Tesetaxel Plus Reduced Dose Capecitabine for HR+ Metastatic Breast Cancer

PracticeUpdate: One of the major presentations looks at the use of an oral taxane drug in hormone receptor-positive breast cancer. Why is tesetaxel a unique chemotherapeutic agent?

Dr. Tolaney: At San Antonio this year, we also saw results from the CONTESSA Trial. This study examined a very novel oral taxane called tesetaxel. This agent has a very long half-life and in fact only needs to be dosed orally every three weeks.

And we've seen previous data from a single-arm Phase 2 trial that had looked at tesetaxel monotherapy and had demonstrated a response rate of 45% amongst patients with metastatic hormone receptor positive breast cancer. Given the very promising signal that was seen previously, the CONTESSA Study was designed to compare the addition of tesetaxel to low-dose capecitabine and to compare this combination to capecitabine monotherapy.

PracticeUpdate: What was the design of this study?

Dr. Tolaney: The trial enrolled patients with metastatic hormone receptor positive breast cancer. They could have received either zero or one prior lines of chemotherapy in the metastatic setting. Importantly, all of the patients were required to have had a prior adjuvant taxane. There was no pre-specified interval of time from receipt of prior adjuvant taxane to going on to this trial. The trial also allowed for prior CDK4/6 inhibition and did allow for patients with either measurable or valuable disease. The primary endpoint of the study was progression-free survival.

PracticeUpdate: What were some of the key findings?

Dr. Tolaney: The study found that the combination of tesetaxel and low-dose capecitabine was associated with a 9.8-month progression-free survival, and this was significantly better than the 6.9-month PFS seen with capecitabine alone. So this difference was consistent with a hazard ratio of 0.716 and was highly statistically significant with a p-value of .003. So the study did meet its primary endpoint. And importantly, when we looked at different subgroups, we could see that benefit was really seen across all subgroups, including patients who've had prior CDK4/6 inhibition, as well as patients who've had prior taxane regardless of the interval of time from their prior taxane.

To me, that's quite interesting, as one would think that patients who had had an adjuvant taxane not too long ago may not do as well with a reexposure to the taxane in the metastatic setting, but here you can see that with tesetaxel, they are benefiting similarly to those with long disease-free intervals.

There is also an improvement in objective response rates.

PracticeUpdate: What was the adverse effect profile of tesetaxel in this setting?

Dr. Tolaney: When we look at the toxicity profile of the combination, we can see that the combination was associated with more neutropenia compared to capecitabine alone. One thing I think that's important to keep in mind is certainly with taxane therapy in general, we worry about neuropathy, and in fact, rates of neuropathy with the tesetaxel treatment were quite low, with only about a 6% rate of grade 3-4 neurotoxicity seen in the combination arm.

Also, importantly, while we worry about alopecia in patients getting taxane therapy, in this trial, the rate of alopecia was actually very low, with grade 2 alopecia being experienced only by 8% of patients in the tesetaxel arm.

PracticeUpdate: How would you implement these data into your practice?

Dr. Tolaney: My takeaway message from this study is that the combination of tesetaxel and this reduced dose of capecitabine was superior to capecitabine, and the toxicity profile suggests low rates of alopecia and neurotoxicity with this novel taxane therapy. It's also very convenient, only given every three weeks.

I think the challenge with this study, however, is that it did use doublet chemotherapy. And I think many of us tend to have a preference for using single agent treatment. So there is more work ongoing that is further evaluating tesetaxel alone. This is being done in the CONTESSA TRIO study, and I think this will give us a more robust evaluation of efficacy with the monotherapy, but I think this does represent a very promising new oral taxane and that likely it will be incorporated into standard of care treatment.