Final results from a randomized phase 3 study of FOLFIRI ± panitumumab for second-line treatment of metastatic colorectal cancer

Peeters, Marc; Price, Tim; Cervantes, Andrés; Sobrero, Alberto; Ducreux, Michel; Hotko, Yevhen; André, Thierry; Chan, Emily; Lordick, Florian; Punt, Cornelis J.A.; Strickland, A. H.; Wilson, Gregory; Ciuleanu, Tudor-Eliade; Roman, L.; Cutsem, Éric Van; Tian, Yong‐Sheng; Sidhu, Roger

doi:10.1093/annonc/mdt523

Cited by 190 publications

(133 citation statements)

References 27 publications

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“…Among all RAS wild-type (KRAS at exon 2, 3, 4 and NRAS 2, 3, 4) patients, benefits were observed in PFS when treated with FOLFIRI/panitumumab versus FOLFIRI alone as second-line treatment (17). Similar to results in other studies, the addition of an anti-EGFR therapy to standard chemotherapy provided no statistically significant benefit in terms of OS, PFS, or RR in the presence of any RAS mutation.…”

Section: Primary and Acquired Resistance To Biologic Therapies In Gassupporting

confidence: 70%

“…Treatment with anti-EGFR therapy did not significant improve median PFS or OS. FOLFIRI/ panitumumab versus FOLFIRI alone was examined in the second-line setting by Peeters and colleagues (17). The presence of a BRAF mutation resulted in no significant differences in PFS or OS whether patients were treated with FOLFIRI/panitumumab or FOLFIRI alone, indicating BRAF mutations may confer EGFR therapy resistance although this study was not powered for this purpose.…”

Section: Brafmentioning

confidence: 99%

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Primary and acquired resistance to biologic therapies in gastrointestinal cancers

Lubner

Uboha

Deming

2017

J. Gastrointest. Oncol.

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Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds.Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways. Resistance to EGFR inhibitors: primaryAs many tumors of the gastrointestinal tract arise from epithelial origins, the attractiveness of treating with therapies blocking EGFR is readily evident. A series of colon cancer trials have shown, improvements in RRs and OS, particularly in populations without mutations in EGFR and/or downstream effectors, which are described in the next section. In most other GI cancers, however, blocking EGFR has not demonstrated clinically relevant improvements in outcome (2-4). New strategies to investigate anti-EGFR therapy in other tumor types are focusing on selecting for patients whose tumors overexpress EGFR, or do not harbor deleterious mutations (ENRICH study, NCT 01813253) (5). KRAS/NRASKRAS and NRAS belong to the family of RAS oncogenes.

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Section: Primary and Acquired Resistance To Biologic Therapies In Gassupporting

confidence: 70%

Section: Brafmentioning

confidence: 99%

Primary and acquired resistance to biologic therapies in gastrointestinal cancers

Lubner

Uboha

Deming

2017

J. Gastrointest. Oncol.

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“…Im Vergleich zur alleinigen Chemotherapie wurde durch Zugabe eines anti-EGFR-Antikörpers keine Verbesserung von PFS (HR 1,12, p = 0,20) oder OS (HR 1,08, p = 0,14) beobachtet. Vergleichbare Daten wurden für das Gesamtüberleben auch in der Zweitlinientherapie (OS: HR 0,93, p = 0,482) gefunden [1046]. Bei intensiv vorbehandelten Patienten und Vorliegen einer KRAS-Mutation konnte durch Cetuximab im Vergleich zu "best supportive care" (BSC) kein Überlebensvorteil erreicht werden (HR 1,01, p = 0,97), während eine hochgsignifikante OS-Verlänge-rung bei Patienten mit KRAS-Wildtyp-Tumoren beobachtet wurde (HR 0,55, p < 0,001) [1047].…”

Section: Ras-mutationunclassified

S3-Leitlinie – Kolorektales Karzinom

Schmiegel

Buchberger

Follmann³

et al. 2017

Z Gastroenterol

147

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“…In the second-line setting, panitumumab has been tested in combination with FOLIFIRI versus FOLFIRI alone in KRAS wild-type patients. This trial demonstrated an improvement in PFS for patients treated with the combination (6.7 vs 4.9 months; HR: 0.82; p = 0.0023) and a trend toward longer OS but without statistical significance [69]. The need for a more precise selection of mCRC patient candidates for anti-EGFR treatment has been confirmed by the analysis of the results of the FIRE-3 trial, in which 592 KRAS wild-type mCRC patients were randomised to receive FOLFIRI plus either cetuximab or bevacizumab as first-line treatment.…”

Section: Anti-egfr (Cetuximab Panitumumab)mentioning

confidence: 84%

Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario

Bronte

Sortino

Passiglia

et al. 2014

Expert Opinion on Biological Therapy

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Final results from a randomized phase 3 study of FOLFIRI ± panitumumab for second-line treatment of metastatic colorectal cancer

Cited by 190 publications

References 27 publications

Primary and acquired resistance to biologic therapies in gastrointestinal cancers

Primary and acquired resistance to biologic therapies in gastrointestinal cancers

S3-Leitlinie – Kolorektales Karzinom

Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario

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