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ASCO 2017 highlights and editor recommendations - Colorectal Cancer – Part 3
Professor Michel Ducreux makes a selection of his recommended abstracts in colorectal cancer from ASCO 2017. Prof Ducreux gives insight on the latest significant clinical trial data including: FOXFIRE (5-Fluorouracil, OXaliplatin and Folinic acid +/- Interventional Radio-Embolisation), FRESCO (Fruquintinib Efficacy) and the IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration. View the abstracts and further editorial insight here:
Overall survival analysis of the FOXFIRE prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer
Ricky A. Sharma, Harpreet Singh Wasan, Guy A. Van Hazel, Volker Heinemann, Navesh K. Sharma, Julien Taieb, et al.09/22/2017 - 10:52J Clin Oncol 35, 2017 (suppl; abstr 3507)
Editorial comment from Prof Ducreux:
This large trial has included more than 1100 patients to evaluate the impact on survival of a combination of systemic treatment using oxaliplatin based regimen with a local treatment of the liver metastases using yttrium-resin microspheres. This is the largest trial evaluating this kind of strategy. As previously reported, even if a local active treatment is able to control the liver disease (better response rate, better liver progression-free survival), this advantage did not convert in a prolonged overall survival. This result remains difficult to understand because it has always been considered that in patients with limited liver disease, a prolonged local control could prevent the death of the patients. It has to be imagined that extra-hepatic disease is responsible of death in these patients. It may also be considered that the administration of yttrium-resin microspheres could decrease the tolerance of further systemic patients. This is disappointing regarding the cost of this kind of procedure and all the attempts that have been made to control liver diseases in the subgroup of patients with liver limited disease (Intra-arterial hepatic chemotherapy, irinotecan loaded DC-Beads, and now yttrium-resin microspheres. Furthermore, similar negative results have been observed in trials comparing these yttrium-resin microspheres versus sorafenib in hepatocellular carcinoma. It seems to suggest that the control of the liver disease is clearly not the main problem of these patients.
A randomized, double-blind, placebo-controlled, multi-centered phase 3 trial comparing fruquintinib versus placebo plus best supportive care in Chinese patients with metastatic colorectal cancer (FRESCO)
Jin Li, Shukui Qin, Yuxian Bai, Yanhong Deng, Lei Yang, Rui-hua Xu, et al.09/22/2017 - 10:44J Clin Oncol 35, 2017 (suppl; abstr 3508)
Editorial comment from Prof Ducreux:
The data presented here are very interesting mimicking with a new compound the data already obtained with two drugs: regorafenib and trifluridine/tipiracil. Fruquintinib is an oral kinase inhibitor selectively targeting vascular endothelial growth factor receptors, thus this drug should be considered as quite similar to regorafenib even if it does not work on the same targets… The hazard ratio observed in this study was even better than the one observed in the CORRECT study evaluating the role of regorafenib in refractory metastatic colorectal cancer (0.77, median survival: 6.4 versus 5.0 months)). However, it was less favorable that the hazard ratio observed in the Concur trial evaluating regorafenib versus placebo in Asian population (0.55, median survival: 8.8 versus 6.3 months), with a better effect in patients who did not receive targeted therapies before administration of regorafenib. Trifluridine/tipiracil is a completely different agent, combining a cytototoxic drug and a molecule inhibiting the degradation of this drug. In a very similar population of refractory metastatic patients, this compound showed an efficacy in terms of overall survival with a hazard ratio of 0.68, (median overall survival: 7.1 versus 5.3 months in the placebo group). The toxicity profile of this agent is neutropenia, contrasting with the toxicity of the tyrosine kinase inhibitors. Thus we will have in the future more and more compounds to treat the patients with late stage refractory metastatic colorectal cancer. However nobody knows if patients who have received and failed to regorafenib could be treated with fruquintinib. As it has been reported in the Concur trial it is clearly possible that resistance to any drug targeting angiogenesis have been developed during the first treatment with an agent of this therapeutic class. The competition could thus be imagined more between fruquintinib and regorafenib than with trifluridine/tipiracil… Finally, the availability of a Chinese drug on the occidental market is clearly not guaranteed.
Final DFS results of the SCOT study: An international phase III randomised (1:1) non-inferiority trial comparing 3 versus 6 months of oxaliplatin based adjuvant chemotherapy for colorectal cancer
Timothy Iveson, Rachel Kerr, Mark P. Saunders, Niels Henrik Hollander, Josep Tabernero, Andrew Mark Haydon, et al.09/22/2017 - 10:34J Clin Oncol 35, 2017 (suppl; abstr 3502)
Editorial comment from Prof Ducreux:
The aim of the IDEA initiative was to try to reduce the time of adjuvant chemotherapy after resection of a localized colon cancer. A consortium was created when it was considered that 6 countries were trying to launch or had already launched a trial raising this issue. These trials have some slight differences but their design was very common allowing putting together 12,834 patients to evaluate the ideal length of adjuvant chemotherapy of colon cancer.Despite this large number of patients, the results of the global analysis were not as clear as it was anticipated: the non-inferiority boundary was not reached for the global population of patients, however it was reached for Xelox (and not for Folfox), as it was reached too for T1-3 N1 tumors. These results could allow drawing the conclusion that Xelox 3 month is the best adjuvant treatment for these patients and that only pT4 and/or N2 patients should receive 6 months of treatment. No difference between 6 and 3 months of treatment was reported in the Scottish trial including 6088 patients. On the other hand, the Italian trial did not confirm the non-inferiority of 3 months of Xelox or Folfox versus 6 months of treatment. Curiously this trial that included 3759 (two thirds of stage III, one third of stage II disease), showed rather worse results with 3 months of treatment in stage II patients. This result contradicts the idea that 3 months of treatment is sufficient for the less severe tumors…. Finally, the French trial including 2022 patients showed that 6 months of Folfox (only 10% of patients treated with Xelox) were superior to 3 months of treatment….. At the end, it is not completely easy to give a conclusive advice that could be used in clinical practice. It has also to be kept in mind that the comparison between Xelox and Folfox was not the endpoint of these trials, even if it can be considered that in monotherapy capecitabine seemed to give better results that 5FU… At this stage, my recommendations would be to follow the results of the global analysis: 3 months of treatment for stage III “light” pT1-3N1, 6 months for pT4 or N2… And maybe it would be good to recommend a larger use of Xelox regimen.… We are waiting for new presentations of more complete data during ESMO Madrid 2017….
FOLFOX4/XELOX in stage II–III colon cancer: Efficacy results of the Italian three or six colon adjuvant (TOSCA) trial
Alberto F. Sobrero, Sara Lonardi, Gerardo Rosati, Maria Di Bartolomeo, Monica Ronzoni, Nicoletta Pella, et al.09/22/2017 - 10:25J Clin Oncol 35, 2017 (suppl; abstr 3501)
Three versus six months adjuvant oxaliplatin-based chemotherapy for patients with stage III colon cancer: The French participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project
Thierry Andre, Franck Bonnetain, Laurent Mineur, Jaafar Bennouna, Jérôme Desrame, Roger Faroux, et al.09/22/2017 - 10:07J Clin Oncol 35, 2017 (suppl; abstr 3500)
Prospective pooled analysis of six phase III trials investigating duration of adjuvant oxaliplatin-based therapy (3 vs 6 months) for patients with stage III colon cancer: The IDEA (International Duration Evaluation of Adjuvant chemotherapy) Collaboration
Qian Shi, Alberto F. Sobrero, Anthony Frank Shields, Takayuki Yoshino, James Paul, Julien Taieb, et al.09/22/2017 - 09:45J Clin Oncol 35, 2017 (suppl; abstr LBA1)