This is globally the first randomized trial of a CDK 4/6 inhibitor in endometrial cancer. So the trial was done as double-blinded, Placebo-controlled and it was phase two trial and we used CDK 4/6 Palbociclib combined with Letrozole. Letrozole is more or less the standard of care in estrogen receptor-positive endometrial cancer and the patients were advanced or recurrent endometrial cancer patients...
This is globally the first randomized trial of a CDK 4/6 inhibitor in endometrial cancer. So the trial was done as double-blinded, Placebo-controlled and it was phase two trial and we used CDK 4/6 Palbociclib combined with Letrozole. Letrozole is more or less the standard of care in estrogen receptor-positive endometrial cancer and the patients were advanced or recurrent endometrial cancer patients. The trial was sponsored by the NSGO-Nordic Society of Gynaecological Oncology and we had seven European countries collaborating in this trial under umbrella of ENGOT that has me to Italy, Jayco, Spain and Mergo, Germany. And within the Nordic society, Denmark, Norway, and Sweden.
As you know that cyclin A is involved in transition of G1 to S phase and D2 to M phase and its activity can be inhibited by CDK 4/6 inhibitors like Palbociclib, which we used here and endometrial carcinomas are hormone-dependent and endocrine treatment with an aromatase inhibitor is well established.
So this is what we did. So we took the patients. The patient population was patients with measurable primary advanced or metastatic disease, the estrogen receptor-positive with good performance status and they must not have received any CDK 4/6 inhibitor before, they may have received prior endocrine therapy. But it seems like that very few patients had prior endocrine therapy in the trial. And patients were randomized to receive either Letrozole with Placebo for Palbociclib or Letrozole plus Palbociclib and treatment was given until progression of disease. Letrozole is given daily, Palbociclib is given every three weeks with one week off and three week on. And we had 77 patients in this study, which was what we needed to have. And if you look at the patient characteristics, and this is an old, old population, this is endometrial cancer so the median age was 67, 68 years.
And quite a lot of co-morbidity like hypertension in almost half of the patients, diabetes and these patients had multiple prior lines of therapy. When we look at the results and the trial was powered only to show the progression-free survival, and we reached the primary endpoint and progression-free survival was increased from three months, medium for Letrozole and Placebo to 8.3 months in Letrozole plus Palbociclib with a hazard ratio of 0.56.
If you look at the other efficacy endpoints, you’ll see the same trend. If you look at the disease control rate, it was increased from 38% to 64% at six months. If you look at the patients who did not had prior endocrine therapy, that was the majority of the patients, hazard ratio is again 0.55 and patients with relapsed disease that’s again, the highest population was a hazard ratio of 0.61. The drug Palbociclib arm was a little more toxic. One can say because of the bone marrow toxicity, there was a higher number of neutropenia anemia, but these were manageable. And with the dose reductions and with those pause and only 25% of Palbociclib versus 13% of Placebo was discontinued in the trial.
So all in all patient-reported outcomes did not show any deterioration by adding Palbociclib. So all in all, we have a positive trial, it’s a phase two randomized Placebo-controlled trial and it is the first globally first trial of a CDK 4/6 inhibitor as a randomized trial. And we have reached our goal and that merits that we can do phase three validation. So we are looking forward to start our phase three trial so that this drug can be approved, this combination can be approved in endometrial cancer. Remember endometrial cancer is a disease where after paclitaxel, carboplatin, and maybe immune therapy, once in the lifetime, there are not many other options left to treat these patients.
