Association of progression‐free survival, overall survival, and patient‐reported outcomes by skin toxicity and <i>KRAS</i> status in patients receiving panitumumab monotherapy

Peeters, Marc; Siena, Salvatore; Cutsem, Éric Van; Sobrero, Alberto; Hendlisz, Alain; Cascinu, Stefano; Kalofonos, Haralabos P.; Devercelli, Giovanna; Wolf, Michael; Amado, R. G.

doi:10.1002/cncr.24088

Cited by 123 publications

(86 citation statements)

References 28 publications

(55 reference statements)

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“…For both cetuximab (2) and panitumumab (35), a correlation between skin toxicity and survival was reported. In the present study, such a relationship was observed but it did not reach statistical significance (P ¼ 0.077).…”

Section: Discussionmentioning

confidence: 99%

Cetuximab Pharmacokinetics Influences Progression-Free Survival of Metastatic Colorectal Cancer Patients

Azzopardi

Lecomte²,

Ternant³

et al. 2011

Clinical Cancer Research

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Purpose: An ancillary phase II study was conducted to study interindividual variability in cetuximab pharmacokinetics and its influence on progression-free survival (PFS) in metastatic colorectal cancer patients cotreated with irinotecan and 5-fluorouracil.Experimental Design: Ninety-six patients received cetuximab as an infusion loading dose of 400 mg/m 2 followed by weekly infusions of 250 mg/m 2 . Doses of irinotecan and 5-fluorouracil were adjusted individually. Cetuximab concentrations were measured by ELISA. Compartmental pharmacokinetic parameters were estimated by a population approach, and PFS was analyzed using a Cox model. Results: Cetuximab pharmacokinetics was best described using a two-compartment model with both first-order and saturable (zero-order) elimination. Estimated pharmacokinetic parameters (% standard error) were as follows:, and zero-order elimination rate k 0 ¼ 8.71 mg/d (10%). Body surface area influenced V 1 , V 2 , and k 0 . Pretreatment serum albumin influenced CL. Risk of disease progression decreased with cetuximab global clearance (cumulative dose/cumulative area under the concentration versus time curve; P ¼ 0.00016). Median PFS of patients with a cetuximab residual concentration on day 14 below median value was 3.3 months as compared with 7.8 months for the other patients (P ¼ 0.004).Conclusions: Cetuximab pharmacokinetics in colorectal cancer patients can be described using a model combining linear and nonlinear elimination rates. PFS is influenced by global clearance of cetuximab, a parameter that can be estimated using cetuximab residual concentration on day 14.

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Section: Discussionmentioning

confidence: 99%

Cetuximab Pharmacokinetics Influences Progression-Free Survival of Metastatic Colorectal Cancer Patients

Azzopardi

Lecomte²,

Ternant³

et al. 2011

Clinical Cancer Research

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“…Three studies were excluded from the analysis: one study used an egfri in both arms 13 , one did not present rash rates according to either grades 3 and 4 criteria or allgrades criteria 14 , and one study was a duplicate of another study 15 . Thus thirteen studies were eligible for inclusion in the meta-analysis ( Table ii).…”

Section: Resultsmentioning

confidence: 99%

Rash Rates with EGFR Inhibitors: Meta-Analysis

Mittmann

Seung

2011

Current Oncology

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Introduction: Currently marketed epidermal growth factor receptor inhibitors (EGFRIS) have been associated with high rates of dermatologic toxicity. Methods: We formally reviewed the literature at MEDLINE and EMBASE. Additional searches were conducted using Internet search engines. Studies were eligible if they were randomized controlled clinical trials of egfris, specifically cetuximab and panitumumab, in which at least one arm consisted of a non-egfri treatment and rash safety data were reported. The random effects method was used to pool differences in incident rash rates. Results are summarized as differences in incident rash (EGFRIS therapy rate minus the non-EGFRIS therapy rate) with corresponding 95% confidence intervals (CIS) for all severity grades of rash and for grades 3 and 4 rash. Results: Sixteen studies met the initial inclusion criteria of randomized controlled trials comparing EGFRIS with non-EGFRIS therapy. Seven publications that provided information on all severity grades of rash were found to have an overall difference in incident rash rate of 0.74 (95% CI: 0.68 to 0.81; p < 0.01). Thirteen studies that reported the incidence of grades 3 and 4 rash showed an overall difference in the incident rash rate of 0.12 (95% CI: 0.09 to 0.14; p < 0.01) between EGFRIS and non-EGFRIS therapy. Sensitivity analyses showed that the results were generally robust, but sensitive to small samples. Conclusions: Results quantify the difference in rash rates between EGFRIS and non-EGFRIS therapy.

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“…In 2010, the FOLFIRI/panitumumab combination was compared to FOLFIRI alone in second-line treatment. In the KRAS-wt patients, when panitumumab was added to FOLFIRI median PFS was 5.9 months versus 3.9 months for FOLFIRI alone (p=0.004) (Peeters et al 2009). Panitumumab, in conjunction with chemotherapy regimen, has also been evaluated in firstline therapy for mCRC.…”

Section: Panitumumab (Table 3)mentioning

confidence: 98%

Systemic Treatment in Recurrent and Metastatic Unresectable Rectal Cancer

Otte¹,

Tehfé²,

Ayoub³

et al. 2011

Rectal Cancer - A Multidisciplinary Approach to Management

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Association of progression‐free survival, overall survival, and patient‐reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy

Abstract: More severe ST, by both clinical grading and PRO, is associated with better CRC symptoms and HRQOL and with longer OS and PFS among panitumumab-treated patients. The associations for PFS were more pronounced in patients with WT KRAS tumors.

Cited by 123 publications

References 28 publications

Cetuximab Pharmacokinetics Influences Progression-Free Survival of Metastatic Colorectal Cancer Patients

Cetuximab Pharmacokinetics Influences Progression-Free Survival of Metastatic Colorectal Cancer Patients

Rash Rates with EGFR Inhibitors: Meta-Analysis

Systemic Treatment in Recurrent and Metastatic Unresectable Rectal Cancer

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