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01-04-2019 | Breast Cancer | Review

Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials

Authors: Fausto Petrelli, Antonio Ghidini, Rebecca Pedersini, Mary Cabiddu, Karen Borgonovo, Maria Chiara Parati, Mara Ghilardi, Vito Amoroso, Alfredo Berruti, Sandro Barni

Published in: Breast Cancer Research and Treatment | Issue 3/2019

Abstract

Background

Several trials have demonstrated the benefit of anti-CDK4/6 inhibitors plus endocrine therapy in estrogen receptor-positive (ER+) advanced breast cancer (BC), in first or subsequent lines of therapy. However, due to the lack of direct/indirect comparisons, there are no data demonstrating the superiority of one drug over the other. We compared the effectiveness of palbociclib, ribociclib, and abemaciclib in advanced ER + BC via an indirect adjusted analysis.

Methods

We performed electronic searches in the PubMed, EMBASE, and Cochrane databases for prospective phase 3 randomized trials evaluating anti-CDK4/6 inhibitors plus endocrine agents. We compared the results with an adjusted indirect analysis of randomized-controlled trials. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR) and G3–4 toxicities occurring in ≥ 5% of patients.

Results

Six trials and six treatment arms including a total of 3743 participants, were included. For PFS and ORR analysis, the three agents were similar in both first- and second-line studies. All G3–4 toxicities were similar, with reduced risk of diarrhea for palbociclib versus abemaciclib (relative risk [RR] 0.13, 95% CI 0.02–0.92; P = 0.04) and of QTc prolongation for palbociclib versus ribociclib (RR 0.02, 95% CI 0–0.83; P = 0.03). Despite different inclusion criteria and length of follow-up, similar features were noticed among second-line studies with the exception of increased risk of anemia G3–4 and diarrhea G3–4 for abemaciclib.

Conclusions

Based on PFS and ORR results of this indirect meta-analysis, palbociclib, ribociclib, and abemaciclib are equally effective in either first- or second-line therapy for advanced ER + BC. They, however, ported different toxicity profiles.

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Slamon DJ, Neven P, Chia S et al (2018) Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol 36(24):2465–2472. https://doi.org/10.1200/JCO.2018.78.9909 CrossRefPubMed

Sledge GW, Toi M, Neven P et al (2017) MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35(25):2875–2884. https://doi.org/10.1200/JCO.2017.73.7585 CrossRefPubMed

Cristofanilli M, Turner NC, Bondarenko I et al (2016) Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phas. Lancet Oncol 17(4):425–439. https://doi.org/10.1016/S1470-2045(15)00613-0 CrossRef

Goetz MP, Toi M, Campone M et al (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 35(32):3638–3646. https://doi.org/10.1200/JCO.2017.75.6155 CrossRefPubMed

Finn RS, Martin M, Rugo HS et al (2016) Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 375(20):1925–1936. https://doi.org/10.1056/NEJMoa1607303 CrossRef

Hortobagyi GN, Stemmer SM, Burris HA et al (2016) Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 375(18):1738–1748. https://doi.org/10.1056/NEJMoa1609709 CrossRefPubMed

Turner NC, Slamon DJ, Ro J et al (2018) Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med.NEJMoa1810527. https://doi.org/10.1056/NEJMoa1810527 CrossRefPubMed

Chen P, Lee NV, Hu W et al (2016) Spectrum and degree of CDK drug interactions predicts clinical performance. Mol Cancer Ther 15(10):2273–2281. https://doi.org/10.1158/1535-7163.MCT-16-0300 CrossRefPubMed

Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12. https://doi.org/10.1016/0197-2456(95)00134-4 CrossRefPubMed

10.

Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50(6):683–691. https://doi.org/10.1016/S0895-4356(97)00049-8 CrossRef

11.

Durairaj C, Ruiz-Garcia A, Gauthier ER et al (2018) Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer. Anticancer Drugs 29(3):271–280. https://doi.org/10.1097/CAD.0000000000000589 CrossRefPubMedPubMedCentral

12.

Rugo HS, Diéras V, Gelmon KA et al (2018) Impact of palbociclib plus letrozole on patient-reported health-related quality of life: Results from the PALOMA-2 trial. Ann Oncol 29(4):888–894. https://doi.org/10.1093/annonc/mdy012 CrossRefPubMedPubMedCentral

13.

Verma S, O’Shaughnessy J, Burris HA et al (2018) Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2. Breast Cancer Res Treat 170(3):535–545. https://doi.org/10.1007/s10549-018-4769-z CrossRefPubMedPubMedCentral

14.

Kiefer C, Sturtz S, Bender R (2015) Indirect comparisons and network meta-analyses: estimation of effects in the absence of head-to-head trials—part 22 of a series on evaluation of scientific publications. Dtsch Ärzteblatt Int 112(47):803–808. https://doi.org/10.3238/arztebl.2015.0803 CrossRef

15.

Kish JK, Ward MA, Garofalo D et al (2018) Real-world evidence analysis of palbociclib prescribing patterns for patients with advanced/metastatic breast cancer treated in community oncology practice in the USA one year post approval. Breast Cancer Res 20(1):1–8. https://doi.org/10.1186/s13058-018-0958-2 CrossRef

16.

Stearns V, Brufsky AM, Verma S et al (2018) Expanded-access study of palbociclib in combination with letrozole for treatment of postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer. Clin Breast Cancer. https://doi.org/10.1016/j.clbc.2018.07.007 CrossRefPubMed

17.

Rugo HS, Turner NC, Finn RS et al (2018) Palbociclib plus endocrine therapy in older women with HR+/HER2: advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer 101:123–133. https://doi.org/10.1016/j.ejca.2018.05.017 CrossRefPubMed

18.

Knudsen ES, Hutcheson J, Vail P, Witkiewicz AK (2017) Biological specificity of CDK4/6 inhibitors:dose response relationship, in vivo signaling, and composite response signature. Oncotarget 8(27):43678–43691. https://doi.org/10.18632/oncotarget.18435 CrossRef

19.

Sonke GS, Hart LL, Campone M et al (2018) Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res Treat 167(3):659–669. https://doi.org/10.1007/s10549-017-4523-y CrossRefPubMed

20.

Zheng J, Amantea M, Wang D (2015) Effect of palbociclib concentration on heart rate-corrected QT interval in patients with cancer. Can Res 75:9 SUPPL. 1CrossRef

21.

Ribnikar D, Volovat SR, Cardoso F (2018) Targeting CDK4/6 pathways and beyond in breast cancer. Breast 8(43):8–17

Title: Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials
Authors: Fausto Petrelli
Antonio Ghidini
Rebecca Pedersini
Mary Cabiddu
Karen Borgonovo
Maria Chiara Parati
Mara Ghilardi
Vito Amoroso
Alfredo Berruti
Sandro Barni
Publication date: 01-04-2019
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Diarrhea
Diarrhea
Fulvestrant
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05133-y

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Abstract

Background

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