Activity of CDK4/6 inhibitors and parameters affecting survival in elderly patients in age-subgroups: Turkish Oncology Group (TOG) retrospective study.
Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials. To contribute to the literature, we investigated the real-world efficacy, factors associated with survival and the rates of adverse events (AEs) of the treatment with palbociclib or ribociclib plus ET in the HR+/HER2- MBC patient cohort over the age of 65 for age subgroups. In this retrospective study, 348 patients were divided into subgroups: 65-69 years old, 70-79 years old and 80 years and older. Median PFS (mPFS) for whole group was 18.3 (95% CI,14.3-22.3) months. There was no significant difference in mPFS between age groups (p = 0.75). The estimated median OS (mOS) was 39.5 (95% CI, 24.9-54.1) months and there was no significant difference between age groups (p = 0.15). There was a meaningfull numerical difference that did not reach statistical significance in patients who received CDK4/6i treatment as the first line for MBC. Grade 3-4 AEs were reported in 42.7% for the entire group, and neutropenia was the most common (37.3%). It can be concluded that combination therapy with palbociclib or ribociclib with an ET partner has similar efficacy and is safe among subgroups of older patients diagnosed with HR+/HER2-MBC.
Kahraman S
，Hizal M
，Demirel BC
，Guven DC
，Gumusay O
，Uluc BO
，Bayram E
，Gulbagci B
，Yasar A
，Davarci SE
，Mocan EE
，Acar O
，Isik D
，Aydin E
，Karakas Y
，Ozcelik M
，Keser M
，Okutur SK
，Eren O
，Menekse S
，Aydin D
，Yilmaz F
，Dogan O
，Ozkanli G
，Yucel H
，Sunar V
，Aykan MB
，Ozdemir O
，Duman BB
，Keskinkilic M
，Sakalar T
，Inal A
，Karaoglanoglu M
，Aksoy A
，Er MM
，Turhal NS
，Kalkan NO
，Sendur MAN
... -
《BMC CANCER》
Comparative effectiveness analysis of survival with first-line palbociclib or ribociclib plus AI in HR + /HER2- advanced breast cancer (CEPRA study): preliminary analysis of real-world data from Thailand.
The current standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 -) advanced breast cancer (ABC) is a combination of aromatase inhibitor (AI) plus CDK4/6 inhibitors (CDK4/6i). Direct comparison trials of different CDK4/6i are scarce. This real-world study compared the effectiveness of first-line AI plus ribociclib versus palbociclib.
This multicenter retrospective cohort study, conducted in six cancer centers in Thailand, enrolled patients with HR + /HER2 - ABC treated with first-line AI, and either ribociclib or palbociclib. Propensity score matching (PSM) was performed. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), time to chemotherapy (TTC), and adverse events.
Of the 250 patients enrolled, 134 patients with ribociclib and 49 patients with palbociclib were captured after PSM. Baseline characteristics were well-balanced between groups. Median PFS in patients receiving ribociclib and palbociclib were 27.9 and 31.8 months, respectively (hazard ratio: 0.87; 0.55-1.37). The median OS in the AI + ribociclib arm was 48.7 months compared to 59.1 months in the AI + palbociclib arm (hazard ratio: 0.55; 0.29-1.05). The median TTC in the AI + palbociclib group was 56 months, but not reached in the AI + ribociclib group (p = 0.42). The ORR of AI + ribociclib and AI + palbociclib were comparable (40.5% vs. 53.6%, p = 0.29). Patients receiving palbociclib demonstrated a higher proportion of neutropenia compared to those receiving ribociclib, despite a similar dose reduction rate (p = 0.28). Hepatitis rate was similar between the ribociclib (21%) and palbociclib groups (22%). Additionally, a low incidence of QT prolongation was observed in both the ribociclib (5%) and palbociclib groups (4%).
This preliminary analysis of a real-world study demonstrated the comparable effectiveness of ribociclib and palbociclib with AI as an initial therapy for HR + /HER2 - ABC. No statistically significant difference in PFS, OS, and TTC was found in patients treated with AI combined with palbociclib or ribociclib. Longer follow-up and further prospective randomized head-to-head studies are warranted.
Dajsakdipon T
，Susiriwatananont T
，Wongkraisri C
，Ithimakin S
，Parinyanitikul N
，Supavavej A
，Dechaphunkul A
，Sunpaweravong P
，Neesanun S
，Akewanlop C
，Dejthevaporn T
，TSCO Breast Oncology Group
... -
《BMC CANCER》
Palbociclib plus endocrine therapy versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (Young-PEARL): overall survival analysis of a randomised, open-label, phase 2 study.
The phase 2 randomised Young-PEARL study demonstrated that palbociclib plus exemestane with ovarian function suppression significantly prolonged progression-free survival compared with capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Here, we report results of the protocol-specified secondary endpoint of overall survival.
Young-PEARL was a multicentre, randomised, open-label, phase 2 study conducted at 14 institutions in South Korea. Premenopausal women aged 19 years or older with histologically confirmed hormone receptor-positive, HER2-negative metastatic breast cancer that recurred or progressed during or after previous tamoxifen treatment, who were aromatase inhibitor naive, and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. One previous line of chemotherapy was permitted in the metastatic setting. Eligible patients were randomly assigned (1:1), using block randomisation (block size of two) stratified by previous chemotherapy for metastatic breast cancer and presence of visceral metastasis, to receive either palbociclib (orally, 125 mg per day on a 3-weeks-on, 1-week off schedule) plus exemestane (orally 25 mg daily) with leuprorelin (subcutaneously 3·75 mg on day 1 of each 28-day cycle) or capecitabine (orally, 1250 mg/m2 twice a day on a 2-weeks-on, 1-week-off schedule) until disease progression or unacceptable toxicity). The primary endpoint was progression-free survival. Overall survival was a secondary endpoint. All analyses were done in the modified intention-to-treat population (ie, included all patients randomly assigned to treatment who had at least one post-baseline CT scan and excluded those who did not receive study medication and who had any major violation of the eligible criteria). Safety was assessed in all patients who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02592746, and is now complete.
Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled. 184 patients were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92), of whom 174 were included in the modified intention-to-treat population (n=90 in the palbociclib plus endocrine therapy group and n=84 in the capecitabine group). All patients were female and ethnicity data were not collected. As of data cutoff (Feb 29, 2024), median follow-up was 54·0 months (IQR 34·1-74·4). Median progression-free survival was 19·5 months (90% CI 14·3-22·2) for palbociclib plus endocrine therapy and 14·0 months (11·7-18·7) for capecitabine (hazard ratio 0·74 [90% CI 0·57-0·98]; one-sided log-rank p=0·036). 52 (58%) of 90 patients in the palbociclib plus endocrine therapy group and 48 (57%) of 84 in the capecitabine group died, with a median overall survival of 54·8 months (95% CI 48·9-77·1) in the palbociclib plus endocrine therapy group versus 57·8 months (46·3-89·2) in the capecitabine group (hazard ratio 1·02 [95% CI 0·69-1·51]; p=0·92). The most common grade 3 or worse adverse event was neutropenia (59 [64%] of 92 in the palbociclib plus endocrine therapy group vs 15 [18%] of 85 in the capecitabine group) . No treatment-related deaths occurred.
With extended follow-up, palbociclib plus exemestane with ovarian function suppression continued to show a significant benefit in progression-free survival compared with capecitabine in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had been previously treated with tamoxifen; however, no improvement in overall survival was seen. Given the progression-free survival benefit, the upfront use of palbociclib plus endocrine therapy is the preferred option for premenopausal women, although a capecitabine-first strategy might be an alternative treatment strategy for maintaining overall survival in resource-limited settings.
Pfizer and Ministry of Health & Welfare, South Korea.
Ahn HK
，Kim JY
，Lee KH
，Kim GM
，Kang SY
，Lee KS
，Kim JH
，Lee KE
，Lee MH
，Kim HJ
，Kim HJ
，Koh SJ
，Park IH
，Sohn J
，Kim SB
，Ahn JS
，Kim S
，Cho H
，Jung KH
，Im SA
，Park YH
，Korean Cancer Study Group (KCSG) Breast Cancer Committee
... -
《-》
ResearchGate
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钛学术
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