PracticeUpdate Oncology February 2019

CONFERENCE COVERAGE 28

Dr. Haffizulla: You’re an author on one of the very big presentations this year in the conference, featuring additional results from the TAILORx. Can you remind us about the TAILORx trial and what it’s designed to evaluate, and tease forward some findings perhaps from this trial? Dr. Badve: The TAILORx trial essentially started in principle in 2002 where the whole idea was, "Can we find novel tools to iden- tify patients who are at risk and can these tools be used to identify patients in whom we can decrease the amount of chemother- apy?" So, as you remember, in 2001, any patient with node-positive disease or [was] relatively high risk received chemotherapy. The Oncotype DX assay was principally responsible for changing some of the prac- tices when the B14 and the B20 data came out, showing that the low-risk populations do phenomenally well and the high-risk populations have significant risk meriting aggressive therapy. The main question that remained is "What happens in the inter- mediate-risk score?" So with that in mind, the TAILORx trial was designed to iden- tify the risk of these patients and whether these patients get additional benefit from chemotherapy. The design essentially was to enroll patients with intermediate risk scores, randomize them, and see the influence of chemother- apy in their final outcome. So, the main trial consisted of 7000-plus patients with inter- mediate scores, but as the trial entry point, you could come in with the score or you could get the score done as a part of the trial. We also had 1000 patients who were in the low-risk and a similar number in the high-risk, so those were registered and those were also followed up to a limited extent. The main reasons of the trial, as pre- sented at ASCO this year, assured that in the intermediate group, defined as 11 to 25, chemotherapy had very minimal, if any, ben- efit for those patients. This, clearly, is great news for patients because there’s a large Race, Ethnicity, and Clinical Outcomes From the TAILORx Trial Interview with Sunil S. Badve MD, FRCPath by Farzanna S. Haffizulla MD, FACP, FAMWA

" …clinicians have to take into consideration, the impact of race and ethnicity. We clearly don’t know how they impact… But the simplest thing is making sure that the patient is aware of the data risk and monitoring them adequately is clearly what’s going to be important. "

be that the low-risk patients are doing sowell that to see an influence of race we might need thousands of patients and that study may not be powered to identify those differ- ences and maybe similar things might exist within the high risk category. So, the question basically is now, "Is chemotherapy benefi- cial by race?" And the answer is an emphatic no; that all patients that similarly end up in chemotherapy, it didn’t add any benefit in the intermediate group irrespective of race. But irrespective of the kind of clinical patho- logic parameters race remained an important parameter of a low-risk prognosis. So, we really need to understand what is the basis, the biological basis of the poor prognosis associated with race. Dr. Haffizulla: How did these findings com- pare to previously reported findings? Dr. Badve: They more or less fall in line. So, there have been prior studies in ran- domized clinical trials. The E1199 study, which was a Taxol/Taxotere-based study also had shown similar differences in black populations having a significantly worse outcome than the non-black populations. One surprise in this particular trial was the

population of patients that can now safely avoid chemotherapy andwe have now level I evidence to suggest that this is what one can do. A lot of people had a gut feeling that we could do that, but having the evi- dence makes people confident that they were doing the right thing. Now, the next question of course is “Are there subpopulations within them where you can see a degree of benefit, which is larger or significantly lower than other pop- ulations?” And the obvious question is “Is there an influence of race and ethnicity?” We often blame the influence of race on poor quality of health care, socioeconomic status and those kinds of thing. So this trial where everybody received more or less a similar therapy was a wonderful cohort to analyze the influence of race. And ana- lyzing the groups by race clearly showed that the black population had a significantly higher risk than any other population. And this is predominantly seen in the intermedi- ate group population where we had more than 7000 patients. Now, why we do not see it in the low-risk or in the high-risk is not quite clear, but it could

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