Konference: 2015 40th Congress ESMO a 18th ECCO - účast ČR
Kategorie: Kolorektální karcinom
Téma: Postery
Číslo abstraktu: P098/2108
Autoři: Eric Van Cutsem; doc. MUDr. Radka Obermannová, Ph.D.; M.D. György Bodoky, Ph.D.; Doc. MUDr. Jana Prausová, Ph.D., MBA; Rocio García-Carbonero; Tudor Ciuleanu; Pilar Garcia Alfonso; David Portnoy, M.D.; Allen Lee Cohn, M.D.; Kentaro Yamazaki; Prof. Philip Clingan; Takayuki Yoshino; Jonathan Polikoff, M.D.; Sara Lonardi; Teresa Macarulla, MD; Ling Yang; Federico Nasroulah
Background: Ramucirumab (RAM) is a recombinant human IgG1 monoclonal antibody that binds to the extracellular domain of VEGFR-2, preventing ligand binding and receptor activation. In the completed phase 3 RAISE trial (NCT01183780, sponsor Eli Lilly and Company), adding RAM to FOLFIRI demonstrated a survival benefit for patients with metastatic colorectal carcinoma (mCRC) with progression on or after first-line combination therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. KRAS mutations occur in 40–50% of CRC tumors and may contribute to tumorigenesis and upregulate angiogenesis. This analysis evaluates the efficacy and safety of RAM+FOLFIRI in RAISE by KRAS subgroup.
Materials and Methods: Patients enrolled in RAISE were stratified by KRAS status (wild-type vs. mutant), geography, and time to first-line PD, and then randomized 1:1 to RAM 8mg/kg IV+FOLFIRI every 2 weeks (Q2W) or placebo (PBO)+FOLFIRI Q2W. Overall survival (OS) and progression-free survival (PFS) of KRAS subgroups were evaluated by Kaplan–Meier. Hazard ratio (HR) was calculated by unstratified Cox proportional hazards model; P-value was calculated by unstratified log rank test. The interaction was tested to determine if treatment effect was consistent between KRAS subgroups. Treatment-emergent adverse events (TEAEs) were compared between treatment arms by KRAS subgroup.
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KRAS Wild-type |
KRAS Mutant |
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|
|
RAM+FOLFIRI (N=267) |
PBO+FOLFIRI (N=275) |
RAM+FOLFIRI (N=269) |
PBO+FOLFIRI (N=261) |
|
Overall survival (OS) |
||||
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OS median |
14.39 |
11.86 |
12.71 |
11.33 |
|
(95%CI) |
(12.65,16.07) |
(10.84,13.34) |
(11.56,13.96) |
(10.58,12.94) |
|
Hazard ratio, unstratified |
0.815 |
0.893 |
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|
(95%CI) |
(0.67,1.00) |
(0.73,1.09) |
||
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Log rank p-value, unstratified |
0.049 |
0.263 |
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Interaction p-value |
0.505 |
|||
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Progression-free survival (PFS) |
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PFS median |
5.65 |
4.70 |
5.62 |
4.30 |
|
(95%CI) |
(5.45,6.18) |
(4.24,5.55) |
(5.09,6.80) |
(4.14,5.36) |
|
Hazard ratio, unstratified |
0.77 |
0.84 |
||
|
(95%CI) |
(0.65,0.92) |
(0.70,1.00) |
||
|
Log rank p-value, unstratified |
0.004 |
0.056 |
||
|
Interaction p-value |
0.526 |
|||
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Safety Population |
N=263 |
N=269 |
N=266 |
N=259 |
|
Patients with ≥1 TEAE |
|
|
|
|
|
Any grade, n (%) |
260 (98.9) |
264 (98.1) |
262 (98.5) |
255 (98.5) |
|
Grade ≥3, n (%) |
204 (77.6)* |
170 (63.2) |
214 (80.5)* |
159 (61.4) |
*p<0.05 between treatment group comparison, Fisher's exact test.
Results: Within each KRAS subgroup, baseline patient and tumor characteristics were well balanced between treatment groups. Median OS and PFS were greater for patients receiving RAM+FOLFIRI in both KRAS subgroups, compared with patients receiving PBO+FOLFIRI (Table). OS and PFS treatment benefit was not statistically different between patient groups defined by KRAS status, demonstrated by lack of treatment-by-subgroup interaction. RAM+FOLFIRI was well tolerated in KRAS wild-type and mutant subgroups.
Conclusions: Median OS was greater for patients receiving RAM+FOLFIRI vs PBO+FOLFIRI overall, with a consistent treatment effect irrespective of tumor KRAS status. Safety results were similar between KRAS subgroups in the RAISE population.
Conflict of interest: Advisory Board: Gyorgy Bodoky – Eli Lilly and Company. Rocio Garcia-Carbonero – Eli Lilly and Company, Roche, Sanofi, Merck, Amgen, Novartis, Bayer, Ipsen. Tudor Ciuleanu – Eli Lilly and Company, Pfizer, Roche, Merck, MSD, BMS, Sandoz, Janssen, Astellas, Amgen, Novartis, Astra Zeneca. Radka Obermannova – Eli Lilly and Company. Corporate-sponsored Research: Eric Van Cutsem – Eli Lilly and Company, Amgen, Bayer, Boehringer, Celgene, Merckserono, Novartis, Roche, Sanofi. Radka Obermannova, Gyorgy Bodoky, Jana Prausova, Rocio Garcia-Carbonero, Tudor Ciuleanu, Pilar Garcia Alfonso, David Portnoy, Allen Cohn, Kentaro Yamazaki, Phil Clingan, Takayuki Yoshino, Jonathon Polikoff, Sara Lonardi, Teresa Macarulla – Eli Lilly and Company. Other Substantive Relationships: Ling Yang and Federico Nasroulah – Employee and shareholder, Eli Lilly and Company.
colorectal carcinoma
Ramucirumab
KRAS
Datum přednesení příspěvku: 27. 9. 2015
