ASCO Annual Meeting 2012 PHASE II STUDY OF PANITUMUMAB (P) PHASE II STUDY OF PANITUMUMAB (P) IN COMBINATION WITH FOLFOXIRI AS IN COMBINATION WITH FOLFOXIRI AS FIRST-LINE TREATMENT FIRST-LINE TREATMENT OF METASTATIC COLORECTAL CANCER OF METASTATIC COLORECTAL CANCER (MCRC): HIGH ACTIVITY IN MOLECULARLY (MCRC): HIGH ACTIVITY IN MOLECULARLY SELECTED PATIENTS (PTS). SELECTED PATIENTS (PTS). Sara Lonardi 1 , Lorenzo Fornaro 2 , Francesca Bergamo 1 , Marta Schirripa 2 , Giuseppe Aprile 3 , Manfredi Morvillo 2 , Gianluca Masi 2 , Fotios Loupakis 2 , Lorenzo Calvetti 1 , Chiara Cremolini 2 , Lisa Salvatore 2 , Alberto Zaniboni 4 , Vittorina Zagonel 1 , Alfredo Falcone 2 ; 1 Oncologia Medica 1, Istituto Oncologico Veneto - IRCCS, Padova, Italy; 2 Oncologia Medica 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy; 3 Oncologia Medica, Azienda Ospedaliero-Universitaria, Udine, Italy; 4 Oncologia Medica, Casa di Cura Poliambulanza, Brescia, Italy
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ASCO Annual Meeting 2012 PHASE II STUDY OF PANITUMUMAB (P) IN COMBINATION WITH FOLFOXIRI AS FIRST-LINE TREATMENT OF METASTATIC COLORECTAL CANCER (MCRC):
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ASCO Annual Meeting 2012
PHASE II STUDY OF PANITUMUMAB (P) PHASE II STUDY OF PANITUMUMAB (P) IN COMBINATION WITH FOLFOXIRI AS IN COMBINATION WITH FOLFOXIRI AS
FIRST-LINE TREATMENT FIRST-LINE TREATMENT OF METASTATIC COLORECTAL CANCER OF METASTATIC COLORECTAL CANCER
(MCRC): HIGH ACTIVITY IN MOLECULARLY (MCRC): HIGH ACTIVITY IN MOLECULARLY SELECTED PATIENTS (PTS). SELECTED PATIENTS (PTS).
Sara Lonardi1, Lorenzo Fornaro2, Francesca Bergamo1, Marta Schirripa2, Giuseppe Aprile3, Manfredi Morvillo2, Gianluca Masi2, Fotios Loupakis2, Lorenzo Calvetti1, Chiara
Cremolini2, Lisa Salvatore2, Alberto Zaniboni4, Vittorina Zagonel1, Alfredo Falcone2;
Mutations in other KRAS codons (such as codon 61) and other members of the RAS family (mainly HRAS and NRAS) may predict resistance to anti-EGFR agents.
De Roock W, Lancet Oncol 2010
BRAF V600E mutation may predict resistance to anti-EGFR agents.Di Nicolantonio F, J Clin Oncol 2008
• Availability of formalin-fixed paraffin embedded tumor block from primary or metastasis
• RAS and BRAF wild-type status of primary colorectal cancer or related metastasis
• Unresectable and measurable metastatic disease (RECIST criteria)
• Adjuvant chemotherapy ended more than 12 months before relapse
• Age ≥ 18 years and ≤ 75 years
• ECOG PS ≤ 2 if aged < 71 years and ECOG PS = 0 if aged 71-75 years
• Adequate hematological, liver and kidney function
• Prior palliative chemotherapy
• Prior treatment with EGFR inhibitors
• Symptomatic peripheral neuropathy ≥ 2 grade according to NCIC-CTG criteria
Main Enrollment CriteriaMain Enrollment Criteria
Study Objective and End-pointsStudy Objective and End-points
The objective of the trial is to investigate the activity of FOLFOXIRI + panitumumab as first-line treatment in KRAS, NRAS, HRAS and BRAF wild-type mCRC patients.
The objective of the trial is to investigate the activity of FOLFOXIRI + panitumumab as first-line treatment in KRAS, NRAS, HRAS and BRAF wild-type mCRC patients.
PRIMARY END-POINT:PRIMARY END-POINT:
Response Rate
SECONDARYSECONDARY END-POINTS: Progression Free Survival Secondary R0 surgery of metastases Overall survival Safety profile Analyses of potential predictive factors of treatment activity or efficacy
The primary study end-point is Response rate (RECIST vers. 1.1)
Mini-max, two-stage design by Simon
• alpha and beta errors of 0.05 and 0.20, respectively
• p0 (RR in null hypothesis) of 0.60
• p1 (RR in alternative hypothesis) of 0.80
A total of 35 evaluable patients will be enrolled (considering an incidence of RAS and BRAF mutations around 50%, a total of around 70 patients should be screened)
If at least 26 response will be observed, the treatment will be considered promising
Median follow up: 12.2 monthsNo. of pts: 37No. of events: 24Median PFS: 10.8 months
- Combining a triple drug regimen such as FOLFOXIRI with Panitumumab seems feasible.
- However, treatment is associated with a relatively high incidence of severe mucosal toxicity (mainly diarrhea), therefore, a reduced dose of 5-FU and irinotecan compared with standard GONO-FOLFOXIRI is required.
- The primary end-point was met: in molecularly selected patients, FOLFOXIRI-Panitumumab achieved an ORR > 90%, leading to radical resection of metastases in 32% of the patients.
- Median PFS appears promising (mPFS: 10.8 months), while mOS has not been reached at a median follow-up of 12.2 months.