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SABCS 2021 | Final results from PALLAS: adjuvant palbociclib in HR+/HER2- early breast cancer

Michael Gnant, MD, Medical University of Vienna, Vienna, Austria, shares the final results from the randomized, Phase III PALLAS trial (NCT02513394). PALLAS investigated whether the addition of the CDK4/6 inhibitor, palbociclib, to adjuvant endocrine therapy improves outcomes over endocrine therapy alone in patients with hormone receptor-positive, HER2-negative early breast cancer. The addition of palbociclib did not improve survival endpoints in this patient population; whether the addition of CDK4/6 inhibition to particular subgroups of patients is being investigated. This interview took place at the San Antonio Breast Cancer Symposium 2021 in San Antonio.

Transcript (edited for clarity)

PALLAS is the adjuvant study on palbociclib in addition to standard endocrine treatment. The background for this was that obviously palbociclib as other CDK4/6 inhibitors yielded great benefits in terms of progression-free survival and even over survival in the metastatic breast cancer setting. So it was just logical to try to transfer these benefits to the curative setting in the adjuvant treatment...

PALLAS is the adjuvant study on palbociclib in addition to standard endocrine treatment. The background for this was that obviously palbociclib as other CDK4/6 inhibitors yielded great benefits in terms of progression-free survival and even over survival in the metastatic breast cancer setting. So it was just logical to try to transfer these benefits to the curative setting in the adjuvant treatment. Unfortunately, we were disappointed because overall the result of the PALLAS study is negative. That was already indicated by a futility interim analysis about a year ago. And now it was confirmed in the final analysis based on almost 5,800 patients. At the median follow up of 31 months we did not find the benefit for the addition of palbociclib. This is also true for all the subgroups and all the secondary endpoints. Logically, there was no difference for survival. This is disappointing and people discuss why is this trial negative.

Whereas in comparison, for example, MONARCH confirmed their 5% benefited at four years. And there is a number of reasons potentially explaining that. Number one could be that the risk distribution in these two trials is different. I don’t think that’s actually the reason because even the highest risk cohort within PALLAS doesn’t show signal. It could be that the drug exposure is different. I need to believe that, because PENELOPE also using palbociclib, also a negative trial had a much better drug exposure as compared to PALLAS. It could be that just the two drugs are different, which many consider unlikely given that they have almost similar PFS benefits in the metastatic setting. So what I personally believe makes the difference is the different scheduling. Palbociclib as ribociclib in the NATALEE trial that is forthcoming is given in a three weeks on one week off schedule. Whereas Abemaciclib is given continuously and particularly in the early breast cancer setting when we are not targeting proliferating metastasis, but we are trying to catch awakening, dormant cells so to speak. That might actually make a difference.

There is a huge translational program going on, we call it the TRANS-PALLAS. Which will try to investigate further reasons for failure or whether there would be a subgroup, either molecular defined or clinically defined with longer follow up where we can find a difference. And it’s going to be a huge resource. I mean after all, hundreds of caregivers in 21 countries collaborated in this role model trial. So despite a disappointing primary result, I consider this a great success.

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