Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer

Peeters, Marc; Price, Tim; Cervantes, Andrés; Sobrero, Alberto; Ducreux, Michel; Hotko, Yevhen; Thewis, André; Chan, Emily; Lordick, Florian; Punt, Cornelis J.A.; Strickland, A. H.; Wilson, Gregory; Ciuleanu, Tudor-Eliade; Roman, L.; Cutsem, Éric Van; Tzekova, Valentina; Collins, Simon; Oliner, Kelly S.; Rong, Alan; Gansert, Jennifer

doi:10.1200/jco.2009.27.6055

Cited by 906 publications

(626 citation statements)

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“…Furthermore, the efficacy of second-line cetuximab plus irinotecan in the present study (ORR 45.0%, PFS 8.3 months) was very promising compared to that in previous studies involving second-line aflibercept (RR 19.8%, PFS 6.9 months) (25) or panitumumab (RR 35%, PFS 5.9 months). (26) In the present study, the median OS from the second-line treatments was 18.3 months for arm A, 12.6 months for arm B and 12.9 months for arm C, respectively, and there was a trend favoring arm A without statistical significance (P = 0.138, Fig. 2C,D).…”

Section: Discussionsupporting

confidence: 47%

“…(25,26) The present study involved patients who became refractory to first-line irinotecan plus fluoropyrimidines. Second-line treatment strategies were compared according to KRAS geno- type: patients with mutant KRAS followed crossover cytotoxic doublet regimens of FOLFOX or CapeOX, and those with wildtype KRAS followed second-line cetuximab plus irinotecan or FOLFOX or CapeOX regimens.…”

Section: Discussionmentioning

confidence: 99%

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Second‐line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild‐type KRAS

et al. 2013

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The goal of the present study was to compare the efficacy of the combination of cetuximab and irinotecan to the combination of oxaliplatin and fluoropyrimidines as second-line chemotherapy in patients with irinotecan-refractory and oxaliplatin-na€ ıve metastatic colorectal cancer (mCRC) harboring wild-type KRAS. The study included 120 patients with mCRC who had progressed after irinotecan-containing first-line chemotherapy and were never treated with oxaliplatin; 40 patients with wild-type KRAS were accrued prospectively in the experimental arm (arm A), and 80 patients accrued retrospectively were divided into control arms B (n = 46) and C (n = 34) according to KRAS genotype. Second-line treatments consisted of cetuximab plus irinotecan for arm A, and oxaliplatin plus either 5-fluorouracil (FOLFOX) or capecitabine (CapeOX) for the control arms. The median progression-free survival (PFS) was 8.3, 5.8 and 3.9 months, for arms A, B and C, respectively, with statistical significance favoring arm A (P = 0.007). Differences in overall survival did not reach statistical significance (18.3 vs 12.6 vs 12.9, P = 0.138), although there was a trend toward longer overall survival in arm A. In terms of benefit from oxaliplatin-containing regimens either as second-line or third-line therapy, the median PFS was 5.0 months in arms B and C as second-line therapy, and 4.0 months in arm A as third-line therapy, with no statistical significance (P = 0.385). Second-line cetuximab plus irinotecan is a valid treatment strategy for mCRC patients with irinotecan-refractory and oxaliplatin-na€ ıve tumors harboring wild-type KRAS. Oxaliplatin-containing chemotherapy resulted in equivalent PFS both as a second-line and a third-line therapy, enabling delay of the administration of FOLFOX and CapeOX until subsequent treatment cycles. (Cancer Sci 2013; 104: 473-480) A t present, a limited number of active drugs are available for the treatment of metastatic colorectal cancer (mCRC), and the upfront doublet combination of fluoropyrimidines plus either oxaliplatin or irinotecan is regarded as the reference strategy for patients for whom intensive therapy is appropriate.(1-3) Before the era of targeted agents, treatment strategies in terms of the combination or sequence of cytotoxic agents were rather simple; survival outcomes did not differ according to either the administration sequence of oxaliplatin or irinotecan, and whether sequential or combination chemotherapy was applied in the treatment continuum was inconsequential.(4-7) Treatment strategies have become more complicated in the era of targeted agents.Bevacizumab plus chemotherapy as initial chemotherapy improved efficacy without significant adverse events and was proven effective as second-line continuation beyond progression; (8)(9)(10)(11)(12) however, limited overall survival (OS) benefit was observed when bevacizumab was combined with optimal doublet chemotherapy.As a first-line treatment, cetuximab has shown OS benefit when combined with irinotecan plus infusional 5-fluorouracil...

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Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Second‐line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild‐type KRAS

et al. 2013

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“…In the contemporary management of patients with synchronous hepatic colorectal metastases, a growing body of literature supports a multimodality approach whereby patients undergo resection of primary and metastatic sites, systemic therapy, and, in selected patients, radiotherapy. 9,10,[22][23][24][25][26][27] The appropriate timing of the various interventions is a topic of significant debate. The classical therapeutical pathway to this disease foresees patients first undergoing the primary tumor resection (in rectal patients following chemoradiation) followed by systemic therapy of an arbitrary duration, typically 6 months or longer.…”

Section: Discussionmentioning

confidence: 99%

Is There a Role for Simultaneous Hepatic and Colorectal Resections? A Contemporary View from NSQIP

Worni

Mantyh

Akushevich

et al. 2012

Journal of Gastrointestinal Surgery

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Introduction The optimal timing of primary and metastatic tumor management in patients with synchronous hepatic colorectal metastases remains controversial. We aimed to compare perioperative outcomes of simultaneous colorectal/liver resection (SCLR) with isolated resections utilizing a national clinical database. Methods NSQIP data from 2005 to 2009 were examined to construct risk-adjusted generalized linear models and to calculate group-specific predicted estimates. These were used to compare 30-day perioperative outcomes among patients undergoing SCLR with colorectal (CR) and liver resections (LR) only in patients with metastatic colorectal cancer. Results A total of 3,983 patients were identified, who underwent SCLR (192), LR (1,857), or CR (1,934). Rectal resection was performed in 45 (23.4 %) SCLR patients and 269 (13.9 %) CR patients (p<0.001). Major hepatectomy was performed in 69 (35.9 %) SCLR patients and 774 (41.7 %) LR patients (p00.12). Median adjusted operation time (SCLR: 273 min, 95 % CI: 253-295; CR: 172, CI: 168-177; LR: 222, CI: 217-228; p<0.001) and median adjusted length of hospital stay (SCLR: 9.5 days, CI: 8.8-10.4; CR: 8.1, CI: 7.9-8.3; LR: 6.4, CI: 6.3-6.6; p<0.001) were longer for SCLR compared to CR and LR. Adjusted predicted risks for at least one postoperative complication were higher in SCLR (36.3 %) than in CR (26.6 %) and LR (19.8 %) (p<0.003), mostly due to infectious/ cardiopulmonary issues. Discussion In SCLR patients, the risk of 30-day adverse outcomes is higher, and median operation time as well as length of hospital stay is longer compared to CR and LR patients. However, the expected combined morbidities of staged procedures though likely favor SCLR in carefully selected patients undergoing even complex hepatic and colorectal resections and should be considered.

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“…Five studies were excluded because they involved Ͻ50 patients treated with EGFRIs [96 -100]. Six studies were excluded because they did not refer to the frequency of folliculitis [101][102][103][104][105][106]. Overall, 50 publications were initially selected and are summarized in Table 2 [2-7, 9 -16, 20, 27, 107-140].…”

Section: Articles Selectedmentioning

confidence: 99%

Folliculitis Induced by EGFR Inhibitors, Preventive and Curative Efficacy of Tetracyclines in the Management and Incidence Rates According to the Type of EGFR Inhibitor Administered: A Systematic Literature Review

et al. 2012

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Introduction. Folliculitis is the most common side effect of epidermal growth factor receptor (EGFR) inhibitors (EGFRIs). It is often apparent, altering patients' quality of life and possibly impacting compliance. Variations in terms of the treatment‐related incidence and intensity have not been fully elucidated. Tetracyclines have been recommended for the prophylaxis and treatment of folliculitis but their efficacy is yet to be established. Materials and Methods. We carried out two systematic literature reviews. The first assessed the preventive and curative efficacy of tetracyclines. The second assessed the incidence of grade 3–4 folliculitis in the main clinical studies published. Results. In four randomized studies, preventive tetracycline treatment was associated with a significantly lower incidence of grade 2–3 folliculitis and a better quality of life in three of the four studies. In curative terms, tetracycline efficacy was not evaluated in any randomized study, but an improvement in grade ≥2 folliculitis was reported in case series. The frequency and severity of folliculitis seem to be greater with the antibodies than with the tyrosine kinase inhibitors. Analysis restricted to lung cancer studies showed a statistically greater incidence in terms of grade 3–4 folliculitis with cetuximab (9%) and erlotinib (8%) than with gefitinib (2%) (p < .0001). Conclusion. Unless contraindicated, a tetracycline should be routinely prescribed prophylactically for patients treated with an EGFRI (level of evidence, B2). In curative therapy, the level of evidence for tetracycline efficacy is low (level of evidence, D). The incidence of grade 3–4 folliculitis induced by EGFRIs appears to be lower with gefitinib.

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Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer

Abstract: Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.

Cited by 906 publications

References 24 publications

Second‐line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild‐type KRAS

Second‐line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild‐type KRAS

Is There a Role for Simultaneous Hepatic and Colorectal Resections? A Contemporary View from NSQIP

Folliculitis Induced by EGFR Inhibitors, Preventive and Curative Efficacy of Tetracyclines in the Management and Incidence Rates According to the Type of EGFR Inhibitor Administered: A Systematic Literature Review

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