Editor's Note: In the journey of cancer treatment, chemotherapy acts as a double-edged sword, bringing hope for survival to patients while also accompanying a series of adverse reactions, among which the treatment of refractory nausea caused by chemotherapy is particularly challenging. At the 47th SABCS conference, Professor Luke Peppone from the University of Rochester Medical Center, Rochester, New York, introduced the results of the URCC 16070 study (Abstract No.: RF2-06), a nationwide, double-blind, Phase III randomized controlled trial focusing on the efficacy comparison between olanzapine and prochlorperazine in treating refractory nausea caused by chemotherapy. Oncology Frontier specially interviewed Professor Luke Peppone at the SABCS conference, inviting him to elaborate on the original intent and design of the study and to conduct an in-depth analysis of the results and their clinical significance. He pointed out that although existing drugs perform well in controlling vomiting, the control of nausea still needs further optimization. Through this study, we hope to provide clinicians with new treatment options to improve patients' quality of life.Oncology Frontier：Could you tell us about the original intention of conducting this URCC 16070 phase III randomized controlled trial? Why choose olanzapine and prochlorperazine as agents for nausea caused by refractory chemotherapy?
Professor Luke Peppone: So yeah, a lot of breast cancer patients undergoing chemotherapy will have nausea and vomiting. The drugs that we provide now are excellent at controlling vomiting with over 90% reduction. However, the control of nausea is less than that, around 50%. And that’s because it’s just a harder target for pharmaceuticals to hit , where vomiting is really one center in the brain, nausea is spread to a bunch. So they still have nausea despite a reduction in vomiting, which is quite unpleasant, as you can imagine. So we had two drugs, which were approved in the United States many, many years ago. And we have significant experience with these drugs. So we know their safety profile, they are definitely relatively safe, in terms of pharmaceuticals. And they are relatively cheap for our population and plentiful. They’re available and generic. So it’s very easy to get that. And that was sort of reason why we did this study.
Oncology Frontier：According to the results of the study, olanzapine was significantly superior to placebo in reducing nausea and improving quality of life, but did not show superiority over prochlorperazine. How do you interpret this result? Does this mean that olanzapine is more appropriate as the first choice for the treatment of refractory chemotherapy-induced nausea?
Professor Luke Peppone:Yeah, that’s a great question. Our results did show that olanzapine reduced nausea slightly more than prochlorperazine. And also, olanzapine resulted in an improvement of quality of life, where prochlorperazine did not. So it’s a tough question, but it’s a question that clinicians would have to answer for themselves. I would say olanzapine is probably the best choice. But I would also say that prochlorperazine is also a good choice. You might find that a patient is too sedated on olanzapine, so they might want to try prochlorperazine or vice versa. I think they’re both very good options for refractory nausea and chemotherapy patients, with olanzapine potentially being a slightly better choice and perhaps the first choice, but up to each clinician.
Oncology Frontier：What was the safety profile of olanzapine and prochlorperazine in this study? Did any patients have serious adverse effects or need to discontinue the drug? What patient factors do you think need to be considered to ensure safety and tolerability when selecting this class of drugs?
Professor Luke Peppone:So in terms of safety profile, both of those drugs were excellent, and we had no serious adverse events related to the study intervention drugs, either olanzapine or prochlorperazine. We had a number of adverse events that were all expected. Olanzapine is known to cause sedation and some drowsiness, and those were the typical adverse events that we dealt with, similar with prochlorperazine, but nothing unexpected. And adverse events between the placebo and the study interventions were very similar. We’re still teasing apart those, but the safety profile of those two drugs in our study and in previous research are excellent, and that’s one of the many reasons why they were chosen, and we like using these drugs in these patients.
Oncology Frontier：Based on the results of this study, how would you personalize your antiemetic regimen in your clinical practice? How will the results of this study affect your clinical practice decisions?
Professor Luke Peppone: Yeah, so I myself am a PhD, and I really don’t treat patients. However, I have a number of very close colleagues that treat their patients. Our university at the University of Rochester Medical Center has a long history in the nausea and vomiting realm due to chemotherapy, and we have used prochlorperazine for many years to control refractory nausea, and I will say in light of this study, more of our clinicians are moving towards olanzapine, and they’re having good results. Patients are saying that they are having significant reductions in nausea, so you can see that our clinical practice has slowly started changing where we are, and hopefully this trickles out to the rest of the population.
