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Medicine Matters oncology

Hi, everyone. I'm here to talk about EA1131, which is a phase III randomized trial in patients with triple negative cancer with residual disease after completion of neoadjuvant chemotherapy that got randomized to either a platinum agent or a capecitabine. The rationale behind the study was that we believe that patients with triple negative cancer that has basal-like subtype, the platinum agent in the adjuvant setting would perform better from an invasive disease free survival point of view than capecitabine.



Unfortunately, after 410 patients were accrued with the fifth interim analysis of the trial, the DFMC recommended interrupting the trial, since it would be unlikely that platinum agents would be either superior or non-inferior to capecitabine in this high-risk patient population. Furthermore, more severe ray 3 and 4 toxicities were seen with platinum agents.



Also, we observe that the invasive disease-free survival at three years, as well as the recurrence-free survival and overall survival at three were substantially lower than had been seen in other clinical trials, which hovered about 45% for both platinum agents and capecitabine in patients with triple negative cancer, basal type subtype, and residual disease after completion of chemotherapy.



The rationale behind this is that these patients had to have more than one centimeter of disease in the surgical specimen. And therefore, from a residual cancer burden, had a residual cancer burden of either 2 or 3, which is also much higher than what has been seen in previous trials, such as CREATE- X.



Therefore, the take home message about this clinical trial is that A, platinum agents are not superior or non-inferior to capecitabine as adjuvant treatment for patients at high risk for recurrence with residual disease post-completion of neoadjuvant treatment, B, capecitabine remains the standard of care, despite the fact that the overall invasive disease-free survival is much lower than previously observed in other clinical trials, and C, much better treatments in the adjuvant setting are sorely needed, and EA1131 has a rich depth of correlatives that will hopefully indicate which types of clinical trials we should be focusing on in the future.



So probably the thing is obviously this trial has not looked at this, and the immunotherapy clinical trials so far do not-- like, the ones that have been reported up to this point, and we have not seen the data with KEYNOTE-522 yet presented. We know that from a press release the event-free survival a short follow up seems promising. But, what really will be needed is much longer follow up to know if overall survival is actually impacted.



And the rationale behind this statement is immunotherapy has very long term permanent side effects. Granted, they're not very common. But when they happen, they can be quite life changing and they are not fixable. Therefore, we will need to know if patients are going to live longer because of immunotherapy in terms of protecting them from a recurrence of cancer, but not killing them from immune toxicities then not.



So immunotherapy up to this point, is intriguing, it's important to help patients get the bigger shrinkage of their cancer, but it is unclear if this is for everyone. And potentially, I would recommend that if immunotherapy ends up being approved, it should be confined to patients at extremely high risk for recurrence, and it may not be for everyone.