Treatment choices in metastatic colorectal cancer according to sidedness and RAS/BRAF status: a national survey by the Brazilian Gastrointestinal Tumors Group (GTG)

ABSTRACT

Objectives: Tumor sidedness and RAS/BRAF status have changed the treatment landscape of metastatic colorectal cancer (mCRC). This study was performed to understand the first line choices of Brazilian oncologists for patients with mCRC, especially in the emergent context of tumor sidedness and RAS/BRAFV600E status. Methods: This was a cross-sectional electronic survey composed of six questions sent to Brazilian medical oncologists through social media. The survey instrument collected demographic data of participants and assessed current practices in terms of first-line treatment choices for fit patients with mCRC. Participants with at least 50% of their clinical practice dedicated to patients with GI malignancies were deemed GI specialists. Results: The survey was completed by 239 medical oncologists from across the country. Most oncologists were male (59%) and were in oncology practice for less than 10 years (62.2%). Only 20.9% of the participants were specialists in GI tumors. For left-sided, wild-type (wt) RAS/wt-BRAFV600E mCRC, most oncologists (82%) chose first line chemotherapy (CT) + anti-EGFR therapy, with 53.6% of them preferring FOLFIRI as the CT backbone. Meanwhile, for right-sided, wt-RAS/wt-BRAFV600E mCRC, the majority (70.7%) would offer CT + bevacizumab (53.9% with FOLFOX). For mutated-RAS mCRC, most oncologists decided for FOLFOX + bevacizumab (51.9%). Subgroup analyses revealed statistically significant differences for therapeutic choices in first line for left-sided wt-RAS/wt-BRAFV600E mCRC: female oncologists prefer FOLFOX as CT backbone ( p= 0.004) and in right-sided wt-RAS/wt-BRAFV600E mCRC, GI cancer specialists more often use FOLFOXIRI and bevacizumab (18 vs 7.9%; p= 0.001). Conclusion: Our survey indicates that tumor sidedness influences the choice of both CT backbone and monoclonal antibody in unresectable wt-RAS mCRC. In addition, oncologists' gender and percentage of time dedicated to treat GI cancers also impacted on therapeutic choices for mCRC in Brazil.

RESUMO

Objetivos: A lateralidade tumoral e o status RAS/BRAF mudaram o cenário de tratamento do câncer colorretal metastático (CCRm). Este estudo foi realizado para entender as primeiras linhas de escolha de oncologistas brasileiros para pacientes com CCRm, especialmente no contexto emergente de lateralidade tumoral e o status RAS/BRAFV600E. Métodos: Tratase de uma pesquisa eletrônica transversal, composta por seis questões encaminhadas aos médicos oncologistas brasileiros por meio das mídias sociais. O instrumento de pesquisa coletou dados demográficos dos participantes e avaliou as práticas atuais em termos de opções de tratamento de primeira linha para pacientes em tratamento com CCRm. Participantes com pelo menos 50% de sua prática clínica dedicada a pacientes com malignidades gastrointestinais foram considerados especialistas gastrointestinais (GI). Resultados: A pesquisa foi preenchida por 239 médicos oncologistas de todo o país. A maioria dos oncologistas era do sexo masculino (59%) e praticava oncologia há menos de 10 anos (62,2%). Apenas 20,9% dos participantes eram especialistas em tumores GI. Do lado esquerdo, o CCRm do tipo selvagem (wt) RAS/wt-BRAFV600E, a maioria dos oncologistas (82%) escolheu como primeira linha a quimioterapia (QT) + terapia anti-EGFR, com 53,6% deles preferindo o FOLFIRI como base da QT. Entretanto, para o CCRm do lado direto, no (wt)-RAS/wt-BRAFV600E, a maioria (70,7%) oferece QT + bevacizumabe (53,9% com FOLFOX). Para o CCRm RAS mutado, a maioria dos oncologistas decidiu pelo FOLFOX + bevacizumabe (51,9%). Análises de subgrupos revelaram diferenças estatisticamente significantes para as escolhas terapêuticas na primeira linha de tratamento do CCRm do lado esquerdo wt-RAS/ wt-BRAFV600E: oncologistas do sexo feminino preferem FOLFOX como base da QT (p=0,004), e no CCRm do lado direito, wt-RAS/wt-BRAFV600E, especialistas em câncer gastrointestinal mais frequentemente usam FOLFOXIRI e bevacizumabe (18 vs 7,9%; p=0,001). Conclusão: Nossa pesquisa indica que a lateralidade do tumor influencia em ambas a escolha base da QT e do anticorpo monoclonal no CCRm não ressecável do RAS. Além disso, os oncologistas em gênero e porcentagem de tempo dedicados ao tratamento de cânceres gastrointestinais também tiveram impacto nas escolhas terapêuticas para o CCRm no Brasil.

Keywords:

Colorectal neoplasms - Surveys and questionnaires - Antineoplastic agentes.

Descritores:

Neoplasias colorretais - Pesquisas e questionários - Antineoplásicos.

AUTHOR'S CONTRIBUTION

Renata D'Alpino Peixoto: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.

Rachel P Riechelmann: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.

Gabriel Prolla: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.

Rui F. Weschenfelder: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.

Gustavo dos Santos Fernandes: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.

Guilherme S Pereira: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing.

Maria de Lourdes de-Oliveira: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing.

Juliana F Rego: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing.

Duilio R Rocha-Filho: Collection and assembly of data, Data analysis and interpretation, Final approval of manuscript, Manuscript writing.

Anelisa K. Coutinho: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.

Publication History

Received: 20 February 2018

Accepted: 21 March 2018

Article published online:
15 April 2019

• REFERENCES

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre L, Jemal A.. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; Nov; 68 (06) 394-424 30207593 https://doi.org/10.3322/caac.21492
• Ministério da Saúde (BR). Instituto Nacional de Câncer - José Alencar Gomes da Silva (INCA). Estimativa - 2018. Incidência de Câncer no Brasil. Rio de Janeiro (RJ): INCA;; 2018. Available from: http://www1.inca.gov.br/estimativa/2018/estimativa-2018.pdf
• Benedix F, Kube R, Meyer F. et al Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum 2010; Jan; 53 (01) 57-64 20010352 https://doi.org/10.1007/DCR.0b013e3181c703a4
• Sugai T, Habano W, Jiao YF, Tsukahara M, Takeda Y, Otsuka K. et al Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis: proposal for new molecular profile of colorectal carcinomas. J Mol Diagn 2006; May; 8 (02) 193-201 https://doi.org/10.2353/jmoldx.2006.050052
• Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; Jul; 487 (7407) 330-337 22810696 https://doi.org/10.1038/nature11252
• Stintzing S, Modest DP, Rossius L. et al FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol 2016; Oct; 17 (10) 1426-1434 https://doi.org/10.1016/S1470-2045(16)30269-8
• Venook AP, Ou FS, Lenz HJ. et al Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 2017; May; 35 (Suppl 15): 3503 https://doi.org/10.1200/JCO.2017.35.15_suppl.3503
• Tejpar S, Stintzing S, Ciardiello F. et al Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol 2017; Feb; 3 (02) 194-201 https://doi.org/10.1001/jamaoncol.2016.3797
• National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Colon Cancer. Plymouth: NCCN;; 2018. Available from: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf
• Yoshino T, Arnold D, Taniguchi H. et al PanAsian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO- ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann Oncol 2018; Jan; 29 (01) 44-70 https://doi.org/10.1093/annonc/mdx738
• Scheffer MC, Cassenote AJF.. The feminization of Medicine in Brazil. Rev Bioét 2013; Aug; 21 (02) 268-277 https://doi.org/10.1590/S1983-80422013000200010
• Luft HS, Bunker JP, Enthoven AC.. Should operations be regionalized? The empirical relation between surgical volume and mortality. N Engl J Med 1979; Dec; 301 (25) 1364-1369 503167 https://doi.org/10.1056/NEJM197912203012503