatment-by-mutation status interaction tests (OS P=0.523, PFS P=0.655) indicated that the ramucirumab benefit was not statistically different among the mutation subgroups, although the small sample size of the BRAF group limited the analysis. Addition of ramucirumab to FOLFIRI improved left-CRC median OS by 2.5 month over placebo (HR = 0.81, 95% CI = 0.68-0.97); median OS for ramucirumab-treated patients with right-CRC was 1.1 month over placebo (HR = 0.97, 95% CI = 0.75-1.26). The treatment-by-subgroup interaction was not statistically significant for tumour sidedness (P = 0.276). CONCLUSIONS: In the RAISE study, the addition of ramucirumab to FOLFIRI improved patient outcomes, regardless of RAS/RAF mutation status and tumour sidedness. Ramucirumab treatment provided a numerically substantial benefit in BRAF-mutated tumours, although the p-values were not statistically significant. ClinicalTrials.gov, NCT01183780.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Annals of oncology

ISSN

0923-7534

e-ISSN

—

Volume of the periodical

30

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

124-131

UT code for WoS article

000459677700018

EID of the result in the Scopus database

2-s2.0-85060163908