Sibylle Loibl, MD, PhD, on Primary Results of the Randomized, Phase III PADMA Study in HER2-Negative/HR-Positive Metastatic Breast Cancer

The PADMA study investigated whether an endocrine-based treatment with palbociclib is superior to mono chemotherapy as first-line treatment in hormone receptor-positive HER2-negative metastatic breast cancer patients. And the study enrolled 130 patients, 120 did start the treatment. And with this we could demonstrate that actually, indeed the hypothesis was true and the time to treatment failure as an endpoint, which included not only progression and death, but also stopping the treatment due to toxicity and patient's preference, could be improved with the endocrine-based treatment from 7.2 month to 17 months around. This was really a great improvement with a hazard rate of 0.45, which is really great. And this was highly statistically significant and clinically meaningful. Of course, we looked at more conventionally timed events endpoints like the progression-free survival, where we saw actually the main difference in favor of the endocrine-based treatment with palbociclib and patients in the mono chemotherapy arm just were progression-free for about seven months. Almost identical results, and also we saw that the overall survival tended to be longer with about 10 months longer for the patients on endocrine-based treatment. One cannot say that the mono chemotherapy arm was inferior because it was capecitabine and paclitaxel which is really the standard of care as mono chemotherapy. But with that, I think now we have the second study reporting those data in the first line metastatic breast cancer and I think now it confirms that chemotherapy has no role in patients with hormone receptor-positive, HER2-negative breast cancer. The standard of care is and remains an endocrine-based treatment for now with a CDK 4/6 inhibitor, but others will come. We have seen the now 120 data with a triplet combination for those who have an additional PI3K kinase mutation, and I think those data are all very supportive that we really can treat patients irrespective of the type of mutations with an endocrine-based treatment. Toxicity wise, we saw not many differences. What we saw before, of course, palbociclib comes with a higher rate of hematologic toxicity. The non-hematologic toxicity was equal in both arms. And capecitabine, as we know, has the main issue with diarrhea and hand-foot syndrome, which was more common there. In conclusion, chemotherapy is out as first-line treatment in metastatic breast cancer for hormone receptor positive HER2-negative breast cancer patients.