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Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti‐epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta‐analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty‐four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta‐analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left‐sided tumors, 41.3% among right‐sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left‐sided tumors, 46.3% among right‐sided tumors; P, A systematic literature review and meta‐analysis were conducted to estimate the prevalence of RAS and BRAF mutations by tumor sidedness in metastatic colorectal cancer (mCRC) patients. RAS, KRAS, and BRAF mutations were found to vary significantly by tumor location, occurring more frequently among right‐sided colon tumors than left‐sided colon tumors. These results inform clinicians and researchers regarding the mCRC patient population and potential targeted patients for anti‐EGFR therapies.

Aim: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Materials & methods: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. Results: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8–48.5%); ranging from 33.7% (95% CI: 28.4–39.3%) to 54.1% (95% CI: 51.7–56.5%) between sources. Conclusion: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

Introduction This study aimed to describe medical oncologist’s opinions and perceptions regarding the management of dermatologic toxicities among metastatic colorectal cancer (mCRC) patients who were treated with panitumumab in the USA and assess if there were differences across demographic and clinical characteristics. Methods We developed a survey based on the current literature and expert opinions regarding the management of dermatologic toxicities. The survey was implemented online in September 2016. Eligible oncologists were board certified and had treated at least five new or continuing patients with mCRC in the last 3 months, among whom at least three patients had received or were currently receiving panitumumab. Results A total of 250 oncologists completed the survey. The data suggest that approximately 82% of patients received recommendations for moisturizer, 88% for sunscreen and 67% for ultraviolet (UV)-protective garments prior to or at the time of initiation of panitumumab therapy. There were minor differences in how dermatologic toxicities were managed across specific demographic or clinical groups. The data also suggest that the management associated with panitumumab use among mCRC patients can be greatly improved. Conclusions Our results highlight the urgent need for heightened education regarding dermatologic toxicity management among oncologists who treated mCRC patients with panitumumab. Easily implemented strategies, such as moisturizer, sunscreen, and UV-protective garments should be recommended to all patients. Funding Amgen, Inc. Plain Language Summary Plain language summary available for this article.

681 Background: There is evidence to suggest that tumor biology and pathology differ for right- and left-sided colon tumors which may affect treatment efficacy and clinical outcomes. Therefore, we conducted a systematic review and meta-analysis of the available scientific literature to summarize the prevalence of RAS and BRAF mutations by primary tumor location and to identify potential sources of heterogeneity in mutation prevalence. Methods: This study was conducted in accordance with PRISMA guidelines. Using comprehensive search strings, several medical research databases were queried and relevant variables abstracted including tumor mutation prevalence, study country, metastasis site, tissue source, study design, study dates, median age of the cohort, mutation assessment method, and length of follow-up. Results: Final abstraction was performed on 40 articles, 36 observational studies and 4 randomized trials. Most studies were from Europe (n = 16), followed by Asia (n = 11), USA, (n = 7), Australia (n = 3), and the remaining 3 were conducted in multiple countries. The proportion of males in each study ranged from 37% to 72%, and the mean age ranged from 55 to 76 years. The prevalence of all RAS mutations was significantly higher among right-sided colon tumors than left-sided colon tumors (44%, 95% Confidence Interval [CI]: 38 – 50% vs 34%, 95% CI: 29 – 38%; p = 0.009). BRAF mutation prevalence was also higher in right-sided tumors (16.1%, 95% CI: 13.1 – 19.6% vs 4.4%, 95% CI: 3.4 – 5.8%; p < 0.0001). Conclusions: This systematic review and meta-analysis found that mutation prevalence varied by primary tumor right- or left-sided location among mCRC patients. Some of this variation may be explained by study characteristics such as mutation assessment method, country and length of follow-up. Further research will help to better understand treatment and outcome implications of tumor sidedness and mutation prevalence.

639 Background: Dermatologic toxicity can be a limiting factor for the use of anti-EGFR therapy such as panitumumab. There is a paucity of real world data regarding the management of dermatologic toxicity among metastatic colorectal cancer (mCRC) patients treated with panitumumab in the United States (U.S.). The objective of this study is to describe oncologist's opinions regarding timing of skin rash management in relation to the initiation of treatment and perceptions regarding rash management strategies. Methods: A total of 125 oncologists were recruited from a national database via a third independent party. Eligible oncologists (i.e.: licensed and practicing oncologist who had treated at least three new or continuing mCRC patients with panitumumab in the last year) completed an online survey to report their opinions regarding the grade and type of dermatologic toxicities seen and their perceptions about management strategies for mCRC patients who are treated with panitumumab. The timing of rash management initiation was defined as pre-emptive (prior to the appearance of the rash) or reactive (after any signs of skin rash). Results: Based upon their collective experience, oncologists expect that 44% of patients will develop acneiform rash while on treatment. More than half (58%) of the oncologists reported they did not follow any practice guidelines regarding the management of dermatologic toxicities. The oncologists reported that they pre-emptively initiated the management of dermatologic toxicities in 53% of their patients. Skin moisturizer and sunscreen were reported to be the most critical preemptive management approach, while skin moisturizer, over-the-counter topical steroids, and oral antibiotics were reported to be the most critical reactive management tools for Grades 1, 2, and 3, respectively. Conclusions: Despite evidence from randomized controlled trials, a majority of oncologists do not follow guidelines for dermatologic management of EGFR-I rash. There is a clear need for better physician education and awareness of mitigation strategies for skin toxicity management in mCRC patients treated with panitumumab.

638 Background: Our objective was to use real world data to evaluate of the treatment continuum of bevacizumab (Bmab), cetuximab (Cmab), panitumumab (Pmab) or no biologics across 1st, 2nd, and 3rd lines among metastatic colorectal cancer (mCRC) patients who were treated at community cancer centers in the United States. This objective was applied separately to patients with confirmed KRAS, NRAS, or BRAF wild-type (WT) or mutation (MUT) status, as well as patient who did not receive biomarker testing (UNK). Methods: This descriptive study utilized data from the Oncology Services Comprehensive Electronic Records (OSCER) database. It included 5,446 (2,064 WT, 1,807 MUT, and 1,575 UNK) patients diagnosed with mCRC between 1/1/2011 and 8/31/2015. Patients were stratified into the following mutually-exclusive categories in 1st, 2nd line, and 3rd line: Pmab only, Cmab only, Bmab only, or no biologic. Patients who survived and continued therapy were followed through the lines of therapy. Results: 23.8% of WT, 36.3% of MUT and 49.5% of UNK patients did not receive a biologic in 1st line. There were 1,003 WT patients who were treated with Bmab in 1st. Of those, n=587 (58.5%) survived and elected to continue treatment in 2nd line as follows: n=221 (37.6%) continued with Bmab, n=216 (36.8%) initiated Cmab, n=65 (11.1%) initiated Pmab, and n=85 (14.5%) received no biologic in 2nd line. Of the 221 WT patients who received Bmab in 1st and 2nd line, n=129 (58.4%) survived and initiated 3rd line treatment, of which n=20 (15.5%) received Bmab in 3rd line. There were 127/2,604 (4.9%) WT patients who were treated with Pmab in 1st line. Of those 127 patients, n=46 (36.2%) survived and elected to continue treatment in 2nd line as follows: n=11 (29.3%) continued treatment with Pmab in 2nd line, while n=14 (30.4%) initiated treatment with Bmab, n=4 (8.7%) initiated treatment with Cmab, and n=16 (36.4%) did not receive a biologic in 2nd line. Conclusions: A small proportion of patients continued treatment with the same biologic throughout subsequent lines of therapy. Many patients were not treated with a biologic in any line, even if they were confirmed WT.

663 Background: There is limited observational data on the use of RAS test results and treatment patterns with chemotherapy and biologics among metastatic colorectal cancer (mCRC) patients. Our objective was to use real world data to evaluate the treatment sequences of mCRC patients who have wild-type RAS (KRAS, NRAS), or BRAF and who are treated at community cancer clinics within the United States (U.S.). Methods: The sample included 536 patients in the Oncology Services Comprehensive Electronic Records (OSCER) database who were diagnosed with mCRC between 1/1/2011 and 8/31/2015. All patients had available treatment data and were confirmed to have wild-type RAS or BRAF. Patients were stratified into mutually-exclusive categories based on 1st line treatment with chemotherapy in combination with either bevacizumab (Bmab), cetuximab (Cmab), panitumumab (Pmab), a combination of Pmab, Cmab or Bmab, or no biologics. Descriptive statistics were used to summarize the data. Results: The demographics of the sample were as follows: mean age 67 years (standard deviation = 12), 55% male, 70% White, and 50% with ECOG value of zero. The use of Bmab, Cmab, or Pmab in combination with chemotherapy in 1st line treatment was follows: Bmab only (n = 270, 50%), Cmab only (n = 81, 15%), Pmab only (n = 28, 5%), and a combination of either Bmab, Cmab and/or Pmab (n = 6, 1%). No biologics were administered to 151 (28%) of the sample in 1st line. There were no statistically significant differences in age, gender, race, insurance type, region of the U.S. or ECOG status at mCRC diagnosis across the 1st line treatment categories. Of the 385 patients who received a biologic in 1st line, 94 (24%) of those who survived and selected to continue treatment received a biologic in 2nd line. Of these 94 patients, 25 (27%) of those who survived and selected to continue treatment also received a biologic in 3rd line. Conclusions: Bmab was the most commonly-used biologic among mCRC patients with wild-type RAS or BRAF in this descriptive study. Future research is needed to better understand what factors impact treatment decisions among mCRC patients.

598 Background: Anti-EGFR therapies are recommended for metastatic colorectal cancer (mCRC) patients with confirmed wild-type RAS (exons 2, 3, 4 of KRAS and NRAS) status. There is limited published information on the prevalence of RAS mutations using real world data. The objective of this study was estimate the prevalence of RAS and BRAF mutations among patients with mCRC in the Middle East and Northern Africa (MENA) in an effort to inform the rationale for biomarker testing and treatment choice. Methods: The study included 1,669 patients from August 2013 to July 2015 with mCRC from Algeria, Bahrain, Egypt, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Qatar, Saudi Arabia, and the United Arab Emeritus. Information on RAS mutation status was obtained from one pathology lab using High Resolution Melting Analysis. Extended RAS analysis was conducted in a subset of patients, including: overall RAS (exon 2, 3, 4 of KRAS and NRAS; n = 750), KRAS exon 2 (n = 750), KRAS exon 3 and 4 (n = 507), NRAS exon 2, 3, and 4 (n = 507), and BRAF exon 15 (n = 78). The proportion of patients with each mutation was summarized. Results: The overall RAS mutation in the full sample was 35.3% (n = 589/1669). The observed mutation for KRAS exon 2 in a subset of patients with extended RAS analysis (n = 750) was 32.4% (243/750). Out of the subjects with wild-type exon 2 (n = 507), the observed mutations rates were as follows: KRAS exon 4 (20/507 = 3.9%), KRAS exon 3 (13/507 = 2.6%), NRAS exon 2 (7/507 = 1.4%), NRAS exon 3 (6/507 = 1.2%), and NRAS exon 4 (0%). The prevalence of BRAF exon 15 was 3.8% (3/78). The most robust data on specific RAS mutations was obtained from Algeria, Egypt, and Saudi Arabia. The prevalence of KRAS exon 2 mutations in these countries was as follows: Algeria (n = 33/86 = 38.4%), Egypt (n = 83/303 = 27.4%), Saudi Arabia (n = 85/245 = 34.7%). Conclusions: To our knowledge, this is the first study to evaluate the prevalence of RAS and BRAF mutations in the Middle East using real world data. The results of this descriptive study illustrate that there is variation in the prevalence of RAS and BRAF mutations in MENA.