Nationwide real-world practice pattern and clinical data of palbociclib in patients with HR(+), HER2(-) metastatic breast cancer (KCSG BR21–15)

Background: Introduction of cyclin-dependent kinase 4/6 inhibitors in hormone-receptor (HR) positive/human epidermal growth factor-2 (HER2) negative metastatic breast cancer (MBC) have dramatically improved clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS). Although PALOMA-2 trial has met its primary outcome, it showed relatively shorter OS compared to other pivotal phase III trials with ribociclib and abemaciclib. In Korea, there are limitations to use palbociclib + AI + GnRHa in premenopausal women, and bilateral salpingo-oophorectomy is necessary before starting palbocliclib based on unique approval status. We analyzed the real-world clinical outcome of letrozole + palbociclib, including distinct baseline characteristics in Korea. Methods: Between August 2016 to December 2022, 1,017 HR-positive, HER2 negative postmenopausal MBC patients treated with letrozole with palbociclib as first line treatment were enrolled from 21 tertiary institutions participating Korean Cancer Study Group (KCSG) breast cancer committee. Medical records were collected retrospectively. Primary endpoint was the PFS of letrozole + palbociclib in total patient population and the survival difference according to the method of menopause (natural menopause or bilateral salpingo-oophrectomy, BSO). The key secondary endpoint was OS, post-progression treatment pattern, overall response rate and safety. Results: Median age of the patient was 56 years (range 27~92), with median follow-up duration of 44.8 months (interquantile range 30.8~56.47). Among total patient population, 51 patients (5%) were below 40 years of age. Most patients diagnosed as recurrent breast cancer (633, 62.2%) received adjuvant tamoxifen +/- GnRHa (404, 73.5%). Median PFS and OS was 28.0 months (95% CI 25.53–32.10) and 61.6 months (95% CI 56.93–66.80). Patients who received BSO prior to palbociclib showed similar mPFS compared to natural menopause group (28.07 vs. 28.0 months) (P=0.35). Patients with primary -tamoxifen resistance showed inferior PFS compared to secondary resistance (mPFS 14.63 vs. 27.07 months, P=0.0059). ORR was 47.5% with DCR of 89.6%. Most patients experienced any grade of neutropenia (967 patients, 95.1%), 638 patients with grade 3 neutropenia (62.7%). Among 549 patients with progressive disease, 317 patients (58.1%) received second-line endocrine treatment, with everolimus + exemestane most used. In 204 patients (37.4%) who received cytotoxic chemotherapy, capecitabine was most frequently used (95, 17.3%). About 10% patients participated in clinical trials. Conclusions: To our knowledge, this is the largest country-based real-world data of 1^st line palbociclib in Asia. Palbociclib showed OS over 60 months, comparable to other pivotal clinical trials. Further follow-up analysis of PFS2 and subsequent treatment is warranted. Research Sponsor: Pfizer.