Curr. Treat. Options in Oncol. (2017) 18:63 DOI 10.1007/s11864-017-0505-x
Letter to the Editor
Reply to the Letter by S. Sorscher Regarding “Implications of BRAF Mutations in dMMR Colorectal Cancers” R. Cohen, MD T. Andre´, MD* Address * Department of medical oncology, Hôpital Saint-Antoine, AP-HP, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France Email:
[email protected]
* Springer Science+Business Media, LLC 2017
This reply refers to the comment available at https://doi.org/10.1007/ s11864-017-0493-x
We thank Dr. Sorscher for his comments about our review and furthering the discussion about immune checkpoint blockade for BRAF-mutated metastatic colorectal cancers (mCRCs) harboring mismatch repair deficiency (dMMR). We agree that the evidence at this time is poor concerning the efficacy of immune checkpoint inhibitors (ICI) on patients (pts) with BRAF-mutated dMMR mCRCs. However, there is no proof that BRAF mutation may confer resistance to ICI among dMMR mCRCs. In fact, preliminary analysis recently presented with nivolumab alone at the 2017 Gastro-Intestinal Cancers Symposium showed an objective response rate of 25% on 12 BRAF-mutated cases among 74 pts with dMMR mCRC. These results are very encouraging given the poor prognosis conferred by BRAF mutation among mCRC pts [1, 2]. Considering the research paper cited by Dr. Sorscher [3], we do not think that the association between PD-L1 expression and BRAF mutation may be a robust argument in favor of immune checkpoint blockade for pts with BRAFmutated mCRC with no concern on MMR status. This association was not confirmed in multivariate analysis, probably because of the tight relation between BRAF mutation and dMMR [2]. Although PD-L1 is one of the most attractive potential biomarkers given its predictive value among pts treated for melanoma or lung cancer [4], preliminary analysis did not find any predictive value of PD-L1 for ICI efficacy among dMMR CRCs [1, 5].
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We do believe that further research will have to focus on the clinical and molecular determinants for the efficacy of ICI among dMMR mCRCs, such as PD-L1, BRAF mutation, or others. Waiting for these analyses, patients with BRAF-mutated mCRC should be proposed for clinical trial enrollment with immune checkpoint inhibitors.
References and Recommended Reading 1.
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Overman MJ, Lonardi S, Leone F, McDermott RS, Morse MA, Wong KYM, et al. Nivolumab in patients with DNA mismatch repair deficient/microsatellite instability high metastatic colorectal cancer: update from CheckMate 142. J Clin Oncol. 2017 [cited 2017 Jan 24];35. Available from: http://meetinglibrary.asco. org/content/176629-195 Venderbosch S, Nagtegaal ID, Maughan TS, Smith CG, Cheadle JP, Fisher D, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res. 2014;20:5322–30. Rosenbaum MW, Bledsoe JR, Morales-Oyarvide V, Huynh TG, Mino-Kenudson M. PD-L1 expression in
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colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. Mod Pathol. 2016;29:1104–12. Kluger HM, Zito CR, Turcu G, Baine M, Zhang H, Adeniran A, et al. PD-L1 studies across tumor types, its differential expression and predictive value in patients treated with immune checkpoint inhibitors. Clin. Cancer Res. 2017;clincanres.3146.2016. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. Programmed death-1 blockade in mismatch repair deficient colorectal cancer. J Clin Oncol. 2016;34:suppl; abstr 103.
