David J. Kerr, MD

Disclosures

May 24, 2012

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Hi. I am David Kerr, Professor of Cancer Medicine at the University of Oxford in the United Kingdom.

It's that time of year again, when all of us look forward to the American Society of Clinical Oncology (ASCO®) meeting, having our batteries recharged and returning reinvigorated, we hope, with practice-changing new trials, new information, and something that will make a difference to the patients that we look after. It is not a bad year for gastrointestinal cancer. In colorectal cancer and in advanced disease, at last we will have the answer to whether we should continue bevacizumab following progression through first-line chemotherapy. Two randomized trials will help us out there.[1,2]

We will also have some clarity on the role of aflibercept, an interesting novel vascular endothelial growth factor inhibitor (VEGF Trap), which is showing survival advantages in second-line treatment in combination with FOLFIRI [leucovorin, fluorouracil, irinotecan].[3] It is an interesting question as to whether we should use aflibercept or continue use of bevacizumab. At some stage, we will need head-to-head trials to sort out this dilemma.

At the other end of the spectrum are patients with refractory disease, who have progressed through all conventional treatments (first- and second-line chemotherapy, bevacizumab, and cetuximab). We have an interesting trial looking at the combination of capecitabine and an AKT inhibitor (perifosine) vs capecitabine alone.[4] Another randomized trial looked at the oral multikinase inhibitor regorafenib and its role in exactly the same position.[5] We suspect that both of these agents will add some value in terms of improving overall survival. That space is becoming clinically crowded in terms of the different options that we may have in third-line chemotherapy.

In terms of stomach and esophageal gastric cancer, there are some interesting trials coming forward. REAL3 looks at the combination of epirubicin, oxaliplatin, and capecitabine with or without panitumumab.[6] There will be an Intergroup report looking at the adjuvant chemotherapy comparators of conventional 5-fluorouracil leucovorin vs a much more complex dose-intense regime looking at irinotecan and 5-fluorouracil leucovorin, followed sequentially by docetaxel and cisplatin.[7] It will be interesting to see those results.

In hepatocellular cancer, at last it looks as if we are seeing some therapeutic benefits coming from inhibition of the MET pathway. MET is a tyrosine kinase receptor for hepatocyte growth factor, long believed to play an important, if not pivotal, role in maintaining the proliferative advantage of hepatocellular carcinoma cells. In a randomized phase 2 study of tivantinib, there may be some survival advantages in patients who have progressed through sorafenib.[8] We will also be seeing a phase 2 trial result of a drug that is an inhibitor of both MET and VEGFR2.[9] This drug is cabozantinib, and we will see some interesting phase 2 data there suggesting some activity. Things are heating up in hepatocellular carcinoma.

I am looking forward to the meeting; it is a great place to visit. I like to be invigorated with new, important data. Friends, colleagues, and peers come together as a community to share knowledge, as Ralph Waldo Emerson would say. I look forward to seeing you there.

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