Presentation on theme: "Does the Chemo Backbone Matter?"— Presentation transcript:
1Does the Chemo Backbone Matter? Wells Messersmith, MD, FACPProfessorDirector, Gastrointestinal Medical Oncology ProgramCo-Head, Division of Medical OncologyProgram co-Leader, Developmental TherapeuticsMarch 2014
2Conflict of Interest:No employment, speaker’s bureaus, stock ownership, royalties, patents, etcData Safety Monitoring Board for OncoMed3. PI or Local PI of clinical trials by Genentech/Roche, GSK, Pfizer, Millenium, Bayer, Onconova, and NIH/CTEP.
5CAIRO2: did not confirm- Worse outcomes (PFS and strong trend in OS) when “double biologics” are used.- Unexpected, and still mostly unexplained, result which shows why randomized trials are needed.Tol, NEJM 2009
6The dangers of cross-trial comparisons Lining up trials side by side, and drawing conclusions based on patterns that are seen, represents good scholarship and can generate important hypotheses.However, there are known and unknown factors with various studies: different countries, standards, tolerance, etcWhenever possible, randomized studies are needed to actually change practice
9CELIM study: No difference between chemo backbones This was a randomized phase II study with RR as primary endpointHowever, no difference is response or survival based on chemo backbone.FOLFIRI/CetxFOLFOX/CetxFolprecht, ASCO 2012
10CECOG: Cetuximab + FOLFOX v FOLFIRI Ocverk, World J GI 2010
11CECOG: No difference between chemo backbones This was a randomized phase II study with PFS at 9m as primary endpoint.Again, no difference in response or survival based on chemo backbone.Ocverk, World J GI 2010
12TRIBE Trial: Addition of Oxaliplatin Falcone, ASCO 2013
13Adding Oxaliplatin to Backbone Primary endpoint of PFS was met!Falcone, ASCO 2013
15Randomized Trials for chemo “backbones: CELIM trial - Cetuximab + FOLFOX vs. FOLFIRICECOG trialTRIBE- Bevacizumab + FOLFIRI vs FOLFOXIRIZero for three in terms of showing any specific detriment or advantage to thechemo backbone!
22Conclusions (1)Head-to-head randomized studies show no difference in terms of which chemo backbone is paired with biologics.Many of these are phase IIFor bevacizumab, large clinical databases show no difference.Cross-trial comparisons are complicated and can lead us down the wrong path (think of all of the patients treated with double biologics from ).Until we know biomarkers (with positive predictive value) for biologics, difficult to assess and model whether specific chemotherapies modify them.
23Conclusions (2)Unclear whether investment of increasingly precious resources (patients, $$$, time) is worthwhile.Study design: “rum and coke” v. “rum and pepsi”Overlapping toxicities and PK issues usually more relevant.The number of possible agents and combinations allow plenty of flexibility for oncologists uncomfortable with specific combinations.Would be better to dedicate resources to prevention, novel agents, and patient subsets/personalized medicine.
24Ongoing “Chemo Backbone” Trials MAVERICC (NCT ), n=360, randomized pIIFOLFIRI/bev vs FOLFOX/bevPLANET (NCT ), n=80, pIIFOLFIRI/Pmab vs FOLFOX/PmabVISNU-1 (NCT ), n=350, pIIIFOLFOXIRI/bev vs FOLFOX/bevCELIM2 (NCT ), n=256, pIIFOLFOXIRI vs FOLFIRI + Bev (KRAS MT) or Cetuximab (KRAS WT)