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ASCO 2017 highlights and editor recommendations - Colorectal Cancer


Editor Selected ASCO Abstracts 2017 – Colorectal Cancer

  • Circulating tumor DNA (ctDNA) utilizing a high-sensitivity panel to detect minimal residual disease post liver hepatectomy and predict disease recurrence

    Michael J. Overman, Jean-Nicolas Vauthey, Thomas A. Aloia, Claudius Conrad, Yun Shin Chun, Allan Andresson Lima Pereira, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 3522)

    Editorial comment from Dr Cremolini
    The potential interest of the quantitative and qualitative evaluation of cfDNA in liquid biopsy is a field of interest in many solid malignancies. With regard to colorectal cancer, the potential application of liquid biopsy has been mainly focused on the early identification of mechanisms of acquired resistance to anti-EGFRs, but in spite of interesting and promising proof-of-concept findings, their way toward clinical practice has been halted by the lack of high levels of evidence. These works, commented in the poster discussion session, highlight another potential application of cfDNA in colorectal cancer, focusing on its prognostic impact in locally advanced rectal cancer and in patients undergoing radical resection of their liver metastases. The detection of cfDNA after neoadjuvant chemoradiotherapy or after rectal surgery predicts relapse with high specificity, independently of the exposure to adjuvant chemotherapy and the histopathological complete response. Similarly, the detection of cfDNA after liver metastases’ surgical resection predicts both relapse free and overall survival. These findings continue and corroborate previous results achieved by Tie et al. (Sci Transl Med 2016), evidencing the ability of cfDNA in unveiling the minimal residual disease following resection of stage II colorectal cancer. A currently ongoing clinical trial in stage II resected patients (where tools able to estimate the risk of relapse are extremely needed) incorporates results of cfDNA as decision drivers to administer or not adjuvant chemotherapy.

  • The potential of circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy decision making in locally advanced rectal cancer (LARC)

    Jeanne Tie, Joshua Cohen, Yuxuan Wang, Lu Li, Isaac Kinde, Hany Elsaleh, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 3521)

    Editorial comment from Dr Cremolini
    The potential interest of the quantitative and qualitative evaluation of cfDNA in liquid biopsy is a field of interest in many solid malignancies. With regard to colorectal cancer, the potential application of liquid biopsy has been mainly focused on the early identification of mechanisms of acquired resistance to anti-EGFRs, but in spite of interesting and promising proof-of-concept findings, their way toward clinical practice has been halted by the lack of high levels of evidence. These works, commented in the poster discussion session, highlight another potential application of cfDNA in colorectal cancer, focusing on its prognostic impact in locally advanced rectal cancer and in patients undergoing radical resection of their liver metastases. The detection of cfDNA after neoadjuvant chemoradiotherapy or after rectal surgery predicts relapse with high specificity, independently of the exposure to adjuvant chemotherapy and the histopathological complete response. Similarly, the detection of cfDNA after liver metastases’ surgical resection predicts both relapse free and overall survival. These findings continue and corroborate previous results achieved by Tie et al. (Sci Transl Med 2016), evidencing the ability of cfDNA in unveiling the minimal residual disease following resection of stage II colorectal cancer. A currently ongoing clinical trial in stage II resected patients (where tools able to estimate the risk of relapse are extremely needed) incorporates results of cfDNA as decision drivers to administer or not adjuvant chemotherapy.

  • Impact of consensus molecular subtyping (CMS) on overall survival (OS) and progression free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance)

    Heinz-Josef Lenz, Fang-Shu Ou, Alan P. Venook, Howard S. Hochster, Donna Niedzwiecki, Richard M. Goldberg, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 3511)

    Editorial comment from Dr Cremolini
    The Consensus Molecular Subgroups (CMS) classification of colorectal cancer is based on the identification of different gene signatures characterizing different tumours. Authors of two recent and extremely relevant trials (FIRE-3 and CALGB80405) in the landscape of metastatic colorectal cancer investigated the prognostic and predictive impact of this classification in stage IV patients treated with a chemotherapy doublet plus bevacizumab or cetuximab. CMS1 subtype (immune, enriched in MSI-high and BRAF V600E mutants) is associated with the worse prognosis in both trials, thus confirming results in terms of survival after relapse already reported by Guinney et al. in the original series of mainly stage II and III patients. Less clear and consistent data emerge in terms of predictivity: while in FIRE-3 no differential effect of bevacizumab versus anti-EGFR is evident among CMS subtypes, in CALGB80405 CMS1 tumours seems to derive more benefit from bevacizumab than cetuximab, and CMS2 and 4 cancers seem more sensitive to EGFR than angiogenesis inhibition.

    As a major limitation, these analyses are conducted in the RAS (FIRE-3) or KRAS (CALGB80405) wild-type populations, thus not considering the potential impact of other biomarkers routinely used in the daily practice, such as BRAF V600E mutation or microsatellite instability. In spite of the obvious biologic and scientific interest of these findings, they will become relevant for clinical practice only when their added value (as compared with information provided by other easy-to-obtain markers) will be demonstrated.

  • Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial

    Sebastian Stintzing, Pratyaksha Wirapati, Heinz-Josef Lenz, Daniel Neureiter, Ludwig Fischer von Weikersthal, Thomas Decker, et al.

    J Clin Oncol 35, 2017 (suppl; abstr 3510)

    Editorial comment from Dr Cremolini
    The Consensus Molecular Subgroups (CMS) classification of colorectal cancer is based on the identification of different gene signatures characterizing different tumours. Authors of two recent and extremely relevant trials (FIRE-3 and CALGB80405) in the landscape of metastatic colorectal cancer investigated the prognostic and predictive impact of this classification in stage IV patients treated with a chemotherapy doublet plus bevacizumab or cetuximab. CMS1 subtype (immune, enriched in MSI-high and BRAF V600E mutants) is associated with the worse prognosis in both trials, thus confirming results in terms of survival after relapse already reported by Guinney et al. in the original series of mainly stage II and III patients. Less clear and consistent data emerge in terms of predictivity: while in FIRE-3 no differential effect of bevacizumab versus anti-EGFR is evident among CMS subtypes, in CALGB80405 CMS1 tumours seems to derive more benefit from bevacizumab than cetuximab, and CMS2 and 4 cancers seem more sensitive to EGFR than angiogenesis inhibition.

    As a major limitation, these analyses are conducted in the RAS (FIRE-3) or KRAS (CALGB80405) wild-type populations, thus not considering the potential impact of other biomarkers routinely used in the daily practice, such as BRAF V600E mutation or microsatellite instability. In spite of the obvious biologic and scientific interest of these findings, they will become relevant for clinical practice only when their added value (as compared with information provided by other easy-to-obtain markers) will be demonstrated.

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