How is KRAS testing associated with treatment and supportive care for patients with metastatic colorectal cancer? VA national assist project.

64 Background: EGFR monoclonal antibody (mAb) therapies improve quality of life and outcomes for metastatic colorectal cancer (mCRC), but only wild-type KRAS benefit from treatment. We evaluated KRAS testing and pharmacogenetic-guided treatment and supportive and end of life (EOL) care. Methods: Among a national random sample of 265 veterans diagnosed with mCRC in 2008 we evaluated KRAS testing, EGFR mAb therapy, supportive care using the Cancer Quality ASSIST indicators, and healthcare use. Three oncology nurses abstracted charts for care received 2008-2011. We linked chart to VA and Medicare administrative data and compared care received by KRAS testing and results. Results: 227/265 (85%) veterans died within 3 years and received an average of 48% of recommended supportive care processes. 96 / 265 (36%) underwent KRAS testing, of whom 41, 42, and 13 had wild-type, mutant, and indeterminant/unknown KRAS. 27/41 (66%) wild-type KRAS patients received an EGFR mAb; 18/45 (40%) patients receiving an EGFR mAb had mutant, indeterminant/unknown, or untested KRAS. KRAS testing was associated with increased systemic therapy but not differences in supportive care or intensity of care at the EOL. KRAS tested vs. not tested received hospice or palliative care (67 vs. 73%, p=0.55); any systemic therapy (96 vs. 40%, p<0.001) including new regimen in last month (0 vs. 6%); any chemotherapy in last 14 days of life (9 vs. 7%); and any acute care in last month of life (28 vs. 32%, p=0.78). Conclusions: KRAS testing was not performed for most veterans with mCRC in 2008, and EGFR mAb therapy was administered to many without wild-type KRAS. KRAS-tested patients were more likely to receive systemic treatments, and testing was not associated with greater intensity or inappropriate EOL care, and rates of such care were low among veterans.

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Clinicopathological features, efficacy of anti-EGFR therapy, and survival outcomes in patients with BRAF non-V600 mutated metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.659 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 659-659 ◽

Cited By ~ 1

Author(s):

Daisuke Kotani ◽

Sebastián Mondaca ◽

Aparna Parikh ◽

Hideaki Bando ◽

Emily Van Seventer ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Objective Response ◽

Therapy Response ◽

Clinicopathological Features ◽

Survival Outcomes ◽

Wild Type ◽

Braf Mutations ◽

Type Mutant ◽

Negative Predictive Factor

659 Background: BRAF non-V600 mutations occur in 2-3% of colorectal cancer. These mutants can be classified as RAS independent (class 2) or RAS dependent (class 3). We reported BRAF non-V600 mutations could be a negative predictive factor for anti-EGFR therapy in patients (pts) with pretreated metastatic colorectal cancer (mCRC), while mCRC pts with class 3 BRAF mutations could respond to anti-EGFR therapy because of its dependency on receptors and RAS. Methods: This study evaluates the efficacy to anti-EGFR therapy in a large cohort of pts with BRAF non-V600 mutated mCRC. Pts with mCRC referred to the participating centers from 2010 to 2017 were included. Clinicopathological features, efficacy of anti-EGFR therapy, and survival outcomes were stratified by BRAF mutational class. Results: One hundred seventeen pts with BRAF non-V600 mutated mCRC were identified. Median age was 58 years (range, 27-83), 68 pts (58%) were male, and 38 pts (33%) had right-sided tumors. Mucinous histology was seen in 11 cases (9%); concurrent RAS mutations occurred in 31 cases (27%), and 3 cases (3%) were MSI-H. Also, TP53 mutations were detected in 74 pts among 90 analyzed cases (82%). Regarding BRAF mutation subtype, 25/63/29 pts were classified as class 2/3/not reported (NR), respectively. Median OS in RAS wild-type/mutant were 44.8/34.6 months, respectively (p=0.082). The median OS in RAS wild-type pts with BRAF non-V600 mutations for class 2, 3, and NR were 25.7, 44.2, and 79.1 months, respectively (class 2 vs. 3, p=0.219). Among 40 pts treated with anti-EGFR therapy, response rates were 14%, 44%, and 40% for class 2, 3, and NR, respectively. Median PFS was 4.4, 8.3, 4.0 months for class 2, 3, and NR, respectively. Moreover, in 25 pts receiving anti-EGFR therapy as third or later line, response rate was 0%, 27%, and 50% in class 2, 3, and NR, and median PFS was 2.8, 3.7, and 4.0 months (p=0.762), respectively. Conclusions: Pts with class 2 BRAF mutations tend to have a poor prognosis compared to those with class 3 mutations. While almost half of pts with class 3 BRAF mutations responded to anti-EGFR therapy, response was rare for pts with class 2 BRAF mutations, and none achieved objective response in the third or later line.

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