The addition of palbociclib to letrozole resulted in prolonged progression-free survival (PFS) and a higher disease control rate (DCR) compared with placebo plus letrozole among patients with estrogen receptor (ER)–positive advanced endometrial cancer, according to results of a phase 2 trial presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.
“ENGOT-EN3/NSGO-PALEO is the first randomized trial to evaluate the efficacy of a CDK4/6 inhibitor in combination with an aromatase inhibitor in patients with advanced or recurrent ER-positive endometrial cancer,” Mansoor Raza Mirza, MD, of the Rigshospitalet Cophenhagen University Hospital in Denmark, and presenter of the study, said.
In the phase 2 ENGOT-EN3/NSGO-PALEO trial, 77 patients with stage 4 or relapsed ER-positive endometrial cancer were randomly assigned to receive palbociclib plus letrozole or placebo plus letrozole. The primary endpoint was PFS and the secondary endpoint was DCR.
The baseline characteristics were well balanced, with a median patient age of 68 years. Comorbidities were common; 41% of patients had hypertension and 13% had diabetes. Most patient received at least 1 prior line of therapy.
PFS was significantly longer with the combination of palbociclib plus letrozole, with a median of 8.3 months, compared with 3 months in the placebo arm (hazard ratio, 0.56; 95% CI, 0.32-0.98; P =.0376).
Domenica Lorusso, MD, PhD, of the Fondazione IRCCS National Cancer Institute of Milan in Italy, the invited discussant of the trial, noted that a subgroup analysis demonstrated no significant difference in PFS among patients with relapsed or progesterone receptor–positive disease — but the trial was not powered for efficacy of subgroup analyses.
DCR was also higher at 63.6% in the combination arm compared with 37.8% in the placebo arm.
Although overall quality of life scores were similar between the groups, adverse events (AEs) such as neutropenia, anemia, leucopenia, pain, and hypertension were more common in the combination arm. AEs led to dose reduction among 36% of patients who received palbociclib plus letrozole compared with 3% who received placebo and letrozole. Discontinuation of palbociclib or placebo occurred in 25% and 14% of patients, respectively, and letrozole was discontinued by 19% in the combination arm and 11% in the placebo arm.
Dr Mirza concluded that “compared with placebo plus letrozole, the combination of palbociclib plus letrozole demonstrated clinically meaningful improvement in PFS” and “the toxicity of palbociclib plus letrozole combination therapy was manageable.”
Dr Mirza said that these results warrant a phase 3 trial for further validation.
Disclosure: Some of the study presenters disclosed financial relationships with pharmaceutical companies. For a full list of disclosures, please refer to the original abstract.
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Mirza MR, Bjørge L, Marmé F, et al. A randomised double-blind placebo-controlled phase II trial of palbociclib combined with letrozole (L) in patients (pts) with oestrogen receptorpositive (ER+) advanced/recurrent endometrial cancer (EC): NSGO-PALEO/ENGOT-EN3 trial. Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA28.