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Interview with Chiara Cremolini Implications of New Data in Colon Cancer from ASCO 2017
‘Filmed by PracticeUpdate with permission for inclusion on Advances in Gastrointestinal Cancer. More information and additional ASCO coverage can be found at www.practiceupdate.com‘
Dr. Haffizulla: Welcome to this PracticeUpdate. I’m Dr. Farzanna Haffizulla. Joining me today is Dr. Chiara Cremolini, Medical Oncologist at the Tuscan Tumor Institute at the University of Pisa. So fabulous to have you here.
Dr. Cremolini: Thank you. Thank you so much for inviting me.
Dr. Haffizulla: You’re very welcome. Now, based on the results of the prospective pooled analysis of adjuvant oxaliplatin-based therapy, 3 versus 6 months, presented at this years ASCO’s plenary session, do you think we have enough evidence to shorten the duration of adjuvant therapy for patients with stage 3 colorectal cancer?
Dr. Cremolini: First of all, I think that investigators of the IDEA trial should be congratulated to arrive at the end of this very important academic effort to answer a really important question for our patients. The question is how to maximize the benefit from adjuvant treatment while minimizing the harm of adverse events, and especially in terms of neurotoxicity. However, I think that the results that have been presented are not enough today to definitely change our daily clinical practice. In other words, I think that from tomorrow on, in my clinic, I will not consider 3 months of duration of adjuvant oxaliplatin-based treatment as the standard of care for all stage 3 colorectal cancer patients.
I think that at least in those with the T4 and to the Ts, those are deemed at higher risk of relapse, I will keep them going for 6 months of adjuvant oxaliplatin-based chemotherapy. While in those at lower risk T1 to T3 and one, I will try to think about shortening the duration of treatment, or at least I will be more comfortable in interrupting the treatment after 3 months if the tolerability is not optimal.
Dr. Haffizulla: Okay. Well, thank you for that. Now, also data from the phase 2 trial investigating vitamin D supplementation in patients with metastatic colorectal cancer was released at the meeting this year, and based on these results, should clinicians be advising their patients to take vitamin D alongside chemotherapy?
Dr. Cremolini: To be honest, I think that these results are quite important also because they're on solid background in terms of evidence about the prognostic impact of vitamin D levels. Then vitamin D is good for a lot of other activities in our body, and so I think that it may be a good reason based on results of this trial to give this implementation of vitamin D, also considering that the toxicity profile is lower. I mean, there were not adverse events related to the assumption of these higher doses of vitamin D described in the trial. Clearly, this is a phase 2 trial, so the level of evidence is not that high and we would all like to see a phase 3 trial addressing the same question, but I think that the evidence provided by this trial is quite good enough to suggest to patients, in particular those with the low levels with the deficiency of vitamin D to assume these kind of supplementation in their diet. Okay.
Dr. Haffizulla: Excellent, so no additional harm. That’s excellent and...
Dr. Cremolini: No additional harm. I think this one of the most important things among the results of this trial.
Dr. Haffizulla: Absolutely. Without a doubt. Now, also data from SWOG S1406, the phase 2 trial investigating the triplet of vemurafenib, irinotecan, and cetuximab in patients with metastatic BRAF V600-mutated colorectal cancer. I know it’s being presented at this year's ASCO. How might this treatment combination fit into the treatment sequence for this subpopulation?
Dr. Cremolini: BRAF mutant metastatic colorectal cancer is a disease at very, very poor prognoses, and we definitely need new treatment options for these patients. Up to date, the triplet of chemotherapy agents in the FOLFOX serial regimen combined with bevacizumab provided the best results in terms of disease control and the survival. Clearly, this regimen, it is a more intensive one, cannot be prescribed to all BRAF mutant metastatic colorectal cancer patients because we need to fit the patients, and however, also in fit patients, this regimen does not solve the problem of such an aggressive disease. So targeted treatments, targeting BRAF V600 androgen-mutated protein could be the solution for this kind of problem, and so I think that this kind of trial is very, very important. You know, to overcome not optimal results achieved with the only BRAF inhibition strategy. I mean, vemurafenib alone does not work in metastatic colorectal cancer.
Here, I think, that the results clearly show at least two things. The first one is that the cetuximab plus irinotecan is not a good combination for BRAF mutant patients because in the control arm we had two very poor results in terms of both response rate and progression-free survival, only 2 months of median progression-free survival, this means that these patients do not derive any benefit from this kind of combination. On the other side, the addition of vemurafenib, so the double inhibition of BRAF and EGFR with a cytotoxic agent irinotecan provides better results. Clearly, we need more mature data, probably this trial will not provide us with informative data in terms of overall survival because there was a high percentage of a cross-over between arms, so the results in terms of overall survival will not be conclusive, but I think that this is the good direction to move on.
Combination of targeted agents, the triplet with irinotecan, but also the triplet of biologic agents anti-BRAF and EGFR and anti-MEK, probably this combination will provide the best results, without forgetting that at least one-third of BRAF mutant patients also have microsatellite instability. So for these patients, an immunotherapy approach of the checkpoint inhibitors might be really a good choice, so don’t forget to assess MSI status in BRAF mutant patients because these markers are often combined.
Dr. Haffizulla: Such a great point, and we want to thank you very much for the excellent work that you’re continuing to do, and for joining us here at ASCO 2017 and PracticeUpdate.
Dr. Cremolini: Thank you. Thank you so much.
Dr. Haffizulla: We hope to have you back again at some point.
Dr. Cremolini: Thank you.
Dr. Haffizulla: And to our viewers, thank you very much for joining us for this PracticeUpdate. I’m Dr. Farzanna Haffizulla. Please join us again soon.