Palbociclib plus letrozole prolongs survival in Asian patients with advanced breast cancer

“PALOMA-4 is the largest phase III randomized study [assessing the efficacy and safety] of a cyclin-dependent kinase [CDK] 4/6 inhibitor as first-line treatment in Asian women with advanced ER-positive and HER2-negative BC to date,” said Dr Binghe Xu of the National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China. [Xu B, et al, ESMO 2021, abstract 228MO]

Results of the study showed a significant improvement in investigator- assessed PFS with palbociclib-letrozole vs placebo-letrozole (median, 21.5 months vs 13.9 months; hazard ratio [HR], 0.677; 95 percent confidence interval [Cl], 0.529 to 0.867; p=0.0012) at the data cut-off on 31 August 2021.

“The PFS improvement with palbociclib vs placebo among Asians demonstrated in PALOMA-4 was comparable to that observed in non-Asians, as shown in the PALOMA-2 study,” continued Xu.

“Subgroup analysis of PALOMA-4 showed a consistent PFS benefit with palbociclib vs placebo across prespecified subgroups, except for those aged ≥65 years [HR, 1.247; p=0.713]. The effect in the subgroup of patients aged ≥65 years could be limited by small sample size [14 patients in the palbociclib-letrozole arm vs 24 patients in the placebo-letrozole arm],” Xu continued.

The PALOMA-4 study enrolled 340 postmenopausal Asian patients (median age, 54.0 years; mainland Chinese, 83.8 percent; Eastern Cooperative Oncology Group [ECOG] performance status 0–1) with advanced ER-positive and HER2-negative BC who had not received previous systemic therapy for advanced disease. The patients were recruited from 52 centres across five Asian countries and regions. Prior neoadjuvant endocrine therapy (ET) was permitted. Enrolled patients were randomized (1:1) to receive palbociclib (125 mg/day, orally for 3 weeks followed by 1 week off over 28- day cycles) plus letrozole (2.5 mg/day) or placebo plus letrozole.

Overall, baseline characteristics were balanced between the treatment groups. Measurable disease was present in 85.8 percent vs 83.0 percent of patients in the palbociclib-letrozole vs placebo-letrozole group, with bone, lung and lymph nodes being the most common disease site involved. De novo metastasis was detected in 20.1 percent vs 18.7 percent of patients in the palbociclib-letrozole vs placebo- letrozole group.

Investigator-assessed objective response rate (ORR) and clinical benefit rate (CBR; complete response plus partial response) were comparable between the palbociclib-letrozole and placebo-letrozole groups (ORR: 37.3 percent vs 31.6 per- cent; odds ratio [OR], 1.3; 95 percent CI, 0.81 to 2.0; p=0.154) (CBR: 79.3 percent vs 80.1 percent; OR, 0.95; 95 percent CI, 0.53 to 1.7; p=0.471), with a higher ORR observed among those with measurable disease compared with the overall cohort (palbociclib-letrozole group: 43.4 percent vs 37.3 percent) (placebo-letrozole group: 38.0 percent vs 31.6 percent).

No new safety signals associated with palbociclib plus letrozole were identified. The adverse event (AE) profile of the combination therapy was consistent with that observed in the PALOMA-2 study. Febrile neutropenia occurred in 2.4 percent of patients in the palbociclib-letrozole arm. Treatment discontinuation due to AEs was required in 7.7 percent vs 2.9 percent of patients in the palbociclib- letrozole vs placebo-letrozole group, with neoplasm progression and pulmonary embolism being the most common AEs leading to treatment discontinuation in the palbociclib-letrozole arm. Serious AEs occurred in 15.5 percent vs 9.4 percent of patients in the palbociclib-letrozole vs placebo- letrozole group, with febrile neutropenia as a serious AE reported in one patient (0.6 percent) in the palbociclib-letrozole group.