Panitumumab Use in Metastatic Colorectal Cancer and Patterns of KRAS Testing: Results from a Europe-Wide Physician Survey and Medical Records Review

Trojan, Jörg; Mineur, Laurent; Tomášek, Jiří; Rouleau, Étienne; Fabián, Pavel; Maglio, Giovanna De; García‐Alfonso, Pilar; Aprile, Giuseppe; Taylor, Aliki; Kafatos, George; Downey, Gerald; Terwey, Jan-Henrik; Krieken, J. Han van

doi:10.1371/journal.pone.0140717

Cited by 10 publications

(16 citation statements)

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“…However, in a recent study of patients with mCRC evaluated for first‐line therapy, ~25% of patients did not have RAS testing requested at or at least one month after their initial diagnosis of metastatic disease (Longin, ). These findings are supported by a survey of European physicians, which revealed that RAS testing turnaround times and the unavailability of tissue were the most frequent factors cited for treating mCRC patients with unknown KRAS status (Trojan et al ., ). Moreover, a recent EQA survey found that half of all participating laboratories exceeded the required turnaround time of 14 days for RAS testing (Tack et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

et al. 2017

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An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.

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Section: Discussionmentioning

confidence: 97%

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

et al. 2017

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“…The detailed methodology of Rounds 1 and 2 (assessing KRAS only) for both the physician survey and MRR, conducted from 2012 to 2013, has been published in full previously [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…Two studies – a physician survey and a medical records review (MRR) – were initiated in Europe in 2012 to evaluate physicians’ awareness of the correct therapeutic indication for panitumumab and to establish if it was being prescribed in accordance with this indication, which is to patients with mCRC and confirmed wild-type KRAS tumour status prior to treatment with panitumumab. The studies were carried out in three consecutive rounds; the results of the first two rounds of both studies have been published previously [ 18 ]. Overall in Rounds 1 and 2 of the physician survey, 298 (99.0%) of 301 physicians responded correctly that panitumumab should be administered only to patients with confirmed KRAS wild-type tumours.…”

Section: Introductionmentioning

confidence: 99%

“…In Rounds 1 and 2 of the MRR study, 299 (97.7%) of 306 patients reportedly had confirmed wild-type KRAS status before the initiation of panitumumab treatment. Of 85 patients who were prescribed panitumumab with concurrent oxaliplatin-containing chemotherapy in Rounds 1 and 2 of the MRR, 83 (97.6%) had confirmed wild-type KRAS status before the initiation of treatment [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Panitumumab use in metastatic colorectal cancer and patterns of RAS testing: results from a Europe-wide physician survey and medical records review

et al. 2017

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BackgroundIn Europe, treatment of metastatic colorectal cancer (mCRC) with panitumumab requires prior confirmation of RAS wild-type mutation status. Two studies – a physician survey and a medical records review (MRR) – were conducted to evaluate the use of panitumumab and awareness among prescribing oncologists of the associated RAS testing requirements in clinical practice.MethodsBoth studies enrolled participants from nine European countries and were carried out in three consecutive rounds. Rounds 1 and 2 (2012–2013) examined KRAS (exon 2) testing only; the results have been published in full previously. Round 3 (2014–2015) examined full RAS testing (exons 2, 3, 4 of KRAS and NRAS) and was initiated following a change in prescribing guidelines, from requiring KRAS alone to requiring full RAS testing. For the physician survey, telephone interviews were conducted with oncologists who had prescribed panitumumab to patients with mCRC in the previous 6 months. For the MRR, oncologists were asked to provide anonymised clinical information, extracted from their patients’ records.ResultsIn Round 3, 152 oncologists and 131 patients’ records were included in the physician survey and MRR, respectively. In Round 3 of the physician survey, 95.4% (n = 145) of participants correctly identified that panitumumab should only be prescribed in RAS wild-type mCRC compared with 99.0% (n = 298) of 301 participants in Rounds 1 and 2, responding to the same question about KRAS testing. In Round 3 of the MRR, 100% (n = 131) of patients included in the study had confirmed KRAS or RAS wild-type status prior to initiation of panitumumab compared with 97.7% (n = 299) of 306 patients in Rounds 1 and 2 (KRAS only). Of those patients in Round 3, 83.2% (n = 109) had been tested for RAS status and 16.8% (n = 22) had been tested for KRAS status only.ConclusionsPhysicians’ adherence to prescribing guidelines has remained high over time in Europe, despite the change in indication for panitumumab treatment, from KRAS to RAS wild-type mCRC. Additionally, this study demonstrates the uptake of full RAS testing among the majority of oncologists and pathologists.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3740-4) contains supplementary material, which is available to authorized users.

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“…Since the publication of the 2009 ASCO guidelines, recent literature has shown increased physician awareness of the need for KRAS testing and increased testing rates [15] . However, 50% or more of eligible patients do not receive the test [ 6 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

KRAS biomarker testing disparities in colorectal cancer patients in New Mexico

Greenbaum

Wiggins

Meisner

et al. 2017

Heliyon

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IntroductionAmerican Society of Clinical Oncology (ASCO) guidelines recommend that all patients with metastatic colorectal cancer (mCRC) receive KRAS testing to guide anti-EGFR monoclonal antibody treatment. The aim of this study was to assess for disparities in KRAS testing and mutational status.MethodsThe New Mexico Tumor Registry (NMTR), a population-based cancer registry participating in the National Cancer Institute’s Surveillance, Epidemiology and End Results program, was queried to identify all incident cases of CRC diagnosed among New Mexico residents from 2010 to 2013.ResultsSix hundred thirty-seven patients were diagnosed with mCRC from 2010–2013. As expected, KRAS testing in Stage 4 patients presented the highest frequency (38.4%), though testing in stage 3 (8.5%), stage 2 (3.4%) and stage 1 (1.2%) was also observed. In those with metastatic disease, younger patients (≤ 64 years) were more likely to have had testing than patients 65 years and older (p < 0.0001). Patients residing in urban areas received KRAS testing more often than patients living in rural areas (p = 0.019). No significant racial/ethnic disparities were observed (p = 0.66). No significant differences were seen by year of testing.ConclusionAge and geographic disparities exist in the rates of KRAS testing, while sex, race/ethnicity and the year tested were not significantly associated with testing. Further study is required to assess the reasons for these disparities and continued suboptimal adherence to current ASCO KRAS testing guidelines.

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Panitumumab Use in Metastatic Colorectal Cancer and Patterns of KRAS Testing: Results from a Europe-Wide Physician Survey and Medical Records Review

Cited by 10 publications

References 30 publications

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

Panitumumab use in metastatic colorectal cancer and patterns of RAS testing: results from a Europe-wide physician survey and medical records review

KRAS biomarker testing disparities in colorectal cancer patients in New Mexico

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